Journal Article

Tumor histoculture captures the dynamic interactions between tumor and immune components in response to anti-PD1 in head and neck cancer

Malhotra, Ritu, Govindan, Sindhu, K, Vasanth, Nath, Moumita, K, Gowri Shankar, Bhowal, Chandan, Malhotra, Mohit, Samal, Amit, MS, Ganesh, R, Koushika, C, Jayaprakash, Juby, BV, Manjula, K, Govindaraj, V, Syamkumar, M, Rajashekar, BV, Prakash, Basak, Nandini Pal, Jaganathan, Kowshik, Muthusamy, Oliyarasi, Kumar, Upendra, Shankar, Amritha Prabha, Das, Biswajit, Pillai, Vijay, Sankaran, Satish

2024

Overview

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. Tumor histocultures have been exploited as tools to predict response to cancer therapy. Here the authors report the development and testing of a tumor histoculture platform to study response to immune checkpoint inhibitors in head and neck squamous cell carcinoma.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/106 / 13/21 / 13/31 / 13/51 / 38/39 / 692/4028/67/1536 / 692/4028/67/580 / 692/4028/67/70 / Cancer / Cancer therapies / CTLA-4 protein / Cytotoxicity / Gene expression / Head & neck cancer / Head and neck carcinoma / Humanities and Social Sciences / Immune checkpoint inhibitors / Inhibitors / Lymphocytes T / multidisciplinary / Patients / PD-1 protein / Science / Science (multidisciplinary) / Squamous cell carcinoma / Toxicity / Tumors