The Anatomical Location Shapes the Immune Infiltrate in Tumors of Same Etiology and Affects Survival
The Anatomical Location Shapes the Immune Infiltrate in Tumors of Same Etiology and Affects Survival
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DOI：
10.1158/1078-0432.ccr-18-1749
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发表时间：
2019-01-01
影响因子：
11.5
通讯作者：
van der Burg, Sjoerd H.
中科院分区：
文献类型：
--
作者：
Santegoets, Saskia J.;van Ham, Vanessa J.;van der Burg, Sjoerd H.
目的：肿瘤免疫微环境决定临床结果。实验设计：我们应用高维单细胞质量细胞计数法[飞行时间计数法（CytometrybyTime-Of-Flight，CyTOF）]分析和功能研究来分析人乳头瘤病毒（HPV）诱导的宫颈原发性肿瘤中的免疫细胞群。结果：尽管这些肿瘤的病因相同，但它们的淋巴细胞浸润的组成和功能有很大不同。宫颈癌的CD 4：CD 8比值比OPSCC低3倍，并且含有更多活化的CD 8（+）CD 103（+）CD 161（+）效应T细胞和更少的CD 4（+）CD 161（+）效应记忆T细胞。在肿瘤特异性T细胞中，CD 161（+）效应细胞产生的细胞因子水平最高。宫颈癌和OPSCC之间CD 4（+）T细胞浸润的差异反映在肿瘤内HPV特异性CD 4（+）T细胞的检出率及其对OPSCC和宫颈癌生存的影响上。这些患者的外周血单核细胞组成，但是，是相似的。结论：组织的起源显着影响的整体形状的免疫浸润在原发性肿瘤。
Purpose: The tumor immune microenvironment determines clinical outcome. Whether the original tissue in which a primary tumor develops influences this microenvironment is not well understood.Experimental Design: We applied high-dimensional single-cell mass cytometry [Cytometry by Time-Of-Flight (CyTOF)] analysis and functional studies to analyze immune cell populations in human papillomavirus (HPV)-induced primary tumors of the cervix (cervical carcinoma) and oropharynx (oropharyngeal squamous cell carcinoma, OPSCC).Results: Despite the same etiology of these tumors, the composition and functionality of their lymphocytic infiltrate substantially differed. Cervical carcinoma displayed a 3-fold lower CD4:CD8 ratio and contained more activated CD8(+)CD103(+)CD161(+) effector T cells and less CD4(+)CD161(+) effector memory T cells than OPSCC. CD161(+) effector cells produced the highest cytokine levels among tumor-specific T cells. Differences in CD4(+) T-cell infiltration between cervical carcinoma and OPSCC were reflected in the detection rate of intratumoral HPV-specific CD4(+) T cells and in their impact on OPSCC and cervical carcinoma survival. The peripheral blood mononuclear cell composition of these patients, however, was similar.Conclusions: The tissue of origin significantly affects the overall shape of the immune infiltrate in primary tumors.