人类皮肤转移性黑色素瘤是最致命的皮肤癌症。偶尔可以观察到部分或不完全的自发性消退，主要通过T细胞介导。然而，其潜在机制尚未完全揭示。我们在自发性消退的切除性黑色素瘤中进行了首次免疫应答的研究，该研究在梨贝乔夫迷你猪皮肤黑色素瘤（MeLiM）模型中进行，这是一种独特的猪皮肤黑色素瘤模型。利用多参数流式细胞术和整合新的临床和组织学回归标准，我们发现T细胞和B细胞仅存在于晚期，这表明它们在恶性细胞初始破坏中的作用不大。NK细胞在T细胞之前浸润肿瘤，因此可能参与诱导回归过程。无论回归阶段如何，粒细胞是肿瘤微环境中主要的免疫细胞群集。在这些细胞中，MHCII+ CD163-巨噬细胞在数量上与其他肿瘤相关巨噬细胞有明显的表型和功能差异，并且在首次回归迹象出现时增加，这表明它们在启动回归过程中起到至关重要的作用。我们的研究支持巨噬细胞重编程在人类中的重要性，以改善转移性黑色素瘤的免疫治疗方法。© 2023. 作者。

The human cutaneous metastatic melanoma is the deadliest skin cancer. Partial, or less frequently complete spontaneous regressions could be observed, mainly mediated by T cells. Nevertheless, the underlying mechanisms are not fully unraveled. We investigated the first events of the immune response related to cancer regression in Melanoma-bearing Libechov Minipigs (MeLiM), a unique swine model of cutaneous melanoma that regresses spontaneously. Using a multiparameter flow cytometry strategy and integrating new clinical and histological criteria of the regression, we show that T cells and B cells are present only in the late stages, arguing against their role in the initial destruction of malignant cells. NK cells infiltrate the tumors before T cells and therefore might be involved in the induction of the regression process. Myeloid cells represent the main immune population within the tumor microenvironment regardless of the regression stage. Among those, MHCII+ CD163- macrophages that differ phenotypically and functionally compared to other tumor-associated macrophages, increase in number together with the first signs of regression suggesting their crucial contribution to initiating the regression process. Our study supports the importance of macrophage reprogramming in humans to improve current immunotherapy for metastatic melanoma.© 2023. The Author(s).