The role of tissue-resident memory T cells as mediators for response and toxicity in immunotherapy-treated melanoma-two sides of the same coin?

组织驻留记忆T细胞在免疫疗法治疗黑色素瘤中作为反应和毒性介质的作用——是同一枚硬币的两面吗?

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Abstract

Tissue-resident memory T cells (T(RM) cells) have become an interesting subject of study for antitumor immunity in melanoma and other solid tumors. In the initial phases of antitumor immunity, they maintain an immune equilibrium and protect against challenges with tumor cells and the formation of primary melanomas. In metastatic settings, they are a prime target cell population for immune checkpoint inhibition (ICI) because they highly express inhibitory checkpoint molecules such as PD-1, CTLA-4, or LAG-3. Once melanoma patients are treated with ICI, T(RM) cells residing in the tumor are reactivated and expand. Tumor killing is achieved by secreting effector molecules such as IFN-γ. However, off-target effects are also observed. Immune-related adverse events, such as those affecting barrier organs like the skin, can be mediated by ICI-induced T(RM) cells. Therefore, a detailed understanding of this memory T-cell type is obligatory to better guide and improve immunotherapy regimens.

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