Wnt3a-expressing cancer stem cells impair CD8⁺ TRM function, contributing to immunotherapy resistance in Melanoma.

ABSTRACT: Immune checkpoint blockade (ICB) has revolutionized the treatment of advanced malignancies such as melanoma. However, a significant proportion of patients fail to respond, owing to mechanisms that remain poorly understood. Here, we developed murine melanoma cell lines (R1 and R2) derived from MO4 tumors and that are resistant to anti-PD-1 therapy. These resistant cells exhibited increased tumor initiation capacity in vivo correlating with enhanced spheroid formation in vitro, and greater invasiveness and metastatic potential in a lung macrometastasis model. Mechanistically, both R1- and R2- derived tumors showed enrichment of a cancer stem cell (CSC)-like population overexpressing Wnt3a, which correlated with reduced infiltration and impaired function of CD8⁺ tissu

SUBMITTER: Gajon JA 

PROVIDER: S-EPMC12688247 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature