美国哈佛医学院Shadmehr Demehri团队在研究中取得进展。他们的研究发现共生乳头瘤病毒引发的免疫可以预防皮肤癌。10月30日，《自然》杂志在线发表了这项成果。
研究人员发现，针对共生乳头瘤病毒的T细胞免疫抑制了免疫力完整宿主中的皮肤癌，这种免疫力的丧失（而不是HPV的致癌作用）导致免疫抑制患者患皮肤癌的风险显著增加。为了研究乳头状瘤病毒对致癌物驱动皮肤癌的影响，研究人员在免疫力完整的小鼠中感染了几株鼠标乳头瘤病毒1型（MmuPV1）。这些具有对MmuPV1具有天然免疫力的小鼠可以防止化学物质或紫外线辐射以依赖CD8+T细胞的方式诱导皮肤致癌。
针对25种共生β-HPV的RNA和DNA原位杂交探针显示，与邻近的健康皮肤相比，人皮肤癌的病毒活性和载量显著降低，这表明针对病毒阳性肿瘤细胞的强力免疫选择性。与之一致地，来自β-HPV的E7肽激活了未受影响的人类皮肤的CD8+T细胞。这些研究结果揭示了共生病毒有益的作用，并为阻止皮肤癌发展的免疫疗法奠定了基础。
据介绍，免疫抑制会增加与病毒感染有关的癌症的风险。尤其是，与免疫球蛋白β-乳头瘤病毒（β-HPV）感染有关的皮肤鳞状细胞癌的风险在免疫抑制患者中增加了100倍以上。以前的研究还没有建立HPV在驱动皮肤癌发生的因果角色。
附：英文原文
Title: Immunity to commensal papillomaviruses protects against skin cancer
Author: John D. Strickley, Jonathan L. Messerschmidt, Mary E. Awad, Tiancheng Li, Tatsuya Hasegawa, Dat Thinh Ha, Henry W. Nabeta, Paul A. Bevins, Kenneth H. Ngo, Maryam M. Asgari, Rosalynn M. Nazarian, Victor A. Neel, Alfred Bennett Jenson, Joongho Joh, Shadmehr Demehri
Issue&Volume: 2019-10-30
Abstract: Immunosuppression increases the risk of cancers that are associated with viral infection1. In particular, the risk of squamous cell carcinoma of the skinwhich has been associated with beta human papillomavirus (-HPV) infectionis increased by more than 100-fold in immunosuppressed patients24. Previous studies have not established a causative role for HPVs in driving the development of skin cancer. Here we show that T cell immunity against commensal papillomaviruses suppresses skin cancer in immunocompetent hosts, and the loss of this immunityrather than the oncogenic effect of HPVscauses the markedly increased risk of skin cancer in immunosuppressed patients. To investigate the effects of papillomavirus on carcinogen-driven skin cancer, we colonized several strains of immunocompetent mice with mouse papillomavirus type 1 (MmuPV1)5. Mice with natural immunity against MmuPV1 after colonization and acquired immunity through the transfer of T cells from immune mice or by MmuPV1 vaccination were protected against skin carcinogenesis induced by chemicals or by ultraviolet radiation in a manner dependent on CD8+ T cells. RNA and DNA in situ hybridization probes for 25 commensal -HPVs revealed a significant reduction in viral activity and load in human skin cancer compared with the adjacent healthy skin, suggesting a strong immune selection against virus-positive malignant cells. Consistently, E7 peptides from -HPVs activated CD8+ T cells from unaffected human skin. Our findings reveal a beneficial role for commensal viruses and establish a foundation for immune-based approaches that could block the development of skin cancer by boosting immunity against the commensal HPVs present in all of our skin. A mouse model of papillomavirus infection reveals that skin colonization with commensal papillomaviruses protects the immunocompetent host against chemical- and UV-induced skin cancer through CD8+ T cell immunity.
DOI: 10.1038/s41586-019-1719-9
Source:https://www.nature.com/articles/s41586-019-1719-9
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
