Abstract
Immunotherapies have emerged as one of the most promising approaches to treat patients with cancer. Recently, there have been many clinical successes using checkpoint receptor blockade, including T cell inhibitory...
Highlights
Increased understanding of cellular and molecular tumor immunology over the past two decades has enabled the identification of new ways to manipulate the immune response against cancer to counteract immunosuppressive mechanisms that evolve during tumor progression
A wide range of biomarkers and assays is required to guide cancer therapy for several reasons: i) a variety of immunotherapy agents with different mechanisms of action including immunotherapies that target activating and inhibitory T cell receptors (e.g., cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death-1 (PD-1)), adoptive T cell therapies that include tissue infiltrating lymphocytes (TILs), chimeric antigen receptors (CARs), and T cell receptor (TCR) modified T cells [18]; ii) tumor heterogeneity including changes in antigenic profiles over time and location for an individual patient; and iii) a variety of immune-suppressive mechanisms that are active in the tumor microenvironment (TME)
Recent data showed that measuring immune-related biomarkers, including T cell specific, antigen presentation–related, and IFNγ signaling–related genes, may allow for improved selection of patients likely to respond to anti–PD-1 therapy with pembrolizumab consistent with the hypothesis that clinical responses to PD-1 blockade occur in patients with a preexisting interferon-mediated adaptive immune response [61, 62]
Summary
Increased understanding of cellular and molecular tumor immunology over the past two decades has enabled the identification of new ways to manipulate the immune response against cancer to counteract immunosuppressive mechanisms that evolve during tumor progression. Enzyme-linked ImmunoSpot (ELISpot) Enzyme-Linked ImmunoSpot (ELISpot) is a highly quantitative assay for monitoring the secretion of cytokines and cytotoxic mediators (e.g., perforin, granzyme B) It can measure a wide range of cellular responses and is capable of assessing critical immune-related activity of antigen-specific T cell stimulation. The IFNγ ELISpot assay has been used extensively for monitoring immune responses in the development of vaccines for the prevention and treatment of infectious diseases; there is a body of literature demonstrating the correlation of the clinical outcome of cancer patients in immunotherapeutic trials with ELISpot results [21, 22]. Considering that the tumor infiltration is a reflection of a pre-existing immunity and is predictive of response to anti-checkpoint immunotherapy (discussed below), it appears logical to assume that functional assessment of cytotoxic activity of CD8+ T cells following stimulation with specific tumor associated antigen(s) by ELISpot may be predictive of response to immunotherapy. Clinical validation of the technology has been established in non-M3 AML, with classifiers for the prediction of response to frontline standard induction therapy in the elderly and pediatric populations [28, 29]
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