Data from Neoantigen targetability in progressive advanced melanoma

Abstract Purpose: The availability of (neo)antigens and the infiltration of tumors by (neo)antigen-specific T cells are crucial factors in cancer immunotherapy. In this study, we aimed to investigate the targetability of (neo)antigens in advanced progessive melanoma and explore the potential for continued T cell-based immunotherapy. Experimental Design: We examined a cohort of eight melanoma patients who had sequential metastases resected at early and later time points. Antigen presenting capacity was assessed using immunohistochemistry and flow cytometry. T cell infiltration was quantified through multiplex immunofluorescence. Whole-exome and RNA sequencing were conducted to identify neoantigens and assess the expression of neoantigens and tumor-associated antigens. Mass spectrometry was employed to evaluate antigen presentation. Tumor recognition by autologous T cells was assessed by coculture assays with cell lines derived from the metastatic lesions. Results: We observed similar T cell infiltration in paired early and later metastatic lesions. While elements of the antigen presenting machinery were affected in some later metastatic lesions, both the early and later metastasis-derived cell lines were recognized by autologous T cells. At the genomic level, the (neo)antigen landscape was dynamic, but the (neo)antigen load was stable between paired lesions. Conclusions: Our findings indicate that subsequently isolated tumors from late-stage melanoma patients retain sufficient antigen presenting capacity, T cell infiltration, and a stable (neo)antigen load, allowing recognition of tumor cells by T cells. This indicates a continuous availability of T cell targets in metastases occurring at different time points and supports further exploration of neoantigen-specific T cell-based therapeutic approaches for advanced melanoma.