Vector Laboratories in Immuno-Oncology, Part 2: Necroptosis, Metabolic Checkpoints, & Tumor-Nerve Signaling

Immuno-oncology research spans a wide range of biology, from RNA sensing and metabolism to the nervous system and glycosylation, and each new study adds to our understanding of how the immune system interacts with cancer. A selection of five  publications, spanning innate immune sensing, obesity-linked immunosuppression, intracranial CAR T cell delivery, tumor-nerve signaling, and cancer stemness glycobiology, show how Vector Laboratories antibodies, lectins, and detection reagents, continue to support immuno-oncology research from mechanistic discovery through early-phase clinical trials.

ADAR1 Masks the Cancer Immunotherapeutic Promise of ZBP1-Driven Necroptosis

Nature (2022) — PMID: PMC9373927

Zhang, Yin, Fedorov, and colleagues describe how the RNA-editing enzyme ADAR1 blocks a cell-death pathway relevant to cancer immunotherapy. ADAR1 is a determinant of resistance to immune checkpoint blockade (ICB)-based therapy and normally limits the buildup of immunogenic Z-form double-stranded RNA (Z-RNA). When Z-RNA buildup is allowed to occur, the sensor ZBP1 detects it and triggers RIPK3-mediated necroptosis. The team identified a small molecule, CBL0137, that activates ZBP1-driven necroptosis by inducing Z-DNA formation independent of ADAR1 status and showed that it reversed resistance to ICB in mouse melanoma models.

To confirm Z-nucleic acid accumulation across these experiments, the researchers used an anti-Z-DNA/Z-RNA antibody, clone Z22 from Absolute Antibody, a Vector Laboratories brand, for immunofluorescence imaging. These findings point to ZBP1-driven necroptosis as a route to rekindle immune responsiveness in human cancers resistant to immune checkpoint therapies.

Obesity Induces PD-1 on Macrophages to Suppress Anti-Tumor Immunity

Nature (2024) — PMCID: PMC11456854

Bader, Wolf, Rathmell, and colleagues investigated the connection between cancer and obesity, a common cancer risk factor yet to be associated with enhanced response to ICB therapies. They found that obesity selectively induces PD-1 expression on tumor-associated macrophages (TAMs). Type I cytokines, adipokines such as leptin, and free fatty acids like palmitate drove this PD-1 expression through mTORC1- and glycolysis-linked signaling. PD-1 then suppressed macrophage glycolysis, phagocytosis, and antigen presentation, blunting anti-tumor activity. Across several mouse tumor models, a high-fat diet both accelerated tumor growth and improved response to anti-PD-1 therapy, and elevated macrophage PD-1 was confirmed in human kidney and endometrial tumor samples, including biopsies taken before and after patient weight loss.

To visualize PD-1 and macrophage markers in tumor tissue by multiplexed immunohistochemistry, the team used Normal Horse Serum Blocking Solution, 2.5% and HRP-conjugated anti-rabbit and anti-mouse secondary antibodies. For in vivo tumor modeling, they used the MC38 colorectal cancer cell line, sourced from Kerafast, a Vector Laboratories brand. For immuno-oncology, the data suggest that a patient’s metabolic status, not tumor genetics alone, can shape macrophage checkpoint expression and response to PD-1 blockade.

Intrathecal Bivalent CAR T Cells Targeting EGFR and IL13Rα2 in Recurrent Glioblastoma: Phase 1 Trial Interim Results

Nature Medicine (2024) — PMCID: PMC13123313

Bagley, Logun, Binder, O’Rourke, and colleagues report interim results from a phase I trial of intrathecally delivered bivalent CAR T cells targeting both EGFR and IL13Rα2 in six patients with recurrent, multifocal glioblastoma, a disease with a median overall survival rate under one year. Early imaging showed reductions in tumor enhancement and size in all six patients, though none met formal response criteria, and one patient experienced dose-limiting toxicity consistent with immune effector cell-associated neurotoxicity syndrome, managed with dexamethasone and anakinra. CAR T cells and elevated cytokines were detectable in cerebrospinal fluid across all patients, indicating that the cells were active in the central nervous system. A related, larger trial using intracerebroventricular delivery of the same bivalent construct in 18 patients later reported tumor regression in 8 of 13 evaluable patients, with one confirmed partial response.

To confirm tumor expression of both CAR T cell targets, researchers stained tissue sections with anti-EGFRvIII antibody, clone 806 from Absolute Antibody, alongside an anti-IL13Rα2 antibody. The trial offers early, patient-level evidence that a single CAR T product can be engineered and delivered locally to act on two independent glioblastoma antigens at once.

Further reading: Related phase 1 trial using intracerebroventricular delivery (Nature Medicine, 2025)

Nociceptor Neurons Affect Cancer Immunosurveillance

Nature (2022) — DOI: 10.1038/s41586-022-05374-w

Balood, Ahmadi, Eichwald, and colleagues, led by Sebastien Talbot, describe a neuroimmune circuit that helps tumors evade immune attack. Melanoma cells secrete secretory leukocyte protease inhibitor (SLPI), which activates pain-sensing dorsal root ganglion (DRG) neurons and increases their release of the neuropeptide CGRP. CGRP then binds the RAMP1 receptor on CD8+ T cells, driving a PD-1+LAG3+TIM3+ exhaustion phenotype. Genetically ablating nociceptors, silencing them pharmacologically, or blocking RAMP1 each slowed tumor growth and reduced T cell exhaustion in mouse models, and RAMP1-high CD8+ T cells in human melanoma samples correlated with worse survival.

To test whether SLPI directly activates sensory neurons, the team loaded cultured DRG neurons with a calcium indicator and stimulated them with recombinant mouse SLPI protein from LSBio, a Vector Laboratories company, then rinsed and mounted the cells in VECTASHIELD Antifade Mounting Medium with DAPI. The findings identify the sensory nervous system, not just tumor or immune cells, as a potential target for restoring T cell function in checkpoint-resistant tumors.

Identification of Stemness-Related Glycosylation Changes in Head and Neck Squamous Cell Carcinoma

BMC Cancer (2024) — DOI: 10.1186/s12885-024-12161-5

Routila, Leivo, and colleagues profiled the glycosylation of four stemness-associated proteins, OCT4, CIP2A, MET, and LIMA1, across tumor tissue, serum, and cell lysates from 25 head and neck squamous cell carcinoma (HNSCC) patients. The data show a strong correlation between the glycosylation profiles of all four proteins within tumor tissue, pointing to a shared mannose- and galactose-rich glycosylation niche associated with cancer stemness, largely independent of where each protein sits inside the cell.

To profile glycan structures on tumor tissue, the researchers conjugated a panel of lectins, including Concanavalin A (ConA), Ulex Europaeus Agglutinin I (UEA-I), Soybean Agglutinin (SBA), Aleuria Aurantia Lectin (AAL), Maackia Amurensis Lectin (MAA/MAL I), and Wisteria Floribunda Lectin (WFL), all purchased from Vector Laboratories, onto nanoparticles for a bioaffinity glycoprofiling assay. For immuno-oncology, glycosylation changes tied to stemness contribute to immune evasion and therapy resistance, making this kind of glycan mapping relevant to identifying new immunotherapy targets in HNSCC.

Vector Laboratories: Bridging Discovery and Therapeutic Development

This group of studies spans RNA sensing, metabolism, the nervous system, and glycobiology, each contributing a different piece of the immuno-oncology picture, from mechanisms of immune resistance to the clinical delivery of CAR T-cell therapy. Vector Laboratories’ antibodies, detection reagents, and scientific expertise continue to give researchers the tools they need to ask these kinds of questions, and to answer them with confidence.

Full citations and links to each study are above, and more information on Vector Laboratories’ immuno-oncology portfolio is available here.