Enhanced immunotherapy response in lung adenocarcinoma patients with COPD: insights into tumor cells and immune microenvironment characteristics
Abstract Background Lung cancer and chronic obstructive pulmonary disease (COPD) are major global health challenges, and their coexistence in patients presents unique clinical complexities. Interestingly, patients with both lung adenocarcinoma (LUAD) and COPD show reduced responses to conventional c...
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BMC
2025-07-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02332-7 |
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| author | Yuji Huang Boxuan Liang Xuewei Chen Zhiming Li Yanhong Deng Jiaxin Du Yizhou Zhong Xi Lin Junjun Fu Jieyu Xie Xin Zhang Zhenlie Huang |
| author_facet | Yuji Huang Boxuan Liang Xuewei Chen Zhiming Li Yanhong Deng Jiaxin Du Yizhou Zhong Xi Lin Junjun Fu Jieyu Xie Xin Zhang Zhenlie Huang |
| author_sort | Yuji Huang |
| collection | DOAJ |
| description | Abstract Background Lung cancer and chronic obstructive pulmonary disease (COPD) are major global health challenges, and their coexistence in patients presents unique clinical complexities. Interestingly, patients with both lung adenocarcinoma (LUAD) and COPD show reduced responses to conventional chemotherapy and targeted therapies but demonstrate enhanced sensitivity to immunotherapy. Methods We investigated this phenomenon using a cohort of 248 LUAD patients undergoing immunotherapy. Single-cell transcriptomic analysis was performed on 187,123 cells from tumor samples, adjacent normal tissues, and peripheral blood mononuclear cells from six treatment-naïve LUAD patients—three with COPD and three without. To further validate these findings, we conducted multiplex fluorescent immunohistochemical (mfIHC) analysis on 34 additional treatment-naïve LUAD patients and analyzed an independent cohort of 65 LUAD patients undergoing immunotherapy. Results We found that COPD-associated LUAD tumors exhibited distinctive features, including elevated expression of human leukocyte antigen I (HLA-I) on malignant cells and a less aggressive tumor phenotype. The immune microenvironment in these tumors was more active, with increased infiltration of NK cells, effector CD4+ T cells, and effector CD8+ T cells. Additionally, we observed higher numbers of exhausted C-X-C motif chemokine ligand 13+ CD8+ T cells and mature dendritic cells enriched in immunoregulatory molecules expressing immune checkpoint genes. These findings were confirmed in both the mfIHC cohort and the independent immunotherapy cohort, where we observed that COPD-related features correlated with improved responses to immunotherapy. Conclusion Our study reveals that COPD leads to elevated HLA-I expression and a more active immune microenvironment in LUAD tumors, characterized by enhanced cytotoxic immune cell infiltration and a shift towards immunoregulatory profiles. These features correlate with improved immunotherapy responses, highlighting the potential for optimizing treatment strategies in LUAD patients with COPD. |
| format | Article |
| id | doaj-art-694d7f3287644b27a4d2abc5aee962ad |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-694d7f3287644b27a4d2abc5aee962ad2025-08-20T03:37:38ZengBMCCell Communication and Signaling1478-811X2025-07-0123112310.1186/s12964-025-02332-7Enhanced immunotherapy response in lung adenocarcinoma patients with COPD: insights into tumor cells and immune microenvironment characteristicsYuji Huang0Boxuan Liang1Xuewei Chen2Zhiming Li3Yanhong Deng4Jiaxin Du5Yizhou Zhong6Xi Lin7Junjun Fu8Jieyu Xie9Xin Zhang10Zhenlie Huang11Department of Cardiovascular Surgery, Zhujiang Hospital, Southern Medical UniversityNMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical UniversityState Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical UniversityNMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical UniversityNMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical UniversityNMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical UniversityDepartment of Cardiovascular Surgery, Zhujiang Hospital, Southern Medical UniversityNMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical UniversityState Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical UniversityDepartment of Cardiovascular Surgery, Zhujiang Hospital, Southern Medical UniversityAbstract Background Lung cancer and chronic obstructive pulmonary disease (COPD) are major global health challenges, and their coexistence in patients presents unique clinical complexities. Interestingly, patients with both lung adenocarcinoma (LUAD) and COPD show reduced responses to conventional chemotherapy and targeted therapies but demonstrate enhanced sensitivity to immunotherapy. Methods We investigated this phenomenon using a cohort of 248 LUAD patients undergoing immunotherapy. Single-cell transcriptomic analysis was performed on 187,123 cells from tumor samples, adjacent normal tissues, and peripheral blood mononuclear cells from six treatment-naïve LUAD patients—three with COPD and three without. To further validate these findings, we conducted multiplex fluorescent immunohistochemical (mfIHC) analysis on 34 additional treatment-naïve LUAD patients and analyzed an independent cohort of 65 LUAD patients undergoing immunotherapy. Results We found that COPD-associated LUAD tumors exhibited distinctive features, including elevated expression of human leukocyte antigen I (HLA-I) on malignant cells and a less aggressive tumor phenotype. The immune microenvironment in these tumors was more active, with increased infiltration of NK cells, effector CD4+ T cells, and effector CD8+ T cells. Additionally, we observed higher numbers of exhausted C-X-C motif chemokine ligand 13+ CD8+ T cells and mature dendritic cells enriched in immunoregulatory molecules expressing immune checkpoint genes. These findings were confirmed in both the mfIHC cohort and the independent immunotherapy cohort, where we observed that COPD-related features correlated with improved responses to immunotherapy. Conclusion Our study reveals that COPD leads to elevated HLA-I expression and a more active immune microenvironment in LUAD tumors, characterized by enhanced cytotoxic immune cell infiltration and a shift towards immunoregulatory profiles. These features correlate with improved immunotherapy responses, highlighting the potential for optimizing treatment strategies in LUAD patients with COPD.https://doi.org/10.1186/s12964-025-02332-7Lung cancerObstructive lung diseaseMalignant cellsTumor immune microenvironmentHuman leukocyte antigen IC-X-C motif chemokine ligand 13 |
| spellingShingle | Yuji Huang Boxuan Liang Xuewei Chen Zhiming Li Yanhong Deng Jiaxin Du Yizhou Zhong Xi Lin Junjun Fu Jieyu Xie Xin Zhang Zhenlie Huang Enhanced immunotherapy response in lung adenocarcinoma patients with COPD: insights into tumor cells and immune microenvironment characteristics Cell Communication and Signaling Lung cancer Obstructive lung disease Malignant cells Tumor immune microenvironment Human leukocyte antigen I C-X-C motif chemokine ligand 13 |
| title | Enhanced immunotherapy response in lung adenocarcinoma patients with COPD: insights into tumor cells and immune microenvironment characteristics |
| title_full | Enhanced immunotherapy response in lung adenocarcinoma patients with COPD: insights into tumor cells and immune microenvironment characteristics |
| title_fullStr | Enhanced immunotherapy response in lung adenocarcinoma patients with COPD: insights into tumor cells and immune microenvironment characteristics |
| title_full_unstemmed | Enhanced immunotherapy response in lung adenocarcinoma patients with COPD: insights into tumor cells and immune microenvironment characteristics |
| title_short | Enhanced immunotherapy response in lung adenocarcinoma patients with COPD: insights into tumor cells and immune microenvironment characteristics |
| title_sort | enhanced immunotherapy response in lung adenocarcinoma patients with copd insights into tumor cells and immune microenvironment characteristics |
| topic | Lung cancer Obstructive lung disease Malignant cells Tumor immune microenvironment Human leukocyte antigen I C-X-C motif chemokine ligand 13 |
| url | https://doi.org/10.1186/s12964-025-02332-7 |
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