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Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy

Suzanne L Topalian1, Janis M Taube2,3,4, Robert A Anders4

  • 1Department of Surgery, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy, 1550 Orleans Street, CRB2 Room 508, Baltimore, Maryland 21287, USA.

Nature Reviews. Cancer
|April 16, 2016
PubMed

Insights

Biomarkers are crucial for optimizing immune checkpoint inhibitor therapies like anti-PD1 and anti-CTLA4. Research is exploring immunological, genetic, and virological factors to predict patient responses and guide combination treatments.

Area of Science:

  • Immunology and Cancer Therapeutics
  • Biomarker Discovery in Oncology

Background:

  • Recent approvals of immune checkpoint inhibitors targeting CTLA4 and PD1 have transformed cancer treatment for melanoma, lung, and kidney cancers.
  • Despite therapeutic advances, optimal clinical use and prediction of treatment outcomes for these drugs remain significant challenges.
  • The development of companion diagnostics, such as PDL1 tests, underscores the critical need for predictive biomarkers.

Purpose of the Study:

  • To review and discuss biomarkers relevant to anti-PD1 therapy.
  • To explore the distinct biomarker development requirements for CTLA4 compared to PD1.
  • To highlight how mechanism-based insights can inform novel synergistic treatment strategies.

Main Methods:

  • Discussion of immunological criteria for anti-PD1 biomarker development.
  • Exploration of genetic factors influencing response to immune checkpoint blockade.
  • Analysis of virological markers in the context of anti-PD1 therapy.

Main Results:

  • Identified key immunological, genetic, and virological criteria for predicting anti-PD1 therapy efficacy.
  • Emphasized the differential biological mechanisms of CTLA4 and PD1, necessitating tailored biomarker approaches.
  • Provided insights into potential synergistic combinations based on understanding immune checkpoint blockade mechanisms.

Conclusions:

  • Biomarker definition is essential for refining the clinical application of immune checkpoint inhibitors.
  • Tailored biomarker strategies are required for different immune checkpoints like PD1 and CTLA4.
  • Mechanism-driven research can facilitate the development of more effective combination immunotherapies.

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