MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD‐associated NSCLC
Abstract Background Patients with non‐small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) experience worse clinical outcomes but respond better to immunotherapy than patients with NSCLC without COPD. Mucosal‐associated invariant T (MAIT) cells, a versatile population of i...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-03-01
|
| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.7112 |
| _version_ | 1827111580371779584 |
|---|---|
| author | Yanze Yin Ao Zeng Abudumijiti Abuduwayiti Zhilong Xu Keyi Chen Chao Wang Xinyun Fang Jiarui Wang Gening Jiang Jie Dai |
| author_facet | Yanze Yin Ao Zeng Abudumijiti Abuduwayiti Zhilong Xu Keyi Chen Chao Wang Xinyun Fang Jiarui Wang Gening Jiang Jie Dai |
| author_sort | Yanze Yin |
| collection | DOAJ |
| description | Abstract Background Patients with non‐small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) experience worse clinical outcomes but respond better to immunotherapy than patients with NSCLC without COPD. Mucosal‐associated invariant T (MAIT) cells, a versatile population of innate immune T lymphocytes, have a crucial function in the response to infection and tumors. This study investigated the distribution of MAIT cells in COPD‐associated NSCLC and their involvement in the immune response. Methods Flow cytometry, immunohistochemistry, and immunofluorescence were performed on tissue samples of patients with NSCLC, with or without COPD, treated with or without anti‐programmed death 1 (PD1) immunotherapy. MAIT cells were stimulated with 5‐OP‐RU using a mouse subcutaneous tumor model. Results Tumors contained significantly more MAIT cells than paraneoplastic tissues, and CD8+ MAIT cells accounted for more than 90% of these cells. Patients with NSCLC and COPD had higher CD8+ MAIT cell counts than those with NSCLC without COPD. Additionally, patients with NSCLC and COPD displayed reduced expression of the activation marker, CD69, and functional markers, granzyme B (GZMB) and interferon γ (IFNγ), and higher expression of the immune exhaustion marker, PD1. Among patients who received immunotherapy, the proportion with a complete or partial response was higher in those with COPD than in those without COPD. In patients with NSCLC and COPD, the major pathologic response (MPR) group had higher MAIT levels than those in the no major pathologic response (NPR) group. In the mouse subcutaneous tumor model stimulation of MAIT cells using 5‐OP‐RU enhanced the antitumor effects of anti‐PD1. Conclusions In patients with NSCLC and COPD, response to immunotherapy is associated with accumulation of CD8+ MAIT cells showing immune exhaustion. These findings may contribute to innovative approaches for immunotherapy targeting CD8+ MAIT cells. |
| first_indexed | 2024-04-24T18:44:22Z |
| format | Article |
| id | doaj.art-8ec6727171b24c809882a2e678dabb03 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2025-03-20T11:16:27Z |
| publishDate | 2024-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-8ec6727171b24c809882a2e678dabb032024-09-19T05:15:54ZengWileyCancer Medicine2045-76342024-03-01136n/an/a10.1002/cam4.7112MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD‐associated NSCLCYanze Yin0Ao Zeng1Abudumijiti Abuduwayiti2Zhilong Xu3Keyi Chen4Chao Wang5Xinyun Fang6Jiarui Wang7Gening Jiang8Jie Dai9Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai ChinaAbstract Background Patients with non‐small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) experience worse clinical outcomes but respond better to immunotherapy than patients with NSCLC without COPD. Mucosal‐associated invariant T (MAIT) cells, a versatile population of innate immune T lymphocytes, have a crucial function in the response to infection and tumors. This study investigated the distribution of MAIT cells in COPD‐associated NSCLC and their involvement in the immune response. Methods Flow cytometry, immunohistochemistry, and immunofluorescence were performed on tissue samples of patients with NSCLC, with or without COPD, treated with or without anti‐programmed death 1 (PD1) immunotherapy. MAIT cells were stimulated with 5‐OP‐RU using a mouse subcutaneous tumor model. Results Tumors contained significantly more MAIT cells than paraneoplastic tissues, and CD8+ MAIT cells accounted for more than 90% of these cells. Patients with NSCLC and COPD had higher CD8+ MAIT cell counts than those with NSCLC without COPD. Additionally, patients with NSCLC and COPD displayed reduced expression of the activation marker, CD69, and functional markers, granzyme B (GZMB) and interferon γ (IFNγ), and higher expression of the immune exhaustion marker, PD1. Among patients who received immunotherapy, the proportion with a complete or partial response was higher in those with COPD than in those without COPD. In patients with NSCLC and COPD, the major pathologic response (MPR) group had higher MAIT levels than those in the no major pathologic response (NPR) group. In the mouse subcutaneous tumor model stimulation of MAIT cells using 5‐OP‐RU enhanced the antitumor effects of anti‐PD1. Conclusions In patients with NSCLC and COPD, response to immunotherapy is associated with accumulation of CD8+ MAIT cells showing immune exhaustion. These findings may contribute to innovative approaches for immunotherapy targeting CD8+ MAIT cells.https://doi.org/10.1002/cam4.7112chronic obstructive pulmonary diseaseimmune checkpoint inhibitor therapylung cancermucosal‐associated invariant T cellsT cell exhaustion |
| spellingShingle | Yanze Yin Ao Zeng Abudumijiti Abuduwayiti Zhilong Xu Keyi Chen Chao Wang Xinyun Fang Jiarui Wang Gening Jiang Jie Dai MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD‐associated NSCLC Cancer Medicine chronic obstructive pulmonary disease immune checkpoint inhibitor therapy lung cancer mucosal‐associated invariant T cells T cell exhaustion |
| title | MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD‐associated NSCLC |
| title_full | MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD‐associated NSCLC |
| title_fullStr | MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD‐associated NSCLC |
| title_full_unstemmed | MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD‐associated NSCLC |
| title_short | MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD‐associated NSCLC |
| title_sort | mait cells are associated with responsiveness to neoadjuvant immunotherapy in copd associated nsclc |
| topic | chronic obstructive pulmonary disease immune checkpoint inhibitor therapy lung cancer mucosal‐associated invariant T cells T cell exhaustion |
| url | https://doi.org/10.1002/cam4.7112 |
| work_keys_str_mv | AT yanzeyin maitcellsareassociatedwithresponsivenesstoneoadjuvantimmunotherapyincopdassociatednsclc AT aozeng maitcellsareassociatedwithresponsivenesstoneoadjuvantimmunotherapyincopdassociatednsclc AT abudumijitiabuduwayiti maitcellsareassociatedwithresponsivenesstoneoadjuvantimmunotherapyincopdassociatednsclc AT zhilongxu maitcellsareassociatedwithresponsivenesstoneoadjuvantimmunotherapyincopdassociatednsclc AT keyichen maitcellsareassociatedwithresponsivenesstoneoadjuvantimmunotherapyincopdassociatednsclc AT chaowang maitcellsareassociatedwithresponsivenesstoneoadjuvantimmunotherapyincopdassociatednsclc AT xinyunfang maitcellsareassociatedwithresponsivenesstoneoadjuvantimmunotherapyincopdassociatednsclc AT jiaruiwang maitcellsareassociatedwithresponsivenesstoneoadjuvantimmunotherapyincopdassociatednsclc AT geningjiang maitcellsareassociatedwithresponsivenesstoneoadjuvantimmunotherapyincopdassociatednsclc AT jiedai maitcellsareassociatedwithresponsivenesstoneoadjuvantimmunotherapyincopdassociatednsclc |