Xevinapant plus Chemoradiotherapy Negatively Sculpts the Tumor-Immune Microenvironment in Head and Neck Cancer
Despite hugely promising randomized phase II study data, combined CRT plus xevinapant failed in the TrilynX phase III clinical trial in locally advanced SCCHN. We show that adding xevinapant to chemoradiotherapy in vivo dysregulates antitumor lymphocyte function, acute-phase proteins, and cell death pathways, with net immunosuppressive effects on the tumor-immune microenvironment.
Authors
- Victoria Roulstone (ORCID: https://orcid.org/0000-0003-4141-8123)
- Elizabeth S. Appleton (ORCID: https://orcid.org/0000-0002-8794-3428)
- Joan Kyula (ORCID: https://orcid.org/0000-0002-9299-0544)
- Jyoti S. Choudhary (ORCID: https://orcid.org/0000-0003-0881-5477)
- Charleen Chan Wah Hak (ORCID: https://orcid.org/0000-0002-6386-5699)
- Emmanuel Christian Patin (ORCID: https://orcid.org/0000-0001-5390-5733)
- Lisa C. Hubbard (ORCID: https://orcid.org/0009-0007-1540-4445)
- Antonio Rullan (ORCID: https://orcid.org/0000-0002-7365-9629)
- Amarin Wongariyapak (ORCID: https://orcid.org/0009-0009-3867-1022)
- Zuza Kozik (ORCID: https://orcid.org/0000-0001-6713-5776)
- Shane Foo (ORCID: https://orcid.org/0000-0001-6295-7404)
- Holly Baldock (ORCID: https://orcid.org/0000-0003-2751-4549)
- Malin Pedersen (ORCID: https://orcid.org/0000-0003-1887-733X)
- Annalisa Nicastri (ORCID: https://orcid.org/0000-0002-1895-0317)
- Tencho Tenev (ORCID: https://orcid.org/0000-0001-8762-1069)
- Alan A. Melcher (ORCID: https://orcid.org/0000-0002-2042-3380)
- Valentina Gifford (ORCID: https://orcid.org/0000-0002-6612-7034)
- Kevin Joseph Harrington (ORCID: https://orcid.org/0000-0002-6014-348X)
- Masahiro Ono (ORCID: https://orcid.org/0000-0002-9284-7326)
- Anton Patrikeev (ORCID: https://orcid.org/0009-0000-0638-8390)
Institutions
- Institute of Cancer Research (GB)
- Breast Cancer Now (GB)
- Cancer Research UK (GB)
- Cancer Services (US)
- University College London (GB)
- Imperial College London (GB)
Publication Details
- Journal
- Cancer Research Communications
- Published
- 2025-10-22
- DOI
- https://doi.org/10.1158/2767-9764.crc-25-0604
- Citations
- 1
- Primary Topic
- RNA Interference and Gene Delivery
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Wellcome Trust
- Cancer Research UK
- National Institute for Health and Care Research