作者
Aditi Sahu,Katsumi Kose,Lukas Kraehenbuehl,Candice Byers,Aliya Holland,Teguru Tembo,Anthony Santella,Anabel Alfonso,Madison Li,Miguel Córdova,Melissa Gill,Christi Alessi‐Fox,Salvador González,Piyush Kumar,Amber Weiching Wang,Nicholas R. Kurtansky,Pratik Chandrani,Shen Yin,Paras Mehta,Cristián Navarrete‐Dechent,Gary Peterson,Kimeil King,Stephen W. Dusza,Ning Yang,Shuaitong Liu,William T. Phillips,Pascale Guitera,Anthony Rossi,Allan C. Halpern,Liang Deng,Melissa Pulitzer,Ashfaq A. Marghoob,Chih-Shan Jason Chen,Taha Merghoub,Milind Rajadhyaksha
摘要
Response to immunotherapies can be variable and unpredictable. Pathology-based phenotyping of tumors into 'hot' and 'cold' is static, relying solely on T-cell infiltration in single-time single-site biopsies, resulting in suboptimal treatment response prediction. Dynamic vascular events (tumor angiogenesis, leukocyte trafficking) within tumor immune microenvironment (TiME) also influence anti-tumor immunity and treatment response. Here, we report dynamic cellular-level TiME phenotyping in vivo that combines inflammation profiles with vascular features through non-invasive reflectance confocal microscopic imaging. In skin cancer patients, we demonstrate three main TiME phenotypes that correlate with gene and protein expression, and response to toll-like receptor agonist immune-therapy. Notably, phenotypes with high inflammation associate with immunostimulatory signatures and those with high vasculature with angiogenic and endothelial anergy signatures. Moreover, phenotypes with high inflammation and low vasculature demonstrate the best treatment response. This non-invasive in vivo phenotyping approach integrating dynamic vasculature with inflammation serves as a reliable predictor of response to topical immune-therapy in patients.