Combined treatment with CDK4/6, CDK2, and CXCR1/2 inhibitors effectively halts the growth of BRAF wild-type melanoma tumors
The combination of all three inhibitors resulted in a tumor microenvironment characterized by increased IFNγ-producing CD4+ T cells, decreased CD4+FOXP3+ T regulatory cells (Tregs), and decreased IL-10-producing CD4+ T cells. This combination also decreased the percentage of CD8+ T cells that expressed PD-1 or TIM-3 and increased the ratio of MHCII+F4/80+ M1-like macrophages to CD206+F4/80+ M2-like macrophages. These data suggest that inhibiting CDK4/6 and CDK2, combined with antagonism of CXCR1/2, may be an effective treatment for BRAF wild-type melanoma tumors and NRAS mutant melanoma tumors that express Rb and are resistant to immune checkpoint inhibitors.
Authors
- Chi Yan (ORCID: https://orcid.org/0000-0002-8658-7302)
- Ann Richmond (ORCID: https://orcid.org/0000-0002-9580-900X)
- Weifeng Luo (ORCID: https://orcid.org/0000-0002-0426-2951)
- Dean Y. Maeda (ORCID: https://orcid.org/0000-0002-9304-6846)
- Sheau‐Chiann Chen (ORCID: https://orcid.org/0000-0002-5574-1434)
- John A. Zebala (ORCID: https://orcid.org/0000-0002-3581-6750)
- Jinming Yang (ORCID: https://orcid.org/0000-0002-8703-0493)
- Patricia A. Ward
Institutions
- Vanderbilt University (US)
- CancerCare Manitoba (CA)
- VA Tennessee Valley Healthcare System (US)
- Syntrix Biosystems (United States) (US)
- Research Institute in Oncology and Hematology (CA)
- University of Manitoba (CA)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Frontiers in Oncology
- Published
- 2025-08-19
- DOI
- https://doi.org/10.3389/fonc.2025.1609735
- Citations
- 3
- Primary Topic
- Advanced Breast Cancer Therapies
- Type
- article
- Field-Weighted Citation Impact
- 4.56
Funders
- U.S. Department of Veterans Affairs
- National Cancer Institute