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MHC-II neoantigens shape tumour immunity and response to immunotherapy
The ability of the immune system to eliminate and shape the immunogenicity of tumours defines the process of cancer immunoediting . Immunotherapies such as those that target immune checkpoint molecules can be used to augment immune-mediated elimination of tumours and have resulted in durable respons...
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Published in: | Nature (London) 2019-10, Vol.574 (7780), p.696-701 |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | The ability of the immune system to eliminate and shape the immunogenicity of tumours defines the process of cancer immunoediting
. Immunotherapies such as those that target immune checkpoint molecules can be used to augment immune-mediated elimination of tumours and have resulted in durable responses in patients with cancer that did not respond to previous treatments. However, only a subset of patients benefit from immunotherapy and more knowledge about what is required for successful treatment is needed
. Although the role of tumour neoantigen-specific CD8
T cells in tumour rejection is well established
, the roles of other subsets of T cells have received less attention. Here we show that spontaneous and immunotherapy-induced anti-tumour responses require the activity of both tumour-antigen-specific CD8
and CD4
T cells, even in tumours that do not express major histocompatibility complex (MHC) class II molecules. In addition, the expression of MHC class II-restricted antigens by tumour cells is required at the site of successful rejection, indicating that activation of CD4
T cells must also occur in the tumour microenvironment. These findings suggest that MHC class II-restricted neoantigens have a key function in the anti-tumour response that is nonoverlapping with that of MHC class I-restricted neoantigens and therefore needs to be considered when identifying patients who will most benefit from immunotherapy. |
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ISSN: | 0028-0836 1476-4687 |
DOI: | 10.1038/s41586-019-1671-8 |