Abstract
Purpose: PD-1/L1 axis-directed therapies produce clinical responses in a subset of patients; therefore, biomarkers of response are needed. We hypothesized that quantifying key immunosuppression mechanisms within the tumor microenvironment by multiparameter algorithms would identify strong predictors of anti-PD-1 response.Experimental Design: Pretreatment tumor biopsies from 166 patients treated with anti-PD-1 across 10 academic cancer centers were fluorescently stained with multiple markers in discovery (n = 24) and validation (n = 142) cohorts. Biomarker-positive cells and their colocalization were spatially profiled in pathologist-selected tumor regions using novel Automated Quantitative Analysis algorithms. Selected biomarker signatures, PD-1/PD-L1 interaction score, and IDO-1/HLA-DR coexpression were evaluated for anti-PD-1 treatment outcomes.Results: In the discovery cohort, PD-1/PD-L1 interaction score and/or IDO-1/HLA-DR coexpression was strongly associated with anti-PD-1 response (P = 0.0005). In contrast, individual biomarkers (PD-1, PD-L1, IDO-1, HLA-DR) were not associated with response or survival. This finding was replicated in an independent validation cohort: patients with high PD-1/PD-L1 and/or IDO-1/HLA-DR were...Continue Reading
Citations
Nov 27, 2018·Expert Review of Anticancer Therapy·Qiwei ChenQuanlin Li
Jun 20, 2019·Diagnostics·Yang-Yi ChenPo-Lin Kuo
Apr 18, 2020·Cancer Communications·Wei Chang Colin TanTony Kiat Hon Lim
Nov 13, 2019·Archives of Pathology & Laboratory Medicine·Eric E WalkUNKNOWN College of American Pathologists Personalized Health Care Committee
Mar 2, 2019·Cancers·Paul HofmanMarius Ilié
May 23, 2019·Journal for Immunotherapy of Cancer·Davide BedognettiUNKNOWN Society for Immunotherapy of Cancer (SITC) Cancer Immune Responsiveness Task Force and Working Groups
Sep 12, 2020·Journal for Immunotherapy of Cancer·Alexandra FrazaoAnne Caignard
May 28, 2020·Frontiers in Immunology·Florent PetitprezWolf H Fridman
Jan 23, 2019·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Ling LiKen H Young
Apr 23, 2020·Genes·Xuanyi WangBo Li
Feb 1, 2020·Oncoimmunology·Tuba N GideJames S Wilmott
Jun 27, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Dmitriy ZamarinDavid S Hong
Nov 23, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Margaret L AxelrodJustin M Balko
Jan 15, 2021·Scientific Reports·A Casasola-LaMacchiaH Neubert
Jan 15, 2021·Scientific Reports·Rong-Zhi HuangXu Li
Aug 29, 2020·Cancer Research·Lissete Sánchez-MagranerBanafshé Larijani
Apr 4, 2021·Cancers·Eileen ShiuanKathryn E Beckermann
Apr 13, 2021·Frontiers in Oncology·Laura GadeyneFrancesca Maria Bosisio
May 1, 2021·Cancers·Mattia GaruttiFabio Puglisi
Jul 17, 2021·Journal for Immunotherapy of Cancer·Janis M TaubeCliff Hoyt
Mar 24, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yana G NajjarAhmad A Tarhini
Jun 11, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jan C BraseAlexander Roesch
Jun 11, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jodi M CarterMatthew P Goetz
Feb 26, 2020·Neuroendocrinology·David J PinatoRohini Sharma
Oct 24, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Niki GavrielatouDavid L Rimm
Nov 18, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Isabelle GiraultCaroline Robert