Effects of Vemurafenib ± Cobimetinib on Intratumoral and Host Immunity in Patients With BRAFV600 Mutant Melanoma: Implications for Combination With Immunotherapy.

ABSTRACT:

Background

Prior studies in patients with BRAF-mutant melanoma have shown increased density of tumor infiltrating lymphocytes (TIL) after 2 weeks of BRAF (BRAFi) ± MEK inhibition (MEKi), but did not characterize the functional state or clonal diversity of TIL over time. We evaluated sequential tumor biopsies during therapy to test the hypotheses that BRAF/MEKi would increase TIL to day 29, with increases in IFNγ signatures and T-cell homing receptor ligands and expansion of functional intratumoral tumor-reactive CD8 T-cells and TIL clonality in the tumor microenvironment.

Methods

Subjects with biopsy-accessible BRAF-mutant advanced melanoma received vemurafenib+/-cobimetinib. Tumor biopsies were obtained at baseline and days 8, 15, and 29 on therapy. Tumors were analyzed by

SUBMITTER: Rapisuwon S 

PROVIDER: S-EPMC12789045 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature