Immunoprofiling at an Institutional Scale Reveals That High Numbers of Intratumoral CD8 + and PD-1 + Cells Predict Superior Patient Survival Across Major Cancer Types Independent of Major Risk Factors

作者：Joao V. Alessi, James R. Lindsay, Anita Giobbie‐Hurder, Bijaya Sharma, Kristen D. Felt, Priti Kumari, Tali Mazor, Ethan G Cerami, William E. Lotter, Jennifer Altreuter, Jason L. Weirather, Ian D. Dryg, Katharina Hoebel, Michael P. Manos, Elio Adib, Jennifer D. Curtis, Biagio Ricciuti, Alessandro Di Federico, Fatme Ghandour, Eddy Saad, Xinan Wang, Federica Pecci, Marta M. Holovatska, Malini Marion Gandhi, Melissa E. Hughes, Tess A. O’Meara, Sabrina J. Chan, Kathleen Lindahl Pfaff, Panagiotis A. Konstantinopoulos, Frank S. Hodi, Margaret Ann Shipp, Sabina Signoretti, Toni K. Choueiri, Xiao X. Wei, Sandro Santagata, Glenn J. Hanna, Nancy U. Lin, Sara M. Tolaney, Joyce F. Liu, Peter Karl Sorger, Neal Ian Lindeman, Lynette Marie Sholl, Jonathan Andrew Nowak, David Allen Barbie, Mark Magdi Awad, Bruce Evan Johnson, Scott J. Rodig · 发表于：JCO Precision Oncology · 年份：2025 · DOI：10.1200/po-25-00240 · 被引用次数：10 · 研究领域：Cancer Immunotherapy and Biomarkers、Immune cells in cancer、Inflammatory Biomarkers in Disease Prognosis

PURPOSE Retrospective studies have found associations between the number of intratumoral immune cells and patient outcomes for specific cancers treated with targeted therapies. However, the clinical value of routinely quantifying intratumoral immune biomarkers using a digital pathology platform in the pan-cancer setting within an active clinical laboratory has not been established. METHODS We developed ImmunoProfile, a daily clinical workflow that integrates automated multiplex immunofluorescence tissue staining, digital slide imaging, and machine learning–assisted scoring to quantify intratumoral CD8 + , PD-1 + , CD8 + PD-1 + , and FOXP3 + immune cells and PD-L1 expression in formalin-fixed, paraffin-embedded tissue samples in a standardized and reproducible manner. We prospectively applied ImmunoProfile to biopsies collected from 2,023 unselected patients with cancer over a 3-year period in the clinical laboratory and correlated the results with patient survival. RESULTS In the pan-cancer cohort, patients with high numbers of intratumoral CD8 + or PD-1 + cells in had significantly lower risks of death compared with those with low numbers (CD8 + : high v low hazard ratio [HR], 0.62 [95% CI, 0.48 to 0.81], Wald P = .002; PD-1 + : high v low HR, 0.65 [95% CI, 0.51 to 0.83]; P = .0009) after adjusting for risk factors, including cancer type. In subset analyses, patients with high numbers of intratumoral CD8 + , PD-1 + , and/or CD8 + PD-1 + cells showed lower risks of death from...