Tumor-infiltrating immune cells (TIICs) play critical roles during the development and progression of cancers. However, only a few studies have investigated the niches of immune cells in melanoma using spatial transcriptomics, which may increase our mechanistic understanding of the immune phenotypic dynamics during tumor progression. Here, we aimed to elucidate the differential gene expression profiles of TIICs related to melanoma progression and to explore the intra-tumoral immune landscape. A formalin-fixed paraffin-embedded block was prepared with a single excision specimen from a patient with simultaneous multiple stages of melanoma in a single lesion, and profiled using spatial transcriptomics, with a focus on TIICs. We identified the heterogeneous composition and differential gene expression profiles of TIICs, especially in macrophages and T cells. As melanoma progressed, genes related to proinflammatory M1 macrophages, including GBP5 and CXCL9, were decreased. On the other hand, the expression of genes related to anti-inflammatory M2 macrophages including FN1, SERPINE2, and ID3 were significantly increased. In the case of T cells, genes related to T cell activation such as CCL19 and GZMK decreased, while genes such as FN1 and GPNMB, which inhibit T cell activation, significantly increased. Therefore, this study reveals the heterogeneity in immune cell composition and phenotypes as melanoma progresses. These results suggests that TIICs may play an important role in tumor progression and suggests their potential use as markers that can predict response or resistance to immunotherapy.

ESDR455 - Spatial transcriptomic analysis of tumor-infiltrating immune cells in melanoma reveals distinct immune profiles depending on tumor progression

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