4.6 Article

Predictive biomarkers for response to immune checkpoint inhibition

Journal

SEMINARS IN CANCER BIOLOGY
Volume 79, Issue -, Pages 4-17

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcancer.2021.03.036

Keywords

Immunotherapy; Predictive biomarkers; PD-L1; Tumour mutation burden (TMB); Microsatellite instability high (MSI-H)

Categories

Funding

  1. NIHR RM/ICR Biomedical Research Centre for cancer
  2. Cancer Research UK [C50947/A18176]
  3. National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal VMarsden Hospital
  4. Institute of Cancer Research [A109]
  5. The Rosetrees Trust [A2204]
  6. Ventana Medical Systems Inc [10467, 10530]

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Immune checkpoint inhibitors have transformed cancer treatment but many patients still do not benefit. Investigating biomarkers of resistance and response, particularly in host and tumor genomics, can lead to the discovery of new therapeutic targets and personalized treatment strategies. Multivariate multiomic markers may provide a more accurate assessment of response prediction.
Immune checkpoint inhibitors have transformed the prognosis and treatment paradigm of many cancer types, through the potential for durable responses. However, the majority of patients still do not benefit. Response to checkpoint inhibition is determined by dynamic host, tumour and tumour microenvironment factors that display spatial and temporal variability, but our understanding of these interactions is incomplete. Through investigating biomarkers of resistance and response, opportunities arise to discover new therapeutic targets and shape personalised treatment strategies. Here we review approved and emerging biomarkers of response to immune checkpoint inhibitors, in particular the recent rapid progress in host and tumour genomics. It is unlikely that a single biomarker will precisely predict response, but multivariate multiomic markers may provide a balanced assessment of these factors and more accurately identify patients who will benefit. Further efforts are required to translate these groundbreaking discoveries into novel therapeutics and biomarker driven clinical trials, to provide durable treatment response to a greater population of patients.

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