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

Author

Listed:
  • Nandini Pal Basak

    (Farcast Biosciences India Pvt. Ltd)

  • Kowshik Jaganathan

    (Farcast Biosciences India Pvt. Ltd)

  • Biswajit Das

    (Farcast Biosciences India Pvt. Ltd)

  • Oliyarasi Muthusamy

    (Farcast Biosciences India Pvt. Ltd)

  • Rajashekar M

    (Farcast Biosciences India Pvt. Ltd)

  • Ritu Malhotra

    (Farcast Biosciences India Pvt. Ltd)

  • Amit Samal

    (Farcast Biosciences India Pvt. Ltd)

  • Moumita Nath

    (Farcast Biosciences India Pvt. Ltd)

  • Ganesh MS

    (Vydehi Institute of Medical Sciences & Research Centre)

  • Amritha Prabha Shankar

    (Vydehi Institute of Medical Sciences & Research Centre)

  • Prakash BV

    (Sri Lakshmi Multi-Speciality Hospital)

  • Vijay Pillai

    (Mazumdar Shaw Medical Center, Narayana Health)

  • Manjula BV

    (Bangalore Baptist Hospital)

  • Jayaprakash C

    (DBR & SK Super Speciality Hospital)

  • Vasanth K

    (Farcast Biosciences India Pvt. Ltd)

  • Gowri Shankar K

    (Farcast Biosciences India Pvt. Ltd)

  • Sindhu Govindan

    (Farcast Biosciences India Pvt. Ltd)

  • Syamkumar V

    (Farcast Biosciences India Pvt. Ltd)

  • Juby

    (Farcast Biosciences India Pvt. Ltd)

  • Koushika R

    (Farcast Biosciences India Pvt. Ltd)

  • Chandan Bhowal

    (Farcast Biosciences India Pvt. Ltd)

  • Upendra Kumar

    (Farcast Biosciences India Pvt. Ltd)

  • Govindaraj K

    (Farcast Biosciences India Pvt. Ltd)

  • Mohit Malhotra

    (Farcast Biosciences India Pvt. Ltd)

  • Satish Sankaran

    (Farcast Biosciences India Pvt. Ltd)

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.

Suggested Citation

  • 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 , 2024. "Tumor histoculture captures the dynamic interactions between tumor and immune components in response to anti-PD1 in head and neck cancer," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45723-z
    DOI: 10.1038/s41467-024-45723-z
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    References listed on IDEAS

    as
    1. Chia-Chin Wu & Y. Alan Wang & J. Andrew Livingston & Jianhua Zhang & P. Andrew Futreal, 2022. "Prediction of biomarkers and therapeutic combinations for anti-PD-1 immunotherapy using the global gene network association," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Caroline Robert, 2020. "A decade of immune-checkpoint inhibitors in cancer therapy," Nature Communications, Nature, vol. 11(1), pages 1-3, December.
    3. Dora Hammerl & John W. M. Martens & Mieke Timmermans & Marcel Smid & Anita M. Trapman-Jansen & Renée Foekens & Olga I. Isaeva & Leonie Voorwerk & Hayri E. Balcioglu & Rebecca Wijers & Iris Nederlof & , 2021. "Spatial immunophenotypes predict response to anti-PD1 treatment and capture distinct paths of T cell evasion in triple negative breast cancer," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    4. Susan P. Foy & Kyle Jacoby & Daniela A. Bota & Theresa Hunter & Zheng Pan & Eric Stawiski & Yan Ma & William Lu & Songming Peng & Clifford L. Wang & Benjamin Yuen & Olivier Dalmas & Katharine Heeringa, 2023. "Non-viral precision T cell receptor replacement for personalized cell therapy," Nature, Nature, vol. 615(7953), pages 687-696, March.
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