Cell fusion with type 2 macrophage induce heterogeneity of melanoma cells that potentiate immunological escape from cytotoxic T lymphocytes

ABSTRACT: Evasion from immunity is a major obstacle for achievement of successful cancer immunotherapy. Hybrids derived from cell-cell fusion is a theory associated with tumor heterogeneity and progression by conferring novel properties to tumor cells, such as drug resistance or metastatic capacity; however, its impact on immune evasion remains still unknown. Here, we investigated the potency of hybrids in immune evasion using tumor-macrophage hybrids. Hybrids were established by co-culture of a melanoma cell line, A375 and type 2 macrophages. The hybrids showed higher migration ability and higher tumorigenicity than those of the parental melanoma cells. We found that the hybrids were less sensitive to T cell receptor (TCR) specific for NY-ESO-1 transduced T cells (TCR-T cells) than parental melanoma cells, although hybrids and parental melanoma cells showed equivalent NY-ESO-1 expression. An in vitro tumor heterogeneity model revealed that TCR-T cells preferentially killed parental cells than hybrids and the survival rate of hybrids were higher than that in parental cells indicating hybrids evade from killing by TCR-T cells efficiently. A single cell analysis data set revealed that a few macrophage cells expressed melanoma differentiation antigens including gp100, MART-1 and tyrosinase, indicating hybrids exist in primary melanoma, and number of potential hybrids were corelated with poorer response to immune checkpoint blockade. These results provide evidence that melanoma-macrophage fusion has a role in tumor heterogeneity and immune evasion.

ORGANISM(S): Homo sapiens

PROVIDER: GSE210578 | GEO | 2023/05/04

REPOSITORIES: GEO