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Comprehensive single-cell immune profiling of tumor-infiltrating T lymphocytes in acral lentiginous melanoma with therapeutic implications.

ABSTRACT: Acral lentiginous melanoma (ALM) is the most common melanoma subtype in non-Caucasians. Despite significant advances in cancer immunotherapy, current immune checkpoint inhibitors remain unsatisfactory for ALM. Hence, we conducted a comprehensive immune profiling using single-cell RNA sequencing and single-cell T cell receptor (TCR) sequencing analysis, along with the reactivity screening of TCRs of tumor-infiltrating T lymphocytes (TILs) in ALM. We identified tumor-reactive CD8 T cell populations, primarily exhibiting an exhausted state, within multiple phenotypic subsets of TILs in ALM. In comparison to cutaneous melanoma, clusters with tumor-reactive phenotype presented a lower abundance, and enrichment of Treg cells were observed, suggesting suppressive immune microenvironment of ALM. We found a heterogeneous expression of co-inhibitory molecules in tumor-reactive CD8 TILs, with a subpopulation of activated T cells that was rich in genes related to cytotoxicity and marked by the expression of KLRC1 (NKG2A), a suppressive co-inhibitory molecule with therapeutic implications. Overall, our study provides a foundation for enhancing the efficacy of immunotherapy in ALM.

ORGANISM(S): Homo sapiens

PROVIDER: GSE242477 | GEO | 2023/09/06

REPOSITORIES: GEO

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