Immune-Evasion Target Atlas
However a tumor evades the immune system, the question for your research is the same: can you see it in the tissue? Explore the immuno-oncology (IO) target landscape, then build the IHC/IF workflow to detect it.
How to read this: Every target maps to a detection workflow. Badges open the matching Vector IHC/IF and glycobiology solutions. Glyco flags targets where glycosylation changes your detection strategy. More detail provides the target’s IO relevance and associated post-translational modifications (PTMs). Stuck on workflow design? Ask a workflow expert or learn more about Vector Laboratories’ immuno-oncology solutions.
Myeloma antigen; SLAMF7 axis supports NK activation/phagocytic recognition (camouflage)
IO Relevance / Indications: Myeloma antigen; elotuzumab and ADC programs.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
'Don't-eat-me' signal; blocks phagocytic antigen uptake by APCs
IO Relevance / Indications: Anti-phagocytic signal via SIRPa; magrolimab and SIRPa-Fc agents restore phagocytosis.
Key PTMs / Glycobiology: N-terminal pyroglutamate (QPCTL) required for SIRPa binding; N-glycosylated
Phagocyte receptor for CD47 (innate phagocytosis checkpoint)
IO Relevance / Indications: Receptor for CD47 on phagocytes; targeted by SIRPa-Fc fusions (evorpacept, TTI-622).
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Impairs phagocytic antigen uptake (also exerts coercive suppression)
IO Relevance / Indications: Immunosuppressive ligand stabilized by glycosylation; ADC programs also emerging.
Key PTMs / Glycobiology: N-glycosylated; stabilizes surface B7-H4
APC-licensing agonist that restores antigen presentation/priming (counters camouflage)
IO Relevance / Indications: APC-activating TNFR; agonists license dendritic cells to prime anti-tumor T cells.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
CAF marker; FAP-driven stroma enforces immune exclusion (camouflage) – here a radioligand target
IO Relevance / Indications: Cancer-associated fibroblast marker; FAPI PET/therapeutic radioligands (pan-tumor).
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Cleaves heparan sulfate, remodeling immune-excluding stroma (camouflage).
IO Relevance / Indications: Cleaves heparan sulfate, remodeling immune-excluding stroma (camouflage).
Key PTMs / Glycobiology: ECM glyco-remodeler (heparan sulfate)
Non-classical MHC-Ib checkpoint engaging LILRB1/2; hides cells from T/NK (anti-HLA-G e.g. TTX-080).
IO Relevance / Indications: Non-classical MHC-Ib checkpoint engaging LILRB1/2; hides cells from T/NK (anti-HLA-G e.g. TTX-080).
Key PTMs / Glycobiology: N-glycosylated MHC-Ib; soluble isoforms (sHLA-G)
Ligand for NKG2A; cloaks cells from NK/CD8 surveillance (complements NKG2A blockade).
IO Relevance / Indications: Ligand for NKG2A; cloaks cells from NK/CD8 surveillance (complements NKG2A blockade).
Key PTMs / Glycobiology: N-glycosylated MHC-Ib; B2M-associated
Innate 'don't-eat-me' signal via Siglec-10; blocks macrophage phagocytosis (anti-CD24 programs).
IO Relevance / Indications: Innate 'don't-eat-me' signal via Siglec-10; blocks macrophage phagocytosis (anti-CD24 programs).
Key PTMs / Glycobiology: GPI-anchored, heavily O-/N-glycosylated and sialylated (Siglec-10 ligand)
Macrophage receptor for CD24 enforcing phagocytosis evasion.
IO Relevance / Indications: Macrophage receptor for CD24 enforcing phagocytosis evasion.
Key PTMs / Glycobiology: Sialoglycan-binding lectin (CD24 receptor)
Degrades surface MHC-I; inhibition restores antigen presentation (repurposed evolocumab/alirocumab).
IO Relevance / Indications: Degrades surface MHC-I; inhibition restores antigen presentation (repurposed evolocumab/alirocumab).
Key PTMs / Glycobiology: Autocatalytic zymogen maturation; secreted; N-glycosylated
Pyroglutamylates CD47 N-terminus enabling SIRPa binding; inhibition unblocks phagocytosis.
IO Relevance / Indications: Pyroglutamylates CD47 N-terminus enabling SIRPa binding; inhibition unblocks phagocytosis.
Key PTMs / Glycobiology: Glutaminyl cyclase installing CD47 N-term pyroglutamate (PTM writer)
NKG2D ligand; proteolytic shedding evades NK recognition (shedding-blocking Abs e.g. 7C6).
IO Relevance / Indications: NKG2D ligand; proteolytic shedding evades NK recognition (shedding-blocking Abs e.g. 7C6).
Key PTMs / Glycobiology: Proteolytically shed by ADAM10/17 + ERp5 (key evasion event)
NKG2D ligand lost via shedding; restoring surface display re-enables NK killing.
IO Relevance / Indications: NKG2D ligand lost via shedding; restoring surface display re-enables NK killing.
Key PTMs / Glycobiology: Proteolytically shed (ADAM10/17); soluble MICB blunts NKG2D
Sheddase cleaving MICA/B and other ligands; inhibition preserves NKG2D recognition.
IO Relevance / Indications: Sheddase cleaving MICA/B and other ligands; inhibition preserves NKG2D recognition.
Key PTMs / Glycobiology: Sheddase 'writer'; regulated by iRhom2 and phosphorylation
ER aminopeptidase shaping the MHC-I immunopeptidome; modulation alters neoantigen display.
IO Relevance / Indications: ER aminopeptidase shaping the MHC-I immunopeptidome; modulation alters neoantigen display.
Key PTMs / Glycobiology: Regulated by phosphorylation / ubiquitination
Collagen cross-linker stiffening stroma to physically exclude T cells.
IO Relevance / Indications: Collagen cross-linker stiffening stroma to physically exclude T cells.
Key PTMs / Glycobiology: Secreted; N-glycosylated
Collagen receptor aligning matrix into a T-cell-excluding barrier.
IO Relevance / Indications: Collagen receptor aligning matrix into a T-cell-excluding barrier.
Key PTMs / Glycobiology: Receptor tyrosine kinase: ligand-induced autophosphorylation; N-glycosylated ECD
Drives immunosuppressive angiogenesis and blocks DC maturation/T-cell infiltration (bevacizumab).
IO Relevance / Indications: Drives immunosuppressive angiogenesis and blocks DC maturation/T-cell infiltration (bevacizumab).
Key PTMs / Glycobiology: Secreted, glycosylated; heparin-binding isoforms
Innate DNA-sensing hub; agonists restore tumor recognition (counter-camouflage).
IO Relevance / Indications: Innate DNA-sensing hub; agonists restore tumor recognition (counter-camouflage).
Key PTMs / Glycobiology: Palmitoylation (Cys88/91) required for activation; TBK1 phosphorylation; ubiquitination
Mismatch-repair deficiency raising neoantigen burden; tumor-agnostic ICI biomarker (recognition).
IO Relevance / Indications: Mismatch-repair deficiency raising neoantigen burden; tumor-agnostic ICI biomarker (recognition).
Key PTMs / Glycobiology: N/A (composite biomarker)
Loss abolishes surface MHC-I -> antigen-presentation failure and ICI resistance (camouflage).
IO Relevance / Indications: Loss abolishes surface MHC-I -> antigen-presentation failure and ICI resistance (camouflage).
Key PTMs / Glycobiology: Small non-glycosylated chain; serum-soluble
MHC-I expression/genotype incl. LOH; gates neoantigen recognition.
IO Relevance / Indications: MHC-I expression/genotype incl. LOH; gates neoantigen recognition.
Key PTMs / Glycobiology: N-glycosylated MHC-I; B2M-associated
Antigen-presentation/activation status of APCs and T cells.
IO Relevance / Indications: Antigen-presentation/activation status of APCs and T cells.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Myofibroblastic CAF density marking immune-excluded stroma (camouflage).
IO Relevance / Indications: Myofibroblastic CAF density marking immune-excluded stroma (camouflage).
Key PTMs / Glycobiology: Regulated by phosphorylation / ubiquitination
Hydrolyzes ATP→AMP; impairs APC recruitment and seeds adenosine-driven effector suppression
IO Relevance / Indications: Hydrolyzes ATP to AMP; drives immunosuppressive adenosine in TME.
Key PTMs / Glycobiology: N-glycosylated ecto-ATPase (CD39)
Generates immunosuppressive adenosine; impairs recruitment and effector function
IO Relevance / Indications: Generates adenosine from AMP; oleclumab; key TME immunosuppression and ICI resistance.
Key PTMs / Glycobiology: GPI-anchored ecto-5'-nucleotidase; N-glycosylated; shed soluble CD73
Surface docking of latent TGF-beta on Tregs/platelets; localizes immunosuppression.
IO Relevance / Indications: Surface docking of latent TGF-beta on Tregs/platelets; localizes immunosuppression.
Key PTMs / Glycobiology: Disulfide-tethers latent TGF-beta (proLAP); N-glycosylated (GARP)
Antigen-directed modality; biology intersects coercion via Treg depletion
IO Relevance / Indications: Treg/leukemia marker; ADCs and Treg-depleting antibodies.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
T-cell co-inhibitory receptor; blockade restores effector activation
IO Relevance / Indications: Primary T-cell co-inhibitory receptor; anti-PD-1 (pembrolizumab, nivolumab) is foundational ICI therapy across many tumor types.
Key PTMs / Glycobiology: N-glycosylated ECD; glycosylation tunes PD-1/PD-L1 blockade
Tumor co-inhibitory ligand engaging PD-1 on T cells
IO Relevance / Indications: Ligand for PD-1 on tumor/immune cells; key biomarker and target (atezolizumab, durvalumab); drives 'coercion' immune evasion.
Key PTMs / Glycobiology: Heavily N-glycosylated (stabilizes PD-L1, blocks degradation, masks epitopes) + palmitoylated; glyco-PD-L1 itself an Ab target
Secondary PD-1 ligand reinforcing T-cell suppression
IO Relevance / Indications: Second PD-1 ligand contributing to T-cell suppression; relevant to PD-1 pathway resistance.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Dampens T-cell priming/activation; relieves Treg-mediated brake
IO Relevance / Indications: Co-inhibitory receptor limiting T-cell priming; ipilimumab; combined with PD-1 blockade.
Key PTMs / Glycobiology: N-glycosylated; affects surface retention
Co-inhibitory receptor on chronically activated T cells
IO Relevance / Indications: Co-inhibitory receptor; relatlimab approved with nivolumab in melanoma.
Key PTMs / Glycobiology: N-glycosylated; metalloprotease-shed soluble LAG-3
T/NK co-inhibitory receptor (galectin-9 axis)
IO Relevance / Indications: T-cell/NK co-inhibitory receptor (galectin-9 ligand); combined with PD-1 blockade.
Key PTMs / Glycobiology: N-glycosylated; shed soluble TIM-3
Co-inhibitory receptor competing with DNAM-1 in the PVR axis
IO Relevance / Indications: T/NK co-inhibitory receptor in PVR/CD155 axis; multiple anti-TIGIT + PD-(L)1 combos in trials.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Myeloid/T-cell co-inhibitory ligand
IO Relevance / Indications: Myeloid/T-cell checkpoint; investigational blockers combined with PD-1.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Co-inhibitory receptor (HVEM ligand)
IO Relevance / Indications: Co-inhibitory receptor (HVEM ligand); emerging immunomodulatory target.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Inhibitory NK/CD8 receptor engaging HLA-E
IO Relevance / Indications: Inhibitory NK/CD8 receptor; monalizumab blocks HLA-E-mediated suppression.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Adenosine receptor suppressing TCR signaling and IFN-γ
IO Relevance / Indications: Adenosine receptor limiting TCR signaling/IFN-g; antagonists (ciforadenant) with ICIs.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
TIGIT ligand sustaining T/NK suppression
IO Relevance / Indications: TIGIT/DNAM-1 ligand overexpressed in tumors; sustains immune escape.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Costimulatory agonist re-energizing effector/memory T cells (counters coercion)
IO Relevance / Indications: T-cell costimulatory receptor; agonist antibodies to boost effector/memory T cells.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Costimulatory agonist boosting T/NK cytotoxicity (counters coercion)
IO Relevance / Indications: Costimulatory receptor; agonists and bispecifics enhance T/NK cytotoxicity.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Agonism boosts effectors and destabilizes Tregs (counters coercion)
IO Relevance / Indications: Costimulatory TNFR; agonism depletes Tregs and boosts effector T cells.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
T-cell costimulator amplifying effector responses (counters coercion)
IO Relevance / Indications: T-cell costimulator; agonist/antagonist programs modulating effector vs Treg balance.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Tryptophan-catabolizing enzyme creating metabolic immunosuppression
IO Relevance / Indications: Tryptophan-catabolizing enzyme creating immunosuppressive TME; small-molecule inhibitors.
Key PTMs / Glycobiology: Regulated by phosphorylation / ubiquitination
Myeloid inhibitory receptor suppressing T cells
IO Relevance / Indications: Inhibitory receptor on AML/myeloid cells driving T-cell suppression; antibody programs.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Costimulatory receptor (CD70 axis) sustaining T-cell activation (counters coercion)
IO Relevance / Indications: T-cell costimulatory receptor (CD70 ligand); agonist antibodies in development.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Marks tumor-infiltrating Tregs that suppress effector cells
IO Relevance / Indications: Selectively marks tumor-infiltrating Tregs; depleting antibodies aim to relieve suppression.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Pan-tumor co-inhibitory ligand suppressing T-cell function
IO Relevance / Indications: Pan-tumor immunoregulatory protein; targeted by ADCs and radioconjugates (e.g. omburtamab).
Key PTMs / Glycobiology: N-glycosylated (B7-H3)
Antigen-directed modality; CD38 also fuels adenosine-driven coercion
IO Relevance / Indications: Myeloma antigen; daratumumab/isatuximab and radioimmunotherapy programs.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Immunosuppressive sialoglycan and tumor antigen (Siglec ligand).
IO Relevance / Indications: Immunosuppressive sialoglycan and tumor antigen (Siglec ligand).
Key PTMs / Glycobiology: Truncated sialylated O-glycan TACA
Immunomodulatory sialoglycan; Siglec ligand; neuroendocrine tumors.
IO Relevance / Indications: Immunomodulatory sialoglycan; Siglec ligand; neuroendocrine tumors.
Key PTMs / Glycobiology: Polysialylated glycan
Builds alpha2,6-sialoglycans engaging Siglec checkpoints (coercion).
IO Relevance / Indications: Builds alpha2,6-sialoglycans engaging Siglec checkpoints (coercion).
Key PTMs / Glycobiology: Sialyltransferase glyco-writer
Sialyl-T synthesis sustaining an immunosuppressive glycocalyx.
IO Relevance / Indications: Sialyl-T synthesis sustaining an immunosuppressive glycocalyx.
Key PTMs / Glycobiology: Sialyltransferase glyco-writer
IgG-Fc core fucosylation lowers ADCC; afucosylation enhances effector killing.
IO Relevance / Indications: IgG-Fc core fucosylation lowers ADCC; afucosylation enhances effector killing.
Key PTMs / Glycobiology: Core fucosyltransferase
Macrophage complement receptor suppressing T cells and promoting an immunosuppressive niche.
IO Relevance / Indications: Macrophage complement receptor suppressing T cells and promoting an immunosuppressive niche.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
PVR-axis co-inhibitory receptor competing with DNAM-1 on T/NK cells.
IO Relevance / Indications: PVR-axis co-inhibitory receptor competing with DNAM-1 on T/NK cells.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Co-inhibitory receptor for CD112; blockade pairs with TIGIT (e.g. COM701).
IO Relevance / Indications: Co-inhibitory receptor for CD112; blockade pairs with TIGIT (e.g. COM701).
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Ligand for PVRIG/TIGIT/DNAM-1 tuning effector suppression.
IO Relevance / Indications: Ligand for PVRIG/TIGIT/DNAM-1 tuning effector suppression.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Major non-MHC LAG-3 ligand mediating T-cell inhibition.
IO Relevance / Indications: Major non-MHC LAG-3 ligand mediating T-cell inhibition.
Key PTMs / Glycobiology: Secreted; N-glycosylated
Homophilic co-inhibitory receptor; partners with TIM-3 to suppress T/NK cells.
IO Relevance / Indications: Homophilic co-inhibitory receptor; partners with TIM-3 to suppress T/NK cells.
Key PTMs / Glycobiology: Heavily N-glycosylated
B7-family checkpoint signaling through KIR3DL3 to inhibit T cells.
IO Relevance / Indications: B7-family checkpoint signaling through KIR3DL3 to inhibit T cells.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Inhibitory receptor for HHLA2 on T/NK cells.
IO Relevance / Indications: Inhibitory receptor for HHLA2 on T/NK cells.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
HLA-engaging inhibitory receptor on myeloid/NK/T cells.
IO Relevance / Indications: HLA-engaging inhibitory receptor on myeloid/NK/T cells.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Myeloid inhibitory receptor sustaining suppressive macrophages (anti-ILT4 programs).
IO Relevance / Indications: Myeloid inhibitory receptor sustaining suppressive macrophages (anti-ILT4 programs).
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Collagen-binding inhibitory receptor dampening immune effectors.
IO Relevance / Indications: Collagen-binding inhibitory receptor dampening immune effectors.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Glyco-immune checkpoint on myeloid/T cells engaging tumor sialoglycans.
IO Relevance / Indications: Glyco-immune checkpoint on myeloid/T cells engaging tumor sialoglycans.
Key PTMs / Glycobiology: Sialoglycan-binding lectin; N-glycosylated
B7-family-like immunosuppressor on TAMs/tumor (anti-Siglec-15 e.g. NC318).
IO Relevance / Indications: B7-family-like immunosuppressor on TAMs/tumor (anti-Siglec-15 e.g. NC318).
Key PTMs / Glycobiology: Sialoglycan-binding lectin; N-glycosylated
Secreted lectin impairing T-cell function and reshaping the TME.
IO Relevance / Indications: Secreted lectin impairing T-cell function and reshaping the TME.
Key PTMs / Glycobiology: Beta-galactoside-binding lectin; MMP-cleaved; not itself glycosylated
Inhibitory killer Ig-like receptor restraining NK cytotoxicity (lirilumab class).
IO Relevance / Indications: Inhibitory killer Ig-like receptor restraining NK cytotoxicity (lirilumab class).
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Promotes Treg expansion/stability and suppressive myeloid cells.
IO Relevance / Indications: Promotes Treg expansion/stability and suppressive myeloid cells.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Treg trafficking receptor; depletion relieves suppression (mogamulizumab).
IO Relevance / Indications: Treg trafficking receptor; depletion relieves suppression (mogamulizumab).
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Stabilizes intratumoral Treg function and T-cell exhaustion.
IO Relevance / Indications: Stabilizes intratumoral Treg function and T-cell exhaustion.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Drives TAM recruitment/polarization; blockade reprograms suppressive myeloid (pexidartinib).
IO Relevance / Indications: Drives TAM recruitment/polarization; blockade reprograms suppressive myeloid (pexidartinib).
Key PTMs / Glycobiology: Receptor tyrosine kinase: ligand-induced autophosphorylation; N-glycosylated ECD
Recruits MDSCs/neutrophils via the IL-8/CXCL axis.
IO Relevance / Indications: Recruits MDSCs/neutrophils via the IL-8/CXCL axis.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Recruits monocytic MDSCs/TAMs into the TME.
IO Relevance / Indications: Recruits monocytic MDSCs/TAMs into the TME.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Depletes arginine to paralyze T cells (myeloid metabolic coercion).
IO Relevance / Indications: Depletes arginine to paralyze T cells (myeloid metabolic coercion).
Key PTMs / Glycobiology: Regulated by phosphorylation / ubiquitination
Tryptophan 2,3-dioxygenase; IDO-parallel kynurenine-driven suppression.
IO Relevance / Indications: Tryptophan 2,3-dioxygenase; IDO-parallel kynurenine-driven suppression.
Key PTMs / Glycobiology: Regulated by phosphorylation / ubiquitination
Kynurenine sensor enforcing tolerogenic T-cell/myeloid programs.
IO Relevance / Indications: Kynurenine sensor enforcing tolerogenic T-cell/myeloid programs.
Key PTMs / Glycobiology: Ligand-activated nucleocytoplasmic shuttling; phosphorylation
Metabolic enzyme generating AHR agonists that suppress immunity.
IO Relevance / Indications: Metabolic enzyme generating AHR agonists that suppress immunity.
Key PTMs / Glycobiology: Secreted; N-glycosylated
Degrades STING agonist cGAMP and yields adenosine; dual innate-suppression node.
IO Relevance / Indications: Degrades STING agonist cGAMP and yields adenosine; dual innate-suppression node.
Key PTMs / Glycobiology: Ecto-nucleotidase; N-glycosylated; shed soluble form
Second adenosine receptor reinforcing adenosinergic immunosuppression.
IO Relevance / Indications: Second adenosine receptor reinforcing adenosinergic immunosuppression.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
PGE2 receptor mediating myeloid/T-cell immunosuppression.
IO Relevance / Indications: PGE2 receptor mediating myeloid/T-cell immunosuppression.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Generates immunosuppressive PGE2 in the TME.
IO Relevance / Indications: Generates immunosuppressive PGE2 in the TME.
Key PTMs / Glycobiology: Regulated by phosphorylation / ubiquitination
Immunosuppressive cytokine restraining APC and T-cell activation.
IO Relevance / Indications: Immunosuppressive cytokine restraining APC and T-cell activation.
Key PTMs / Glycobiology: Secreted; N-glycosylated
Regulatory T-cell density; suppressive TME (coercion).
IO Relevance / Indications: Regulatory T-cell density; suppressive TME (coercion).
Key PTMs / Glycobiology: Phosphorylation/acetylation-regulated (nuclear)
Immunosuppressive M2 macrophages (coercion).
IO Relevance / Indications: Immunosuppressive M2 macrophages (coercion).
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Myeloid/MDSC infiltration (coercion).
IO Relevance / Indications: Myeloid/MDSC infiltration (coercion).
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Granulocytic MDSC marker.
IO Relevance / Indications: Granulocytic MDSC marker.
Key PTMs / Glycobiology: GPI-anchored, N-glycosylated
Terminal T-cell exhaustion from chronic coercion.
IO Relevance / Indications: Terminal T-cell exhaustion from chronic coercion.
Key PTMs / Glycobiology: Phosphorylation/acetylation-regulated (nuclear)
Serum tumor marker (CA19-9 ELISA); selectin/Siglec ligand.
IO Relevance / Indications: Serum tumor marker (CA19-9 ELISA); selectin/Siglec ligand.
Key PTMs / Glycobiology: Sialylated Lewis glycan
Stromal barrier driving immune exclusion (camouflage) and lowered CTL sensitivity (cytoprotection)
IO Relevance / Indications: Drives stromal immune exclusion and reduces CTL sensitivity; bintrafusp alfa and TGF-beta-pathway agents in trials.
Key PTMs / Glycobiology: Secreted latent complex (LAP); integrin/protease-activated; glycosylated
TGF-beta receptor enforcing immune exclusion and dampening CTL sensitivity (galunisertib, vactosertib).
IO Relevance / Indications: TGF-beta receptor enforcing immune exclusion and dampening CTL sensitivity (galunisertib, vactosertib).
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Intracellular granzyme-B inhibitor; shields tumor cells from CTL/NK killing.
IO Relevance / Indications: Intracellular granzyme-B inhibitor; shields tumor cells from CTL/NK killing.
Key PTMs / Glycobiology: Regulated by phosphorylation / ubiquitination
Anti-apoptotic; venetoclax re-sensitizes immune-resistant tumor cells.
IO Relevance / Indications: Anti-apoptotic; venetoclax re-sensitizes immune-resistant tumor cells.
Key PTMs / Glycobiology: Phosphorylation modulates anti-apoptotic activity; ubiquitin turnover
Anti-apoptotic guardian limiting effector-induced death.
IO Relevance / Indications: Anti-apoptotic guardian limiting effector-induced death.
Key PTMs / Glycobiology: Phosphodegron-driven ubiquitination/degradation
Anti-apoptotic protein resisting cytotoxic killing.
IO Relevance / Indications: Anti-apoptotic protein resisting cytotoxic killing.
Key PTMs / Glycobiology: Regulated by phosphorylation / ubiquitination
Blocks caspase-8/death-receptor apoptosis triggered by FasL/TRAIL.
IO Relevance / Indications: Blocks caspase-8/death-receptor apoptosis triggered by FasL/TRAIL.
Key PTMs / Glycobiology: Regulated by phosphorylation / ubiquitination
Caspase inhibitor; SMAC-mimetics restore death-receptor sensitivity.
IO Relevance / Indications: Caspase inhibitor; SMAC-mimetics restore death-receptor sensitivity.
Key PTMs / Glycobiology: Regulated by phosphorylation / ubiquitination
Apoptosis inhibitor targeted by SMAC mimetics to lower the death threshold.
IO Relevance / Indications: Apoptosis inhibitor targeted by SMAC mimetics to lower the death threshold.
Key PTMs / Glycobiology: Regulated by phosphorylation / ubiquitination
Negative regulator of IFN/TNF signaling; loss sensitizes to immunotherapy.
IO Relevance / Indications: Negative regulator of IFN/TNF signaling; loss sensitizes to immunotherapy.
Key PTMs / Glycobiology: Regulated by phosphorylation / ubiquitination
Phosphatase paired with PTPN2; dual inhibition boosts cytokine responsiveness.
IO Relevance / Indications: Phosphatase paired with PTPN2; dual inhibition boosts cytokine responsiveness.
Key PTMs / Glycobiology: Regulated by phosphorylation / ubiquitination
Suppresses dsRNA/ISG-driven death; inhibition overcomes checkpoint resistance.
IO Relevance / Indications: Suppresses dsRNA/ISG-driven death; inhibition overcomes checkpoint resistance.
Key PTMs / Glycobiology: Regulated by phosphorylation / ubiquitination
Restrains TNF-induced cell death, raising the cytotoxicity threshold.
IO Relevance / Indications: Restrains TNF-induced cell death, raising the cytotoxicity threshold.
Key PTMs / Glycobiology: Regulated by phosphorylation / ubiquitination
Dampens IFN-gamma/JAK-STAT signaling, blunting cytokine-mediated killing.
IO Relevance / Indications: Dampens IFN-gamma/JAK-STAT signaling, blunting cytokine-mediated killing.
Key PTMs / Glycobiology: Regulated by phosphorylation / ubiquitination
Cytotoxic effector activity; reads out the killing tumors must resist (cytoprotection axis).
IO Relevance / Indications: Cytotoxic effector activity; reads out the killing tumors must resist (cytoprotection axis).
Key PTMs / Glycobiology: Granule serine protease; released on degranulation; N-glycosylated
In vivo early-response imaging of effector-cell killing.
IO Relevance / Indications: In vivo early-response imaging of effector-cell killing.
Key PTMs / Glycobiology: N/A (in vivo imaging agent)
Effector cytolytic capacity.
IO Relevance / Indications: Effector cytolytic capacity.
Key PTMs / Glycobiology: Granule pore-former; glycosylation-dependent; surface-PS can block it
18-gene inflamed signature predicting anti-PD-1 benefit; defines 'hot' tumors.
IO Relevance / Indications: 18-gene inflamed signature predicting anti-PD-1 benefit; defines 'hot' tumors.
Key PTMs / Glycobiology: N/A (composite biomarker)
Neoantigen-load proxy; TMB-high (>=10 mut/Mb) is a tumor-agnostic ICI indication.
IO Relevance / Indications: Neoantigen-load proxy; TMB-high (>=10 mut/Mb) is a tumor-agnostic ICI indication.
Key PTMs / Glycobiology: N/A (composite biomarker)
Validated spatial T-cell density score; prognostic and phenotype-defining.
IO Relevance / Indications: Validated spatial T-cell density score; prognostic and phenotype-defining.
Key PTMs / Glycobiology: N/A (composite biomarker)
Cytotoxic T-cell infiltration; core to hot / excluded / desert classification.
IO Relevance / Indications: Cytotoxic T-cell infiltration; core to hot / excluded / desert classification.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
In vivo CD8 mapping (crefmirlimab) for response/PD – bridges phenotyping and theranostics.
IO Relevance / Indications: In vivo CD8 mapping (crefmirlimab) for response/PD – bridges phenotyping and theranostics.
Key PTMs / Glycobiology: N/A (in vivo imaging agent)
Total T-cell content; Immunoscore component.
IO Relevance / Indications: Total T-cell content; Immunoscore component.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Helper T-cell compartment.
IO Relevance / Indications: Helper T-cell compartment.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Total tumor-associated macrophage content.
IO Relevance / Indications: Total tumor-associated macrophage content.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
NK-cell content.
IO Relevance / Indications: NK-cell content.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Proliferating (reinvigorated) T cells / tumor proliferation.
IO Relevance / Indications: Proliferating (reinvigorated) T cells / tumor proliferation.
Key PTMs / Glycobiology: Phosphorylation/acetylation-regulated (nuclear)
Effector cytokine anchoring the inflamed signature.
IO Relevance / Indications: Effector cytokine anchoring the inflamed signature.
Key PTMs / Glycobiology: Secreted; N-glycosylated
Progenitor-exhausted T cells predicting durable ICI response.
IO Relevance / Indications: Progenitor-exhausted T cells predicting durable ICI response.
Key PTMs / Glycobiology: Phosphorylation/acetylation-regulated (nuclear)
Th1/effector polarization.
IO Relevance / Indications: Th1/effector polarization.
Key PTMs / Glycobiology: Phosphorylation/acetylation-regulated (nuclear)
Memory T-cell compartment.
IO Relevance / Indications: Memory T-cell compartment.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Early activation / tissue-resident memory.
IO Relevance / Indications: Early activation / tissue-resident memory.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Tertiary lymphoid structure formation; favorable ICI phenotype.
IO Relevance / Indications: Tertiary lymphoid structure formation; favorable ICI phenotype.
Key PTMs / Glycobiology: Secreted; N-glycosylated
Tumor-associated antigen exploited for cytotoxic payload delivery
IO Relevance / Indications: Validated ADC antigen; trastuzumab deruxtecan/emtansine across breast, gastric, lung.
Key PTMs / Glycobiology: Receptor tyrosine kinase: ligand-induced autophosphorylation; N-glycosylated ECD
Epithelial antigen exploited for payload delivery
IO Relevance / Indications: Broadly expressed epithelial antigen; sacituzumab govitecan, datopotamab deruxtecan.
Key PTMs / Glycobiology: N-glycosylated; glycosylation influences TROP2 ADC binding
Urothelial antigen exploited for payload delivery
IO Relevance / Indications: Urothelial cancer antigen; enfortumab vedotin.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Lymphoma antigen exploited for payload delivery
IO Relevance / Indications: Hodgkin/ALCL antigen; brentuximab vedotin.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
B-cell antigen exploited for payload delivery
IO Relevance / Indications: B-cell antigen; inotuzumab ozogamicin in B-ALL.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
B-cell antigen exploited for payload delivery
IO Relevance / Indications: B-cell receptor component; polatuzumab vedotin in DLBCL.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
B-cell antigen for ADC/CAR-T/bispecific targeting
IO Relevance / Indications: Pan-B-cell antigen; loncastuximab tesirine ADC, CAR-T and bispecific platforms.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Plasma-cell antigen for ADC/CAR-T/bispecific targeting
IO Relevance / Indications: Plasma-cell antigen in myeloma; belantamab mafodotin ADC, CAR-T, bispecifics.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Myeloid antigen exploited for payload delivery
IO Relevance / Indications: Myeloid antigen; gemtuzumab ozogamicin in AML.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Resistance-associated RTK exploited for payload delivery
IO Relevance / Indications: Resistance-associated RTK; patritumab deruxtecan in EGFR-mutant NSCLC.
Key PTMs / Glycobiology: Receptor tyrosine kinase: ligand-induced autophosphorylation; N-glycosylated ECD
RTK antigen exploited for payload delivery
IO Relevance / Indications: RTK overexpressed in NSCLC/GI; telisotuzumab vedotin.
Key PTMs / Glycobiology: Receptor tyrosine kinase: ligand-induced autophosphorylation; N-glycosylated ECD
Oncogenic RTK exploited for payload delivery
IO Relevance / Indications: Validated oncogenic RTK; multiple EGFR-directed ADCs.
Key PTMs / Glycobiology: Receptor tyrosine kinase: ligand-induced autophosphorylation; N-glycosylated ECD
Mesenchymal RTK exploited for payload delivery
IO Relevance / Indications: Mesenchymal/resistance RTK; ADCs in solid tumors.
Key PTMs / Glycobiology: Receptor tyrosine kinase: ligand-induced autophosphorylation; N-glycosylated ECD
Onco-fetal RTK for ADC/CAR-T targeting
IO Relevance / Indications: Onco-fetal RTK in hematologic and solid tumors; zilovertamab vedotin.
Key PTMs / Glycobiology: Receptor tyrosine kinase: ligand-induced autophosphorylation; N-glycosylated ECD
Tight-junction antigen for mAb/ADC/CAR-T targeting
IO Relevance / Indications: Gastric/pancreatic tight-junction antigen; zolbetuximab, ADCs, CAR-T.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
HCC antigen for ADC/CAR-T targeting
IO Relevance / Indications: Hepatocellular carcinoma antigen; ADC and CAR-T programs.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Ovarian mucin exploited for payload delivery
IO Relevance / Indications: Ovarian cancer mucin; ADC and bispecific programs.
Key PTMs / Glycobiology: Massive O-glycosylation (mucin); aberrant tumor glycoforms (CA-125)
Mesothelioma/ovarian antigen for ADC/CAR-T targeting
IO Relevance / Indications: Mesothelioma/ovarian/pancreatic antigen; anetumab and CAR-T.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Prostate antigen for ADC/T-cell-engager targeting
IO Relevance / Indications: Prostate cancer antigen; ADCs and T-cell engagers.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Onco-fetal antigen exploited for payload delivery
IO Relevance / Indications: Onco-fetal antigen broadly expressed in carcinomas; ADC programs.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Breast antigen exploited for payload delivery
IO Relevance / Indications: Breast cancer antigen; ladiratuzumab vedotin.
Key PTMs / Glycobiology: N-glycosylated zinc transporter (LIV-1)
Tumor-expressed coagulation factor for payload delivery
IO Relevance / Indications: Coagulation factor overexpressed in solid tumors; tisotumab vedotin in cervical cancer.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Ovarian/lung antigen exploited for payload delivery
IO Relevance / Indications: Phosphate transporter in ovarian/lung cancer; ADC programs.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
AML/BPDCN antigen exploited for payload/fusion-toxin delivery
IO Relevance / Indications: AML/BPDCN antigen; tagraxofusp and CD123 ADCs/bispecifics.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Ovarian antigen for ADC and folate-based imaging/therapy
IO Relevance / Indications: Ovarian cancer antigen; mirvetuximab soravtansine; folate-based imaging/therapy.
Key PTMs / Glycobiology: GPI-anchored, N-glycosylated
Epithelial antigen for ADC and anti-CEA imaging
IO Relevance / Indications: GI/lung epithelial antigen; tusamitamab ravtansine and anti-CEA imaging agents.
Key PTMs / Glycobiology: GPI-anchored, heavily N-glycosylated; carries Lewis / sialyl-Lewis glycans
SCLC antigen for ADC/bispecific/radioligand delivery
IO Relevance / Indications: Small-cell lung cancer antigen; tarlatamab bispecific, ADCs, radioconjugates.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Prostate receptor for PSMA PET imaging and Lu-177 radioligand therapy
IO Relevance / Indications: Prostate cancer; Ga-68/F-18 PSMA PET imaging and Lu-177-PSMA-617 (Pluvicto) therapy.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
NET receptor for DOTATATE imaging and radioligand therapy
IO Relevance / Indications: Neuroendocrine tumors; Ga-68-DOTATATE imaging and Lu-177-DOTATATE (Lutathera) therapy.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Tumor-homing chemokine receptor for pentixafor/pentixather (also shapes immune trafficking)
IO Relevance / Indications: Hematologic/solid tumors; pentixafor imaging and pentixather therapy.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Bombesin receptor for radioligand imaging/therapy
IO Relevance / Indications: Prostate/breast cancer; bombesin-analog radioligands (Ga-68/Lu-177).
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Gastrin receptor for radioligand imaging/therapy
IO Relevance / Indications: Medullary thyroid carcinoma; minigastrin-based radioligands.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Neurotensin receptor for radioligand imaging/therapy
IO Relevance / Indications: Pancreatic/other adenocarcinomas; neurotensin-analog radioligands.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Hypoxia/RCC marker for radioligand delivery (hypoxia indirectly enables evasion)
IO Relevance / Indications: Clear-cell RCC/hypoxia marker; girentuximab imaging and radioconjugates.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
B-cell antigen for radioimmunotherapy
IO Relevance / Indications: B-cell lymphoma; radioimmunotherapy (Y-90 ibritumomab tiuxetan).
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Angiogenesis integrin subunit for RGD radioligand delivery
IO Relevance / Indications: Tumor angiogenesis marker; RGD-peptide PET/radioligand imaging and therapy.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Angiogenesis integrin subunit for RGD radioligand delivery
IO Relevance / Indications: Beta-3 subunit of the angiogenesis integrin targeted by RGD radioligands.
Key PTMs / Glycobiology: N-glycosylated extracellular domain
Neuroblastoma glycolipid antigen exploited for mAb/radioligand delivery
IO Relevance / Indications: Neuroblastoma disialoganglioside; dinutuximab and GD2 radioconjugates. Glycolipid antigen – no protein UniProt ID.
Key PTMs / Glycobiology: Disialoganglioside GD2 – the glycan IS the antigen; O-acetylated variants exist
Melanoma/neuroblastoma ganglioside; mAb/ADC and vaccine programs.
IO Relevance / Indications: Melanoma/neuroblastoma ganglioside; mAb/ADC and vaccine programs.
Key PTMs / Glycobiology: Disialoganglioside TACA (the glycan is the antigen)
Melanoma ganglioside; vaccine and antibody programs.
IO Relevance / Indications: Melanoma ganglioside; vaccine and antibody programs.
Key PTMs / Glycobiology: Ganglioside TACA
SCLC-restricted ganglioside; anti-FucGM1 (BMS-986012).
IO Relevance / Indications: SCLC-restricted ganglioside; anti-FucGM1 (BMS-986012).
Key PTMs / Glycobiology: Fucosylated monosialoganglioside TACA
Breast/epithelial vaccine and ADC target.
IO Relevance / Indications: Breast/epithelial vaccine and ADC target.
Key PTMs / Glycobiology: Globo-series glycosphingolipid TACA
Glycolytic enzyme converting pyruvate to lactate; tumor lactate accumulation suppresses NFAT signaling and IFN-γ production in T/NK cells.
IO Relevance / Indications: Drives glycolytic lactate production creating an acidic, immunosuppressive TME; small-molecule LDHA inhibitors (e.g. ML-05) under investigation to restore T-cell function and sensitize to checkpoint blockade.
Key PTMs / Glycobiology: Regulated by phosphorylation; acetylation modulates activity; ubiquitination-linked turnover
Lactate exporter; high tumor expression depletes T-cell access to glucose and sustains an immunosuppressive acidic niche.
IO Relevance / Indications: Lactate efflux transporter negatively correlated with anti-PD-1 efficacy; high expression linked to Treg, Th2, and immunosuppressive checkpoint enrichment (PD-1, PD-L1, TIM-3) in lung cancer and glioma.
Key PTMs / Glycobiology: Multi-pass transmembrane glycoprotein; N-glycosylated
Paired lactate/pyruvate transporter; contributes to TME acidification and immunosuppressive cell infiltration alongside MCT4.
IO Relevance / Indications: Bidirectional lactate/pyruvate transporter; interacts with immune checkpoints (PD-1, PD-L1, PD-L2, TIM-3) and immunosuppressive factors (TGF-β, IL-10) in glioma; selectively inhibited by AZD3965 in clinical development.
Key PTMs / Glycobiology: Multi-pass transmembrane glycoprotein; N-glycosylated
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