Tissue immunosurveillance is an important mechanism to prevent cancer. Skin treatment with the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), followed by the tumor promoter 12-O-tetra-decanoyl-phorbol-13-acetate (TPA), is an established murine model for squamous cell carcinoma (SCC). However, the innate immunological events occurring during the initiation of chemical carcinogenesis with DMBA remain elusive. Here, we discovered that natural killer (NK) cells and Langerhans cells (LC) cooperate to impair this oncogenic process in murine skin. The depletion of NK cells or LC caused an accumulation of DNA-damaged, natural killer group 2D-ligand (NKG2D-L) expressing keratinocytes and accelerated tumor growth. Notably, the secretion of TNFα mainly by LC promoted the recruitment of NK cells into the epidermis. Indeed, the TNFα-induced chemokines CCL2 and CXCL10 directed NK cells to DMBA-treated epidermis. Our findings reveal a novel mechanism how innate immune cells cooperate in the inhibition of cutaneous chemical carcinogenesis.

中文翻译：

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朗格汉斯细胞和NK细胞在抑制化学性皮肤癌变中协同作用。

组织免疫监测是预防癌症的重要机制。用致癌物7,12-二甲基苯并（a）蒽（DMBA）继之以肿瘤启动子12-O-四癸酰基-phorbol-13-乙酸盐（TPA）进行皮肤治疗是鳞状细胞癌的成熟鼠模型（ SCC）。但是，在用DMBA引发化学致癌过程中发生的先天免疫事件仍然难以捉摸。在这里，我们发现自然杀伤（NK）细胞和朗格汉斯细胞（LC）协同作用来损害鼠皮中的这种致癌过程。NK细胞或LC的耗竭导致表达角质形成细胞的DNA损伤的自然杀手2D配体（NKG2D-L）积累，并加速了肿瘤的生长。值得注意的是，主要由LC分泌的TNFα促进了NK细胞向表皮的募集。确实，TNFα诱导的趋化因子CCL2和CXCL10将NK细胞导向DMBA处理的表皮。我们的发现揭示了先天免疫细胞如何协同抑制皮肤化学致癌作用的新机制。