4.7 Article

PD-L1 expression and tumor mutational burden are independent biomarkers in most cancers

Journal

JCI INSIGHT
Volume 4, Issue 6, Pages -

Publisher

AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.126908

Keywords

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Funding

  1. Foundation Medicine Inc.
  2. Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy
  3. Viragh Foundation
  4. National Cancer Institute Specialized Program of Research Excellence (SPORE) in Gastrointestinal Cancers [P50 CA062924]
  5. NIH Center Core Grant [P30 CA006973]
  6. Norman & Ruth Rales Foundation
  7. Conquer Cancer Foundation

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BACKGROUND. PD-L1 expression and tumor mutational burden (TMB) have emerged as important biomarkers of response to immune checkpoint inhibitor (ICI) therapy. These biomarkers have each succeeded and failed in predicting responders for different cancer types. We sought to describe the PD-L1 expression landscape across the spectrum of ICI-responsive human cancers, and to determine the relationship between PD-L1 expression, TMB, and response rates to ICIs. METHODS. We assessed 9887 clinical samples for PD-L1 expression and TMB. RESULTS. PD-L1 expression and TMB are not significantly correlated within most cancer subtypes, and they show only a marginal association at the tumor sample level (Pearson's correlation 0.084). Across distinct tumor types, PD-L1 expression and TMB have nonoverlapping effects on the response rate to PD-1/PD-L1 inhibitors and can broadly be used to categorize the immunologic subtypes of cancer. CONCLUSION. Our results indicate that PD-L1 expression and TMB may each inform the use of ICIs, point to different mechanisms by which PD-L1 expression regulates ICI responsiveness, and identify new opportunities for therapeutic development.

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