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

Mark Yarchoan, Lee A. Albacker, Alexander C. Hopkins, Meagan Montesion, Karthikeyan Murugesan, Teena T. Vithayathil, Neeha Zaidi, Nilofer Azad, Daniel Laheru, Garrett M. Frampton, Elizabeth Jaffee

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number126908
JournalJCI Insight
Volume4
Issue number6
DOIs
StatePublished - Mar 21 2019

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Tumor Burden
Biomarkers
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

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Yarchoan, M., Albacker, L. A., Hopkins, A. C., Montesion, M., Murugesan, K., Vithayathil, T. T., ... Jaffee, E. (2019). PD-L1 expression and tumor mutational burden are independent biomarkers in most cancers. JCI Insight, 4(6), [126908]. https://doi.org/10.1172/jci.insight.126908

PD-L1 expression and tumor mutational burden are independent biomarkers in most cancers. / Yarchoan, Mark; Albacker, Lee A.; Hopkins, Alexander C.; Montesion, Meagan; Murugesan, Karthikeyan; Vithayathil, Teena T.; Zaidi, Neeha; Azad, Nilofer; Laheru, Daniel; Frampton, Garrett M.; Jaffee, Elizabeth.

In: JCI Insight, Vol. 4, No. 6, 126908, 21.03.2019.

Research output: Contribution to journalArticle

Yarchoan M, Albacker LA, Hopkins AC, Montesion M, Murugesan K, Vithayathil TT et al. PD-L1 expression and tumor mutational burden are independent biomarkers in most cancers. JCI Insight. 2019 Mar 21;4(6). 126908. https://doi.org/10.1172/jci.insight.126908
Yarchoan, Mark ; Albacker, Lee A. ; Hopkins, Alexander C. ; Montesion, Meagan ; Murugesan, Karthikeyan ; Vithayathil, Teena T. ; Zaidi, Neeha ; Azad, Nilofer ; Laheru, Daniel ; Frampton, Garrett M. ; Jaffee, Elizabeth. / PD-L1 expression and tumor mutational burden are independent biomarkers in most cancers. In: JCI Insight. 2019 ; Vol. 4, No. 6.
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