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在免疫抑制情况下,皮肤鳞状细胞癌的免疫微环境特征。

Characterisation of the immune microenvironment of cutaneous squamous cell carcinoma in immunosuppression.

机构信息

Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.

Cancer Society Tissue Bank, Christchurch, New Zealand.

出版信息

Exp Dermatol. 2022 Nov;31(11):1720-1728. doi: 10.1111/exd.14650. Epub 2022 Jul 26.

DOI:10.1111/exd.14650
PMID:35861124
Abstract

Cutaneous squamous cell carcinoma (cSCC) is a common cancer. Systemic immunosuppression with drugs such as Prednisone results in more aggressive disease. We hypothesise that more aggressive disease in immunosuppression is the result of immune changes in the tumor microenvironment. We characterised T cell, phagocytic and antigen presenting cell subsets in cSCC and determined if these infiltrates were altered by immunosuppressive therapy. We found a dominant "CD8 profile" in the centre of cSCC lesions, with CD8 cells correlating with Tbet, FoxP3, OX40 and "M2-like" macrophages, whereas a "Tbet and granulocyte profile" with associated inflammation predominated at the margin of the tumor. Individuals on systemic immunosuppressive therapy had lesions that were comparable in size, stage and number of vessels to immune competent individuals; however, the number of CD11c positive cells in the lesion centre was significantly reduced. We conclude that cSCC lesions are immunologically heterogeneous across the lesion and that systemically immunosuppressed individuals have reduced CD11c positive cells in the centre of the lesion. The role and detailed phenotype of CD11c positive cells in cSCC lesions warrant further investigation.

摘要

皮肤鳞状细胞癌 (cSCC) 是一种常见的癌症。药物引起的全身性免疫抑制,如泼尼松,会导致疾病更具侵袭性。我们假设免疫抑制中更具侵袭性的疾病是肿瘤微环境中免疫变化的结果。我们对 cSCC 中的 T 细胞、吞噬细胞和抗原呈递细胞亚群进行了特征描述,并确定这些浸润是否被免疫抑制治疗改变。我们发现 cSCC 病变中心存在占主导地位的“CD8 特征”,CD8 细胞与 Tbet、FoxP3、OX40 和“M2 样”巨噬细胞相关,而“Tbet 和粒细胞特征”与相关炎症则在肿瘤边缘占主导地位。接受全身性免疫抑制治疗的个体的病变在大小、分期和血管数量方面与免疫功能正常的个体相当;然而,病变中心的 CD11c 阳性细胞数量显著减少。我们得出结论,cSCC 病变在整个病变中具有免疫异质性,而接受全身性免疫抑制治疗的个体在病变中心的 CD11c 阳性细胞数量减少。CD11c 阳性细胞在 cSCC 病变中的作用和详细表型值得进一步研究。

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