Tumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patient
Abstract Immunotherapies targeting PD-1/PD-L1 are now widely used in the clinic to treat a variety of malignancies. While most of the research on T cell exhaustion and PD-1 blockade has been focused on conventional αβ T cells, the contribution of innate-like T cells such as γδ T cells to anti-PD-1/P...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45449-y |
| _version_ | 1797274000675569664 |
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| author | Scott C. Lien Dalam Ly S. Y. Cindy Yang Ben X. Wang Derek L. Clouthier Michael St. Paul Ramy Gadalla Babak Noamani Carlos R. Garcia-Batres Sarah Boross-Harmer Philippe L. Bedard Trevor J. Pugh Anna Spreafico Naoto Hirano Albiruni R. A. Razak Pamela S. Ohashi |
| author_facet | Scott C. Lien Dalam Ly S. Y. Cindy Yang Ben X. Wang Derek L. Clouthier Michael St. Paul Ramy Gadalla Babak Noamani Carlos R. Garcia-Batres Sarah Boross-Harmer Philippe L. Bedard Trevor J. Pugh Anna Spreafico Naoto Hirano Albiruni R. A. Razak Pamela S. Ohashi |
| author_sort | Scott C. Lien |
| collection | DOAJ |
| description | Abstract Immunotherapies targeting PD-1/PD-L1 are now widely used in the clinic to treat a variety of malignancies. While most of the research on T cell exhaustion and PD-1 blockade has been focused on conventional αβ T cells, the contribution of innate-like T cells such as γδ T cells to anti-PD-1/PD-L1 mediated therapy is limited. Here we show that tumor reactive γδ T cells respond to PD-1 blockade in a Merkel cell carcinoma (MCC) patient experiencing a complete response to therapy. We find clonally expanded γδ T cells in the blood and tumor after pembrolizumab treatment, and this Vγ2Vδ1 clonotype recognizes Merkel cancer cells in a TCR-dependent manner. Notably, the intra-tumoral γδ T cells in the MCC patient are characterized by higher expression of PD-1 and TIGIT, relative to conventional CD4 and CD8 T cells. Our results demonstrate that innate-like T cells could also contribute to an anti-tumor response after PD-1 blockade. |
| first_indexed | 2024-03-07T14:52:08Z |
| format | Article |
| id | doaj.art-fd59752fa86742a8a6eab34aa0b37b3b |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:52:08Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-fd59752fa86742a8a6eab34aa0b37b3b2024-03-05T19:41:13ZengNature PortfolioNature Communications2041-17232024-02-0115111110.1038/s41467-024-45449-yTumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patientScott C. Lien0Dalam Ly1S. Y. Cindy Yang2Ben X. Wang3Derek L. Clouthier4Michael St. Paul5Ramy Gadalla6Babak Noamani7Carlos R. Garcia-Batres8Sarah Boross-Harmer9Philippe L. Bedard10Trevor J. Pugh11Anna Spreafico12Naoto Hirano13Albiruni R. A. Razak14Pamela S. Ohashi15Princess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkDivision of Medical Oncology and Haematology, Princess Margaret Cancer Centre, University Health Network, University of TorontoDivision of Medical Oncology and Haematology, Princess Margaret Cancer Centre, University Health Network, University of TorontoPrincess Margaret Cancer Centre, University Health NetworkDivision of Medical Oncology and Haematology, Princess Margaret Cancer Centre, University Health Network, University of TorontoPrincess Margaret Cancer Centre, University Health NetworkDivision of Medical Oncology and Haematology, Princess Margaret Cancer Centre, University Health Network, University of TorontoPrincess Margaret Cancer Centre, University Health NetworkAbstract Immunotherapies targeting PD-1/PD-L1 are now widely used in the clinic to treat a variety of malignancies. While most of the research on T cell exhaustion and PD-1 blockade has been focused on conventional αβ T cells, the contribution of innate-like T cells such as γδ T cells to anti-PD-1/PD-L1 mediated therapy is limited. Here we show that tumor reactive γδ T cells respond to PD-1 blockade in a Merkel cell carcinoma (MCC) patient experiencing a complete response to therapy. We find clonally expanded γδ T cells in the blood and tumor after pembrolizumab treatment, and this Vγ2Vδ1 clonotype recognizes Merkel cancer cells in a TCR-dependent manner. Notably, the intra-tumoral γδ T cells in the MCC patient are characterized by higher expression of PD-1 and TIGIT, relative to conventional CD4 and CD8 T cells. Our results demonstrate that innate-like T cells could also contribute to an anti-tumor response after PD-1 blockade.https://doi.org/10.1038/s41467-024-45449-y |
| spellingShingle | Scott C. Lien Dalam Ly S. Y. Cindy Yang Ben X. Wang Derek L. Clouthier Michael St. Paul Ramy Gadalla Babak Noamani Carlos R. Garcia-Batres Sarah Boross-Harmer Philippe L. Bedard Trevor J. Pugh Anna Spreafico Naoto Hirano Albiruni R. A. Razak Pamela S. Ohashi Tumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patient Nature Communications |
| title | Tumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patient |
| title_full | Tumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patient |
| title_fullStr | Tumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patient |
| title_full_unstemmed | Tumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patient |
| title_short | Tumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patient |
| title_sort | tumor reactive γδ t cells contribute to a complete response to pd 1 blockade in a merkel cell carcinoma patient |
| url | https://doi.org/10.1038/s41467-024-45449-y |
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