Association between PD1 mRNA and response to anti-PD1 monotherapy across multiple cancer types

Annals of Oncology : Official Journal of the European Society for Medical Oncology
Laia ParéAleix Prat

Abstract

We hypothesized that the abundance of PD1 mRNA in tumor samples might explain the differences in overall response rates (ORR) observed following anti-PD1 monotherapy across cancer types. RNASeqv2 data from 10 078 tumor samples representing 34 different cancer types was analyzed from TCGA. Eighteen immune-related gene signatures and 547 immune-related genes, including PD1, were explored. Correlations between each gene/signature and ORRs reported in the literature following anti-PD1 monotherapy were calculated. To translate the in silico findings to the clinical setting, we analyzed the expression of PD1 mRNA using the nCounter platform in 773 formalin-fixed paraffin embedded (FFPE) tumor samples across 17 cancer types. To test the direct relationship between PD1 mRNA, PDL1 immunohistochemistry (IHC), stromal tumor-infiltrating lymphocytes (sTILs) and ORR, we evaluated an independent FFPE-based dataset of 117 patients with advanced disease treated with anti-PD1 monotherapy. In pan-cancer TCGA, PD1 mRNA expression was found strongly correlated (r > 0.80) with CD8 T-cell genes and signatures and the proportion of PD1 mRNA-high tumors (80th percentile) within a given cancer type was variable (0%-84%). Strikingly, the PD1-high propor...Continue Reading

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Citations

Sep 16, 2018·Nature Reviews. Clinical Oncology·Peter Sidaway
Sep 20, 2019·Journal for Immunotherapy of Cancer·Swati GuptaDavid L Rimm
Aug 17, 2019·Cancers·Leire PedrosaJoan Maurel
Nov 12, 2020·ESMO Open·Alexios MatikasTheodoros Foukakis
Oct 27, 2020·Frontiers in Oncology·Evgeny N ImyanitovIlya V Tsimafeyeu
Apr 27, 2021·Expert Opinion on Emerging Drugs·Vineeth SukrithanBhavana Konda
May 1, 2021·Cancers·Natalia GeorgantzoglouStamatios Theocharis
May 30, 2021·Molecular Oncology·Fara Brasó-MaristanyAleix Prat
Jul 27, 2021·Frontiers in Immunology·Xiaohan ZhouDehua Wu
Jul 22, 2021·International Journal of General Medicine·Quan MengXiaobin Lin

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