21 May 2025
Blood Proteomics: Insights into Cancer Immunotherapy
Research shows the tumor microenvironment’s key role in therapy resistance. RayBiotech’s platforms profile 8000+ proteins, aiding in mapping tumor-immune interactions, identifying biomarkers, and uncovering drug resistance.
Tumor Microenvironment in Cancer Immunotherapy
Decades of intensive research into the tumor microenvironment (TME) have revealed its crucial role in modulating therapeutic efficacy and resistance through dynamic cellular crosstalk. Tumor stromal cells secrete diverse signaling molecules that drive oncogenic pathways, immune evasion, and epigenetic reprogramming. These complex signaling networks present both challenges and opportunities for therapeutic intervention.
Proteomic Technology in Cancer Immunotherapy
Recent advances in affinity proteomic technology have enabled systematic interrogation of TME-derived factors through high-throughput protein profiling. RayBiotech’s Antibody Array platforms have pushed the limits of multi-analyte profiling, expanding array panels which previously captured several hundred proteins to 8000+ proteins, while maintaining their ng to pg/ml sensitivity. These high-density array platforms have emerged as powerful tools for mapping tumor-immune interactions, identifying predictive biomarkers and uncovering drug resistance mechanisms.
Overcoming Resistance with Blood Proteomics
Immune checkpoint inhibitors (ICIs) have transformed cancer treatment for patients with locally advanced or metastatic solid tumors, offering significant survival benefits across several cancer types. Nevertheless, the efficacy of ICI therapy is sometimes limited by primary or adaptive resistance. There is thus an urgent need for predictive biomarkers to better identify responders and optimize patient selection.
Noninvasive Monitoring with Blood Proteomics
RayBiotech’s antibody arrays have proven useful in many studies where cytokine profiling of blood revealed critical insights into the tumor microenvironment after ICI, highlighting the utility of this approach in noninvasive monitoring and therapy personalization. We outline 2 case studies demonstrating how RayBiotech’s array technology identified predictive biomarkers and mechanisms of resistance or response.
Case Study 1: Neutrophil-driven resistance in NSCLC
Harel et al. used the Quantibody® Kiloplex Array to profile 1000 plasma proteins in NSCLC patients receiving ICIs. Non-responders exhibited elevated CXCL8 and CXCL10, chemokines linked to neutrophil recruitment and immunosuppressive pathways (MAPK, NF-kappa B). These patients also showed upregulated neutrophil-related proteins (GRO, PLAUR, PILRA) and metabolic pathways favoring immune evasion. Antibody arrays revealed that combination therapy (ICIs + chemotherapy) improved response rates, suggesting targeting these pathways could overcome resistance.
Case Study 2: Cytokine signatures predict complete response
Laza-Briviesca et al. identified baseline cytokine profiles predictive of complete pathological response in NSCLC patients undergoing neoadjuvant chemoimmunotherapy. The RayBio® Cytokine Array G4000 showed that responders had lower levels of immunosuppressive factors (NT-3, beta-NGF, VEGF-D) pre-treatment. Post-treatment, they showed increased immune-activating markers (4-1BB, MCSF) and reduced immunosuppressive cytokines (Flt-3L, MPIF-1).
Conclusion: Advancing Cancer Immunotherapy
These studies demonstrate antibody arrays’ capacity to advance precision oncology through biomarker-based personalization. By enabling simultaneous detection of multiple cytokines in peripheral blood, arrays can open the door to non-invasive, accessible, and real-time monitoring of patient systemic immune responses, and ultimately inform targeted interventions like cytokine inhibition or combination regimens.
References
- Harel, M., et al. “Longitudinal Plasma Proteomic Profiling of Patients with Non-Small Cell Lung Cancer Undergoing Immune Checkpoint Blockade.” Journal for ImmunoTherapy of Cancer, vol. 10, 2022, e004582. https://doi.org/10.1136/jitc-2022-004582.
- Laza-Briviesca, R., et al. “Blood Biomarkers Associated to Complete Pathological Response on NSCLC Patients Treated with Neoadjuvant Chemoimmunotherapy.” Clinical and Translational Medicine, vol. 11, 2021, e491. https://doi.org/10.1002/ctm2.491.
- Gonzalez, C., et al. “TLR5 Agonists Enhance Anti-Tumor Immunity and Overcome Resistance to Immune Checkpoint Therapy.” Communications Biology, vol. 6, 2023, 31. https://doi.org/10.1038/s42003-022-04403-8.