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Systematic investigation of chemo-immunotherapy synergism to shift anti-PD-1 resistance in cancer

Author

Listed:
  • Yue Wang

    (Department of Pharmaceutical Sciences, University of Pittsburgh)

  • Dhamotharan Pattarayan

    (Department of Pharmaceutical Sciences, University of Pittsburgh)

  • Haozhe Huang

    (Department of Pharmaceutical Sciences, University of Pittsburgh)

  • Yueshan Zhao

    (Department of Pharmaceutical Sciences, University of Pittsburgh)

  • Sihan Li

    (Department of Pharmaceutical Sciences, University of Pittsburgh)

  • Yifei Wang

    (Department of Pharmaceutical Sciences, University of Pittsburgh)

  • Min Zhang

    (Department of Pharmaceutical Sciences, University of Pittsburgh)

  • Song Li

    (Department of Pharmaceutical Sciences, University of Pittsburgh)

  • Da Yang

    (Department of Pharmaceutical Sciences, University of Pittsburgh
    University of Pittsburgh
    University of Pittsburgh)

Abstract

Chemo-immunotherapy combinations have been regarded as one of the most practical ways to improve immunotherapy response in cancer patients. In this study, we integrate the transcriptomics data from anti-PD-1-treated tumors and compound-treated cancer cell lines to systematically screen for chemo-immunotherapy synergisms in silico. Through analyzing anti-PD-1 induced expression changes in patient tumors, we develop a shift ability score to measure if a chemotherapy or a small molecule inhibitor treatment can shift anti-PD-1 resistance in tumor cells. By applying shift ability analysis to 41,321 compounds and 16,853 shRNA treated cancer cell lines transcriptomic data, we characterize the landscape of chemo-immunotherapy synergism and experimentally validated a mitochondrial RNA-dependent mechanism for drug-induced immune activation in tumor. Our study represents an effort to mechanistically characterize chemo-immunotherapy synergism and will facilitate future pre-clinical and clinical studies.

Suggested Citation

  • Yue Wang & Dhamotharan Pattarayan & Haozhe Huang & Yueshan Zhao & Sihan Li & Yifei Wang & Min Zhang & Song Li & Da Yang, 2024. "Systematic investigation of chemo-immunotherapy synergism to shift anti-PD-1 resistance in cancer," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47433-y
    DOI: 10.1038/s41467-024-47433-y
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