Enriched HLA-E and CD94/NKG2A interaction limits antitumor CD8+ tumor-infiltrating T lymphocyte responses
Immunotherapy treatments with anti-PD-1 boost recovery in less than 30% of treated cancer patients, indicating the complexity of the tumor microenvironment. Expression of HLA-E is linked to poor clinical outcomes in mice and human patients. However, the contributions to immune evasion of HLA-E, a li...
| Päätekijät: | , , , , , , , , , , , , , , , , , |
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| Aineistotyyppi: | Journal article |
| Kieli: | English |
| Julkaistu: |
American Association for Cancer Research
2019
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| _version_ | 1826260959792988160 |
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| author | Abd Hamid, M Wang, R Yao, X Fan, P Li, X Chang, X Feng, Y Jones, S Maldonado-Perez, D Waugh, C Verrill, C Simmons, A Cerundolo, V McMichael, A Conlon, C Wang, X Peng, Y Dong, T |
| author_facet | Abd Hamid, M Wang, R Yao, X Fan, P Li, X Chang, X Feng, Y Jones, S Maldonado-Perez, D Waugh, C Verrill, C Simmons, A Cerundolo, V McMichael, A Conlon, C Wang, X Peng, Y Dong, T |
| author_sort | Abd Hamid, M |
| collection | OXFORD |
| description | Immunotherapy treatments with anti-PD-1 boost recovery in less than 30% of treated cancer patients, indicating the complexity of the tumor microenvironment. Expression of HLA-E is linked to poor clinical outcomes in mice and human patients. However, the contributions to immune evasion of HLA-E, a ligand for the inhibitory CD94/NKG2A receptor, when expressed on tumors, compared with adjacent tissue and peripheral blood mononuclear cells, remains unclear. In this study, we report that epithelial-derived cancer cells, tumor macrophages, and CD141+ conventional dendritic cells (cDC) contributed to HLA-E enrichment in carcinomas. Different cancer types showed a similar pattern of enrichment. Enrichment correlated to NKG2A upregulation on CD8+ tumor-infiltrating T lymphocytes (TIL) but not on CD4+ TILs. CD94/NKG2A is exclusively expressed on PD-1high TILs while lacking intratumoral CD103 expression. We also found that the presence of CD94/NKG2A on human tumor–specific T cells impairs IL2 receptor–dependent proliferation, which affects IFNγ-mediated responses and antitumor cytotoxicity. These functionalities recover following antibody-mediated blockade in vitro and ex vivo. Our results suggest that enriched HLA-E:CD94/NKG2A inhibitory interaction can impair survival of PD-1high TILs in the tumor microenvironment. |
| first_indexed | 2024-03-06T19:14:01Z |
| format | Journal article |
| id | oxford-uuid:17bafd3e-adbd-496f-a087-68a92bc032cd |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:14:01Z |
| publishDate | 2019 |
| publisher | American Association for Cancer Research |
| record_format | dspace |
| spelling | oxford-uuid:17bafd3e-adbd-496f-a087-68a92bc032cd2022-03-26T10:39:11ZEnriched HLA-E and CD94/NKG2A interaction limits antitumor CD8+ tumor-infiltrating T lymphocyte responsesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:17bafd3e-adbd-496f-a087-68a92bc032cdEnglishSymplectic Elements at OxfordAmerican Association for Cancer Research2019Abd Hamid, MWang, RYao, XFan, PLi, XChang, XFeng, YJones, SMaldonado-Perez, DWaugh, CVerrill, CSimmons, ACerundolo, VMcMichael, AConlon, CWang, XPeng, YDong, TImmunotherapy treatments with anti-PD-1 boost recovery in less than 30% of treated cancer patients, indicating the complexity of the tumor microenvironment. Expression of HLA-E is linked to poor clinical outcomes in mice and human patients. However, the contributions to immune evasion of HLA-E, a ligand for the inhibitory CD94/NKG2A receptor, when expressed on tumors, compared with adjacent tissue and peripheral blood mononuclear cells, remains unclear. In this study, we report that epithelial-derived cancer cells, tumor macrophages, and CD141+ conventional dendritic cells (cDC) contributed to HLA-E enrichment in carcinomas. Different cancer types showed a similar pattern of enrichment. Enrichment correlated to NKG2A upregulation on CD8+ tumor-infiltrating T lymphocytes (TIL) but not on CD4+ TILs. CD94/NKG2A is exclusively expressed on PD-1high TILs while lacking intratumoral CD103 expression. We also found that the presence of CD94/NKG2A on human tumor–specific T cells impairs IL2 receptor–dependent proliferation, which affects IFNγ-mediated responses and antitumor cytotoxicity. These functionalities recover following antibody-mediated blockade in vitro and ex vivo. Our results suggest that enriched HLA-E:CD94/NKG2A inhibitory interaction can impair survival of PD-1high TILs in the tumor microenvironment. |
| spellingShingle | Abd Hamid, M Wang, R Yao, X Fan, P Li, X Chang, X Feng, Y Jones, S Maldonado-Perez, D Waugh, C Verrill, C Simmons, A Cerundolo, V McMichael, A Conlon, C Wang, X Peng, Y Dong, T Enriched HLA-E and CD94/NKG2A interaction limits antitumor CD8+ tumor-infiltrating T lymphocyte responses |
| title | Enriched HLA-E and CD94/NKG2A interaction limits antitumor CD8+ tumor-infiltrating T lymphocyte responses |
| title_full | Enriched HLA-E and CD94/NKG2A interaction limits antitumor CD8+ tumor-infiltrating T lymphocyte responses |
| title_fullStr | Enriched HLA-E and CD94/NKG2A interaction limits antitumor CD8+ tumor-infiltrating T lymphocyte responses |
| title_full_unstemmed | Enriched HLA-E and CD94/NKG2A interaction limits antitumor CD8+ tumor-infiltrating T lymphocyte responses |
| title_short | Enriched HLA-E and CD94/NKG2A interaction limits antitumor CD8+ tumor-infiltrating T lymphocyte responses |
| title_sort | enriched hla e and cd94 nkg2a interaction limits antitumor cd8 tumor infiltrating t lymphocyte responses |
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