Tumor histoculture captures the dynamic interactions between tumor and immune components in response to anti-PD1 in head and neck cancer.
Nat Commun
; 15(1): 1585, 2024 Feb 21.
Article
in En
| MEDLINE
| ID: mdl-38383563
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Head and Neck Neoplasms
Limits:
Humans
Language:
En
Journal:
Nat Commun
Year:
2024
Document type:
Article