Tumor histoculture captures the dynamic interactions between tumor and immune components in response to anti-PD1 in head and neck cancer
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Updated: Jul 2, 2025
Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
Published on: March 7, 2025
Nandini Pal Basak1, Kowshik Jaganathan1, Biswajit Das1
1Farcast Biosciences India Pvt. Ltd, Bangalore, Karnataka, India.
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.
Insights
This study uses a patient-derived Head and Neck cancer model to analyze responses to anti-PD1 immunotherapy. Findings reveal distinct patient subgroups based on T-cell activity and tumor killing, aiding personalized treatment strategies.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Tumor micro-environment dynamics critically influence immune checkpoint inhibitor efficacy.
- Current preclinical models often fail to capture the complexity of patient responses.
- Head and Neck cancer patients exhibit a wide spectrum of responses to anti-PD1 therapy.
Purpose of the Study:
- To investigate the response spectrum of Head and Neck cancer patients to anti-PD1 treatment using a patient-derived histoculture platform.
- To characterize T-cell reinvigoration and tumor cytotoxicity in response to immunotherapy.
- To stratify patients into distinct response sub-cohorts based on immune and tumor parameters.
Main Methods:
- Utilized a Head and Neck cancer patient-derived TruTumor histoculture platform for 70 patients.
- Performed assays on 55 patient samples to assess T-cell reinvigoration and tumor cytotoxicity.
- Stratified patients into five sub-cohorts based on response parameters and analyzed gene expression signatures.
Main Results:
- Identified distinct responder and non-responder sub-cohorts with varying T-cell activity and tumor cytotoxicity.
- Responders showed high T-cell reinvigoration and tumor infiltration, while non-responders exhibited immune suppression.
- Combination therapy (anti-CTLA4 with anti-PD1) showed benefit in moderate responders by improving cytotoxic T-cell to T-regulatory cell ratios.
- Baseline and on-treatment gene expression signatures successfully stratified responders and non-responders in independent datasets.
Conclusions:
- Patient-derived histoculture models provide valuable insights into anti-PD1 response heterogeneity.
- T-cell reinvigoration and tumor cytotoxicity are key determinants of treatment efficacy.
- Gene expression signatures can predict patient response to immune checkpoint inhibitors, enabling personalized treatment approaches.
