학술논문
Tumor histoculture captures the dynamic interactions between tumor and immune components in response to anti-PD1 in head and neck cancer
Document Type
article
Author
Nandini Pal Basak; Kowshik Jaganathan; Biswajit Das; Oliyarasi Muthusamy; Rajashekar M; Ritu Malhotra; Amit Samal; Moumita Nath; Ganesh MS; Amritha Prabha Shankar; Prakash BV; Vijay Pillai; Manjula BV; Jayaprakash C; Vasanth K; Gowri Shankar K; Sindhu Govindan; Syamkumar V; Juby; Koushika R; Chandan Bhowal; Upendra Kumar; Govindaraj K; Mohit Malhotra; Satish Sankaran
Source
Nature Communications, Vol 15, Iss 1, Pp 1-15 (2024)
Subject
Language
English
ISSN
2041-1723
65214595
65214595
Abstract
Abstract Dynamic interactions within the tumor micro-environment drive patient response to immune checkpoint inhibitors. Existing preclinical models lack true representation of this complexity. Using a Head and Neck cancer patient derived TruTumor histoculture platform, the response spectrum of 70 patients to anti-PD1 treatment is investigated in this study. With a subset of 55 patient samples, multiple assays to characterize T-cell reinvigoration and tumor cytotoxicity are performed. Based on levels of these two response parameters, patients are stratified into five sub-cohorts, with the best responder and non-responder sub-cohorts falling at extreme ends of the spectrum. The responder sub-cohort exhibits high T-cell reinvigoration, high tumor cytotoxicity with T-cells homing into the tumor upon treatment whereas immune suppression and tumor progression pathways are pre-dominant in the non-responders. Some moderate responders benefit from combination of anti-CTLA4 with anti-PD1, which is evident from better cytotoxic T-cell: T-regulatory cell ratio and enhancement of tumor cytotoxicity. Baseline and on-treatment gene expression signatures from this study stratify responders and non-responders in unrelated clinical datasets.