Biomarkers for Response to Immune Checkpoint Blockade

Abstract

Immune checkpoint blockade (ICB) has significant clinical activity in diverse cancer classes and can induce durable remissions in even refractory advanced disease. However, only a minority of cancer patients treated with ICB have long-term benefits, and ICB treatment is associated with significant, potentially life-threatening, autoimmune side effects. There is a great need to develop biomarkers of response to guide patient selection to maximize the chance of benefit and prevent unnecessary toxicity, and current biomarkers do not have optimal positive or negative predictive value. A variety of potential biomarkers are currently being developed, including those based on assessment of checkpoint protein expression, evaluation of tumor-intrinsic features including mutation burden and viral infection, evaluation of features of the tumor immune microenvironment including nature of immune cell infiltration, and features of the host such as composition of the gut microbiome. Better understanding of the underlying fundamental mechanisms of immune response and resistance to ICB, along with the use of complementary assays that interrogate distinct features of the tumor, the tumor microenvironment, and host immune system, will allow more precise use of these therapies to optimize patient outcomes.

The MHC Class-I Transactivator NLRC5: Implications to Cancer Immunology and Potential Applications to Cancer Immunotherapy

“…Biomarkers that can reliably predict responsiveness to ICI therapy are not yet available [ 282 ]. As it is unlikely that a single biomarker would have the predictive power, efforts are being made to develop a scoring system using multiple parameters [ 283 , 284 , 285 ]. In parallel, combinatorial approaches using a second checkpoint inhibitor, radiation, chemotherapy, ACT using CAR-T cells and oncolytic virus therapy are being investigated to improve the outcome of ICI therapy [ 286 , 287 , 288 , 289 ].…”

Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant

“…Currently, in order to test the clinical response to ICI therapy, there is a need to identify patients who would be expected to benefit from this immunotherapy ( 66 , 67 ). 5-methylcytosine and 5-hydroxymethylcytosine may act as prognostic and predictive biomarkers of ICI-sensitive cancers ( 68 ).…”

“…5-methylcytosine and 5-hydroxymethylcytosine may act as prognostic and predictive biomarkers of ICI-sensitive cancers ( 68 ). Thus, exploration of multimodal predictive models of target assessment, tumor-intrinsic features, independent host features, and the tumor microenvironment are needed to optimize the treatment of ICIs in the future ( 66 ).…”

The Role of Human Papilloma Virus in Dictating Outcomes in Head and Neck Squamous Cell Carcinoma

“…Non-cancer cells possess immune-checkpoint proteins, which act as a protective mechanism, preventing an autoimmune attack on the host. In cancer evolution, neoplastic cells possess such checkpoint proteins, and thus evade the host immune system ( Ganesan and Mehnert, 2020 ). Targeting the immune checkpoints prevents evasion of the immune response to the cancer.…”