Landscape of helper and regulatory antitumour CD4+ T cells in melanoma
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 molecules 1 , 2 , but how cancers co-opt these physiologic processes to achieve immune evasion remains incompletely u...
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Published in | Nature (London) Vol. 605; no. 7910; pp. 532 - 538 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
19.05.2022
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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 molecules
1
,
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 (T
Reg
) cells could be indirectly elicited through presentation of tumour antigens via antigen-presenting cells. Notably, numerous tumour-reactive CD4
+
T
Reg
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
+
T
Reg
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0028-0836 1476-4687 |
DOI: | 10.1038/s41586-022-04682-5 |