Identification of a conserved subset of cold tumors responsive to immune checkpoint blockade
These studies indicate that loss of TGFβ signaling competency and gain of error-prone DNA repair identifies a subset of cold tumors that are responsive to ICB. Our mechanistic studies show that inhibiting TGFβ activity can convert a high βAlt, cold tumor into ICB-responsive tumors via NK cells. A biomarker consisting of combined TGFβ, DNA repair, and immune context signatures is a means to prospectively identify patients whose cancers may be converted from cold to hot with appropriate therapy.
Authors
- William Chou (ORCID: https://orcid.org/0000-0001-8957-3953)
- Matthew H. Spitzer (ORCID: https://orcid.org/0000-0002-5291-3819)
- Inés Guix
- Kobe Yuen (ORCID: https://orcid.org/0000-0001-8780-341X)
- Ann Lazar (ORCID: https://orcid.org/0000-0002-6341-0360)
- Mary Helen Barcellos‐Hoff (ORCID: https://orcid.org/0000-0002-5994-9558)
- Jade Moore (ORCID: https://orcid.org/0000-0001-8092-3363)
- Alexis J. Combes (ORCID: https://orcid.org/0000-0002-9110-6542)
- Jim Gkantalis
Institutions
- University of California, San Francisco (US)
- Gene Therapy Laboratory (FR)
Publication Details
- Journal
- Journal for ImmunoTherapy of Cancer
- Published
- 2025-03-01
- DOI
- https://doi.org/10.1136/jitc-2024-010528
- Citations
- 7
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 7.32
Funders
- Bristol-Myers Squibb
- Pfizer
- Astellas Pharma
- National Institutes of Health
- Genentech
- University of California, San Francisco
- National Cancer Institute