免疫疗法
医学
免疫分型
癌症免疫疗法
癌症
生物标志物
免疫系统
肺癌
肿瘤科
内科学
免疫学
抗原
生物
生物化学
作者
Xiao Li,Jeffrey Eastham,Jennifer M. Giltnane,W. Zou,Andries Zijlstra,Evgeniy Tabatsky,Romain Banchereau,Ching‐Wei Chang,Barzin Y. Nabet,Namrata S. Patil,Luciana Molinero,Steve Chui,Maureen Peterson,Shari Lau,Linda Rangell,Yannick Waumans,Mark Kockx,Darya Orlova,Hartmut Koeppen
标识
DOI:10.1101/2023.04.03.535467
摘要
Abstract Background Cancer immunotherapy has transformed the clinical approach to patients with malignancies as profound benefits can be seen in a subset of patients. To identify this subset, biomarker analyses increasingly focus on phenotypic and functional evaluation of the tumor microenvironment (TME) to determine if density, spatial distribution, and cellular composition of immune cell infiltrates can provide prognostic and/or predictive information. Attempts have been made to develop standardized methods to evaluate immune infiltrates in the routine assessment of certain tumor types; however, broad adoption of this approach in clinical decision-making is still missing. Methods We developed approaches to categorize solid tumors into “Desert”, “Excluded” and “Inflamed” types according to the spatial distribution of CD8+ immune effector cells to determine the prognostic and/or predictive implications of such labels. To overcome the limitations of this subjective approach we incrementally developed four automated analysis pipelines of increasing granularity and complexity for density and pattern assessment of immune effector cells. Results We show that categorization based on “manual” observation is predictive for clinical benefit from anti-programmed cell death ligand-1 (PD-L1) therapy in two large cohorts of patients with non-small cell lung cancer (NSCLC) or triple-negative breast cancer (TNBC). For the automated analysis we demonstrate that a combined approach outperforms individual pipelines and successfully relates spatial features to pathologist-based read-outs and patient response to therapy. Conclusions Our findings suggest tumor immunophenotype (IP) generated by automated analysis pipelines should be evaluated further as potential predictive biomarkers for cancer immunotherapy. What is already known on this topic Clinical benefit from checkpoint inhibitor-targeted therapies is realized only in a subset of patients. Robust biomarkers to identify patients who may respond to such therapies are needed. What this study adds We have developed manual and automated approaches to categorize tumors into immunophenotypes based on the spatial distribution of CD8+ T effector cells that predict clinical benefit from anti-PD-L1 immunotherapy for patients with advanced non-small cell lung cancer or triple-negative breast cancer. How this study might affect research, practice or policy Tumor immunophenotypes should be further validated as predictive biomarker for checkpoint inhibitor-targeted therapies in prospective clinical studies.
科研通智能强力驱动
Strongly Powered by AbleSci AI