Interleukin (IL)-17A is a key proinflammatory cytokine indicated in multiple pathologies, including skin tumorigenesis. While IL-17A is a signature cytokine of Th17 cells, IL-17A is also produced by other cell types, including type 3 innate lymphoid cells (ILC3s) in the skin, particularly in patients with psoriasis. Interestingly, we detect CD45⁺Lin⁻(CD3⁻CD14⁻CD19⁻CD20⁻) IL-17A⁺ cells in the cutaneous squamous cell carcinomas (cSCCs) by flow cytometry of the cell suspensions prepared from tumor tissues. Consistently, we found CD3⁻IL-17⁺ cells in tumor tissue of skin cSCCs by immunohistochemistry staining of serial sections of SCCs from both immunocompetent and immunocompromised patients (e.g., transplant patients on iatrogenic long-term immunosuppressive therapy). In several immunocompromised patients, the CD3⁻IL-17⁺ cells consist of over 90% of the total IL-17⁺ cells in the tumor tissue. Furthermore, these CD3⁻IL-17⁺ cells are negatively stained for SMA, CD11b, and CD19, suggesting that they are unlikely to be fibroblast, myeloid cells, or B cells. Taken together, we found a population of lineage-negative IL-17A-producing cells present in the cSCCs, which share the “CD45⁺Lin⁻” features with ILCs. This study suggests that IL-17A can be produced by immune cell populations other than T cells in skin SCCs.

中文翻译：

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一种独特的谱系 - 阴性细胞群在皮肤鳞状细胞癌中产生 IL-17A。

白细胞介素 (IL)-17A 是一种关键的促炎细胞因子，可用于多种病理，包括皮肤肿瘤发生。虽然 IL-17A 是 Th17 细胞的标志性细胞因子，但其他细胞类型也会产生 IL-17A，包括皮肤中的 3 型先天淋巴细胞 (ILC3)，尤其是银屑病患者。有趣的是，我们通过对从肿瘤组织制备的细胞悬液进行流式细胞术检测皮肤鳞状细胞癌 (cSCC) 中的CD45 ⁺ Lin ^- (CD3 ^- CD14 ^- CD19 ^- CD20 ^- ) IL-17A ⁺细胞。一致地，我们发现 CD3 ^- IL-17 ⁺通过免疫组化对免疫功能正常和免疫功能低下患者（例如，接受医源性长期免疫抑制治疗的移植患者）的 SCC 连续切片进行免疫组织化学染色，检测皮肤 cSCC 肿瘤组织中的细胞。在一些免疫功能低下的患者中，CD3 ^- IL-17 ⁺细胞占肿瘤组织中总 IL-17 ⁺细胞的90% 以上。此外，这些 CD3 ^- IL-17 ⁺细胞的 SMA、CD11b 和 CD19 呈阴性，表明它们不太可能是成纤维细胞、骨髓细胞或 B 细胞。总之，我们发现 cSCC 中存在一群谱系阴性的 IL-17A 产生细胞，它们共享“CD45 ⁺ Lin ^-”具有 ILC 的功能。这项研究表明 IL-17A 可以由皮肤 SCC 中除 T 细胞之外的免疫细胞群产生。