Expression of tumour-specific antigens underlies cancer immunoediting
Cancer immunoediting is a process by which immune cells, particularly lymphocytes of the adaptive immune system, protect the host from the development of cancer and alter tumour progression by driving the outgrowth of tumour cells with decreased sensitivity to immune attack1, 2. Carcinogen-induced m...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2012
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| Online Access: | http://hdl.handle.net/1721.1/73483 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0001-9076-8475 |
| _version_ | 1811071544166711296 |
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| author | DuPage, Michel J. Mazumdar, Claire Schmidt, Leah Marie Cheung, Ann Jacks, Tyler E. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology DuPage, Michel J. Mazumdar, Claire Schmidt, Leah Marie Cheung, Ann Jacks, Tyler E. |
| author_sort | DuPage, Michel J. |
| collection | MIT |
| description | Cancer immunoediting is a process by which immune cells, particularly lymphocytes of the adaptive immune system, protect the host from the development of cancer and alter tumour progression by driving the outgrowth of tumour cells with decreased sensitivity to immune attack1, 2. Carcinogen-induced mouse models of cancer have shown that primary tumour susceptibility is thereby enhanced in immune-compromised mice, whereas the capacity for such tumours to grow after transplantation into wild-type mice is reduced2, 3. However, many questions about the process of cancer immunoediting remain unanswered, in part because of the known antigenic complexity and heterogeneity of carcinogen-induced tumours4. Here we adapted a genetically engineered, autochthonous mouse model of sarcomagenesis to investigate the process of cancer immunoediting. This system allows us to monitor the onset and growth of immunogenic and non-immunogenic tumours induced in situ that harbour identical genetic and histopathological characteristics. By comparing the development of such tumours in immune-competent mice with their development in mice with broad immunodeficiency or specific antigenic tolerance, we show that recognition of tumour-specific antigens by lymphocytes is critical for immunoediting against sarcomas. Furthermore, primary sarcomas were edited to become less immunogenic through the selective outgrowth of cells that were able to escape T lymphocyte attack. Loss of tumour antigen expression or presentation on major histocompatibility complex I was necessary and sufficient for this immunoediting process to occur. These results highlight the importance of tumour-specific-antigen expression in immune surveillance, and potentially, immunotherapy. |
| first_indexed | 2024-09-23T08:52:51Z |
| format | Article |
| id | mit-1721.1/73483 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:52:51Z |
| publishDate | 2012 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/734832022-01-18T17:58:01Z Expression of tumour-specific antigens underlies cancer immunoediting DuPage, Michel J. Mazumdar, Claire Schmidt, Leah Marie Cheung, Ann Jacks, Tyler E. Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. School of Science Koch Institute for Integrative Cancer Research at MIT DuPage, Michel J. Mazumdar, Claire Schmidt, Leah Marie Cheung, Ann Jacks, Tyler E. Cancer immunoediting is a process by which immune cells, particularly lymphocytes of the adaptive immune system, protect the host from the development of cancer and alter tumour progression by driving the outgrowth of tumour cells with decreased sensitivity to immune attack1, 2. Carcinogen-induced mouse models of cancer have shown that primary tumour susceptibility is thereby enhanced in immune-compromised mice, whereas the capacity for such tumours to grow after transplantation into wild-type mice is reduced2, 3. However, many questions about the process of cancer immunoediting remain unanswered, in part because of the known antigenic complexity and heterogeneity of carcinogen-induced tumours4. Here we adapted a genetically engineered, autochthonous mouse model of sarcomagenesis to investigate the process of cancer immunoediting. This system allows us to monitor the onset and growth of immunogenic and non-immunogenic tumours induced in situ that harbour identical genetic and histopathological characteristics. By comparing the development of such tumours in immune-competent mice with their development in mice with broad immunodeficiency or specific antigenic tolerance, we show that recognition of tumour-specific antigens by lymphocytes is critical for immunoediting against sarcomas. Furthermore, primary sarcomas were edited to become less immunogenic through the selective outgrowth of cells that were able to escape T lymphocyte attack. Loss of tumour antigen expression or presentation on major histocompatibility complex I was necessary and sufficient for this immunoediting process to occur. These results highlight the importance of tumour-specific-antigen expression in immune surveillance, and potentially, immunotherapy. National Institutes of Health (U.S.) (Grant 1 U54 CA126515-01) National Cancer Institute (U.S.) (Cancer Center Support Grant P30-CA14051) Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award JohnD. Proctor Foundation Daniel K. Ludwig Scholar 2012-09-28T17:28:47Z 2012-09-28T17:28:47Z 2012-02 2011-08 Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/73483 DuPage, Michel J. et al. “Expression of Tumour-specific Antigens Underlies Cancer Immunoediting.” Nature 482.7385 (2012): 405–409. https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0001-9076-8475 en_US http://dx.doi.org/10.1038/nature10803 Nature Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group PMC |
| spellingShingle | DuPage, Michel J. Mazumdar, Claire Schmidt, Leah Marie Cheung, Ann Jacks, Tyler E. Expression of tumour-specific antigens underlies cancer immunoediting |
| title | Expression of tumour-specific antigens underlies cancer immunoediting |
| title_full | Expression of tumour-specific antigens underlies cancer immunoediting |
| title_fullStr | Expression of tumour-specific antigens underlies cancer immunoediting |
| title_full_unstemmed | Expression of tumour-specific antigens underlies cancer immunoediting |
| title_short | Expression of tumour-specific antigens underlies cancer immunoediting |
| title_sort | expression of tumour specific antigens underlies cancer immunoediting |
| url | http://hdl.handle.net/1721.1/73483 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0001-9076-8475 |
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