 Tumor histoculture captures the dynamic interactions between tumor and immune components in response to anti-PD1 in head and neck cancerNandini 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 and
Satish Sankaran ()
Nature Communications, 2024, vol. 15, issue 1, 1-15 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. Date: 2024 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45723-z Ordering information: This journal article can be ordered from DOI: 10.1038/s41467-024-45723-z Access Statistics for this article Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie More articles in Nature Communications from Nature |
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