Abstract
The culmination of over a century’s work to understand the role of the immune system in tumor control has led to the recent advances in cancer immunotherapies that have resulted in durable clinical responses in patients with a variety of malignancies. Cancer immunotherapies are rapidly changing traditional treatment paradigms and expanding the therapeutic landscape for cancer patients. However, despite the current success of these therapies, not all patients respond to immunotherapy and even those that do often experience toxicities. Thus, there is a growing need to identify predictive and prognostic biomarkers that enhance our understanding of the mechanisms underlying the complex interactions between the immune system and cancer. Therefore, the Society for Immunotherapy of Cancer (SITC) reconvened an Immune Biomarkers Task Force to review state of the art technologies, identify current hurdlers, and make recommendations for the field. As a product of this task force, Working Group 2 (WG2), consisting of international experts from academia and industry, assembled to identify and discuss promising technologies for biomarker discovery and validation. Thus, this WG2 consensus paper will focus on the current status of emerging biomarkers for immune checkpoint blockade therapy and discuss novel technologies as well as high dimensional data analysis platforms that will be pivotal for future biomarker research. In addition, this paper will include a brief overview of the current challenges with recommendations for future biomarker discovery.
Highlights
The role of the immune system in cancer control has been debated for over a century
A high frequency of Melan-A or NY-ESO-1 specific CD8+ T cells were detected in melanoma and prostate cancer patients who showed a clinical response to anti-cytotoxic T lymphocyteassociated antigen 4 (CTLA-4) therapy [55, 59]
programmed cell death ligand 1 (PD-L1) expression on tumor-infiltrating immune cells was significantly associated with clinical response in non-small cell lung cancer (NSCLC) patients treated with atezolizumab [28]
Summary
The role of the immune system in cancer control has been debated for over a century. The field of cancer immunology has progressed with knowledge obtained from animal studies, accumulated clinical observations and translational research. Improved high-throughput technologies are providing feasible tools for analyzing the mutation antigen profile, the gene signature and epigenetic modification of tumor and immune cells, the breadth of antibody responses, as well as the magnitude, homing capacity, cytotoxic function and T cell receptor (TCR) repertoire of T lymphocytes. It was shown that patients who clinically responded to CTLA-4 blockade developed an enhanced antibody response to a greater number of endogenous antigens than non-responders.
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