XPC deficiency is associated with accelerate melanoma growth and increased regulatory T-cell frequencies

Xeroderma pigmentosum complementation group C (XPC) is a protein that recognizes helix-distorting DNA lesions and initiates the global genome branch of nucleotide excision repair (NER). Its absence favors lesion persistence and mutation accumulation, increasing skin cancer susceptibility (Cancer Res. (2000) 60:1580). Regulatory T cells (Tregs) can favor skin tumor establishment (J. Immunother. Cancer (2025) 13:e013118), and and a relationship between increased T reg frequency in XPC -/- mice has already been observed (Nat. Commun. (2026) 17:3157). We assessed how XPC absence affects melanoma progression, focusing on T cell alterations. B16-F10 melanoma cells were grown in high-glucose Dulbecco's modified Eagle medium to approximately 90% confluence. Wild-type and Xpc-/- C57BL/6 mice received 5×10⁵ cells subcutaneously in the right flank. Tumor growth was monitored for 15 days; tumor volume was calculated by ellipsoid formula 0.52×width²×length. On day 15, mices were euthanized; tumors were weighed and processed to isolate tumor-infiltrating lymphocytes, and inguinal tumor-draining lymph nodes were collected. T-cell phenotypes were assessed by flow cytometry. Compared with wild-type mice, Xpc-/- mice had faster tumor growth and greater tumor volumes (p<0.05), higher CD4⁺Foxp3⁺ Treg frequencies in tumors and lymph nodes (p<0.05), and lower intratumoral CD8⁺ T-cell frequency. Programmed cell death protein 1 (PD-1) expression was higher on lymph node Tregs. Th1 transcription factor T-bet expression was higher in CD4⁺Foxp3^- and CD8⁺ T cells in both compartments. These findings associate XPC deficiency to Treg enrichment, reduced intratumoral CD8⁺ T-cell frequency and accelerated melanoma growth, supporting the hypothesis of a regulatory immune environment permissive to tumor progression. Increased T-bet expression coexisted with this phenotype; functional studies are needed to clarify how regulatory and effector responses contribute to tumor control.