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黑色素瘤中辅助性和调节性抗肿瘤CD4+T细胞图谱问世
2022-05-05 16:23

美国哈佛医学院Catherine J. Wu、Giacomo Oliveira等研究人员合作绘制出黑色素瘤中辅助性和调节性抗肿瘤CD4+T细胞图谱。相关论文于2022年5月4日在线发表在《自然》杂志上。

研究人员对浸润在人类黑色素瘤标本中的CD4+T细胞的表型和肿瘤特异性进行了深入分析,发现耗竭的细胞毒性CD4+T细胞可以通过识别人类白细胞抗原(HLA)II类限制性新抗原,以及HLA I类限制性肿瘤相关抗原而直接被黑色素瘤细胞诱导。CD4+T调节(TReg)细胞可通过抗原呈递细胞呈递肿瘤抗原而间接诱发。值得注意的是,许多肿瘤反应性CD4+TReg克隆被HLA II类阳性黑色素瘤直接刺激,并显示出对黑色素瘤新抗原的特异性。这种现象是在肿瘤新抗原负荷极高的情况下观察到的,研究人员通过对116个黑色素瘤标本的分析,证实了这与HLA II类阳性有关。
 
这些数据揭示了黑色素瘤中浸润性CD4+T细胞的情况,并指出HLA II类限制性新抗原的呈现和免疫抑制性CD4+TReg细胞的直接参与是HLA II类阳性的黑色素瘤所青睐的一种免疫逃逸机制。
 
据了解,在肿瘤微环境中,CD4+T细胞可以通过识别HLA II类分子呈递的抗原来促进或抑制抗肿瘤反应,但对癌症如何共同利用这些生理过程来实现免疫逃逸仍不完全了解。
 
附:英文原文
 
Title: Landscape of helper and regulatory antitumour CD4+ T cells in melanoma

Author: Oliveira, Giacomo, Stromhaug, Kari, Cieri, Nicoletta, Iorgulescu, J. Bryan, Klaeger, Susan, Wolff, Jacquelyn O., Rachimi, Suzanna, Chea, Vipheaviny, Krause, Kate, Freeman, Samuel S., Zhang, Wandi, Li, Shuqiang, Braun, David A., Neuberg, Donna, Carr, Steven A., Livak, Kenneth J., Frederick, Dennie T., Fritsch, Edward F., Wind-Rotolo, Megan, Hacohen, Nir, Sade-Feldman, Moshe, Yoon, Charles H., Keskin, Derin B., Ott, Patrick A., Rodig, Scott J., Boland, Genevieve M., Wu, Catherine J.

Issue&Volume: 2022-05-04

Abstract: Within the tumour microenvironment, CD4+ T cells can promote or suppress antitumour responses through the recognition of antigens presented by human leukocyte antigen (HLA) class II molecules1,2, but how cancers co-opt these physiologic processes to achieve immune evasion remains incompletely understood. Here we performed in-depth analysis of the phenotype and tumour specificity of CD4+ T cells infiltrating human melanoma specimens, finding that exhausted cytotoxic CD4+ T cells could be directly induced by melanoma cells through recognition of HLA class II-restricted neoantigens, and also HLA class I-restricted tumour-associated antigens. CD4+ T regulatory (TReg) cells could be indirectly elicited through presentation of tumour antigens via antigen-presenting cells. Notably, numerous tumour-reactive CD4+ TReg clones were stimulated directly by HLA class II-positive melanoma and demonstrated specificity for melanoma neoantigens. This phenomenon was observed in the presence of an extremely high tumour neoantigen load, which we confirmed to be associated with HLA class II positivity through the analysis of 116 melanoma specimens. Our data reveal the landscape of infiltrating CD4+ T cells in melanoma and point to the presentation of HLA class II-restricted neoantigens and direct engagement of immunosuppressive CD4+ TReg cells as a mechanism of immune evasion that is favoured in HLA class II-positive melanoma. A survey of the CD4+ T cells in human melanomas indicates that immune evasion is mediated through direct stimulation of neoantigen-specific tumour-reactive regulatory T cells by HLA class II-positive melanoma cells.

DOI: 10.1038/s41586-022-04682-5

Source: https://www.nature.com/articles/s41586-022-04682-5

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

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