Down-regulated HHLA2 enhances neoadjuvant immunotherapy efficacy in patients with non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD)
Abstract Background Emerging data suggested a favorable outcome in advanced non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD) patients treated by immunotherapy. The objective of this study was to investigate the effectiveness of neoadjuvant immunotherapy among NSCL...
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| Language: | English |
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BMC
2024-03-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-024-12137-5 |
| _version_ | 1797233507008774144 |
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| author | Ao Zeng Yanze Yin Zhilong Xu Abudumijiti Abuduwayiti Fujun Yang Mohammed Saud Shaik Chao Wang Keyi Chen Chao Wang Xinyun Fang Jie Dai |
| author_facet | Ao Zeng Yanze Yin Zhilong Xu Abudumijiti Abuduwayiti Fujun Yang Mohammed Saud Shaik Chao Wang Keyi Chen Chao Wang Xinyun Fang Jie Dai |
| author_sort | Ao Zeng |
| collection | DOAJ |
| description | Abstract Background Emerging data suggested a favorable outcome in advanced non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD) patients treated by immunotherapy. The objective of this study was to investigate the effectiveness of neoadjuvant immunotherapy among NSCLC with COPD versus NSCLC without COPD and explore the potential mechanistic links. Patients and methods Patients with NSCLC receiving neoadjuvant immunotherapy and surgery at Shanghai Pulmonary Hospital between November 2020 and January 2023 were reviewed. The assessment of neoadjuvant immunotherapy’s effectiveness was conducted based on the major pathologic response (MPR). The gene expression profile was investigated by RNA sequencing data. Immune cell proportions were examined using flow cytometry. The association between gene expression, immune cells, and pathologic response was validated by immunohistochemistry and single-cell data. Results A total of 230 NSCLC patients who received neoadjuvant immunotherapy were analyzed, including 60 (26.1%) with COPD. Multivariate logistic regression demonstrated that COPD was a predictor for MPR after neoadjuvant immunotherapy [odds ratio (OR), 2.490; 95% confidence interval (CI), 1.295–4.912; P = 0.007]. NSCLC with COPD showed a down-regulation of HERV–H LTR-associating protein 2 (HHLA2), which was an immune checkpoint molecule, and the HHLA2low group demonstrated the enrichment of CD8+CD103+ tissue-resident memory T cells (TRM) compared to the HHLA2high group (11.9% vs. 4.2%, P = 0.013). Single-cell analysis revealed TRM enrichment in the MPR group. Similarly, NSCLC with COPD exhibited a higher proportion of CD8+CD103+TRM compared to NSCLC without COPD (11.9% vs. 4.6%, P = 0.040). Conclusions The study identified NSCLC with COPD as a favorable lung cancer type for neoadjuvant immunotherapy, offering a new perspective on the multimodality treatment of this patient population. Down-regulated HHLA2 in NSCLC with COPD might improve the MPR rate to neoadjuvant immunotherapy owing to the enrichment of CD8+CD103+TRM. Trial registration Approval for the collection and utilization of clinical samples was granted by the Ethics Committee of Shanghai Pulmonary Hospital (Approval number: K23-228). |
| first_indexed | 2024-04-24T16:17:16Z |
| format | Article |
| id | doaj.art-14bbda9f96f04cbb8986cffbc7022727 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-24T16:17:16Z |
| publishDate | 2024-03-01 |
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| series | BMC Cancer |
| spelling | doaj.art-14bbda9f96f04cbb8986cffbc70227272024-03-31T11:23:13ZengBMCBMC Cancer1471-24072024-03-0124111310.1186/s12885-024-12137-5Down-regulated HHLA2 enhances neoadjuvant immunotherapy efficacy in patients with non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD)Ao Zeng0Yanze Yin1Zhilong Xu2Abudumijiti Abuduwayiti3Fujun Yang4Mohammed Saud Shaik5Chao Wang6Keyi Chen7Chao Wang8Xinyun Fang9Jie Dai10Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversitySchool of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityAbstract Background Emerging data suggested a favorable outcome in advanced non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD) patients treated by immunotherapy. The objective of this study was to investigate the effectiveness of neoadjuvant immunotherapy among NSCLC with COPD versus NSCLC without COPD and explore the potential mechanistic links. Patients and methods Patients with NSCLC receiving neoadjuvant immunotherapy and surgery at Shanghai Pulmonary Hospital between November 2020 and January 2023 were reviewed. The assessment of neoadjuvant immunotherapy’s effectiveness was conducted based on the major pathologic response (MPR). The gene expression profile was investigated by RNA sequencing data. Immune cell proportions were examined using flow cytometry. The association between gene expression, immune cells, and pathologic response was validated by immunohistochemistry and single-cell data. Results A total of 230 NSCLC patients who received neoadjuvant immunotherapy were analyzed, including 60 (26.1%) with COPD. Multivariate logistic regression demonstrated that COPD was a predictor for MPR after neoadjuvant immunotherapy [odds ratio (OR), 2.490; 95% confidence interval (CI), 1.295–4.912; P = 0.007]. NSCLC with COPD showed a down-regulation of HERV–H LTR-associating protein 2 (HHLA2), which was an immune checkpoint molecule, and the HHLA2low group demonstrated the enrichment of CD8+CD103+ tissue-resident memory T cells (TRM) compared to the HHLA2high group (11.9% vs. 4.2%, P = 0.013). Single-cell analysis revealed TRM enrichment in the MPR group. Similarly, NSCLC with COPD exhibited a higher proportion of CD8+CD103+TRM compared to NSCLC without COPD (11.9% vs. 4.6%, P = 0.040). Conclusions The study identified NSCLC with COPD as a favorable lung cancer type for neoadjuvant immunotherapy, offering a new perspective on the multimodality treatment of this patient population. Down-regulated HHLA2 in NSCLC with COPD might improve the MPR rate to neoadjuvant immunotherapy owing to the enrichment of CD8+CD103+TRM. Trial registration Approval for the collection and utilization of clinical samples was granted by the Ethics Committee of Shanghai Pulmonary Hospital (Approval number: K23-228).https://doi.org/10.1186/s12885-024-12137-5Non-small cell lung cancerChronic obstructive pulmonary diseaseNeoadjuvant immunotherapyHERV–H LTR-associating protein 2Tissue-resident memory T cells |
| spellingShingle | Ao Zeng Yanze Yin Zhilong Xu Abudumijiti Abuduwayiti Fujun Yang Mohammed Saud Shaik Chao Wang Keyi Chen Chao Wang Xinyun Fang Jie Dai Down-regulated HHLA2 enhances neoadjuvant immunotherapy efficacy in patients with non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD) BMC Cancer Non-small cell lung cancer Chronic obstructive pulmonary disease Neoadjuvant immunotherapy HERV–H LTR-associating protein 2 Tissue-resident memory T cells |
| title | Down-regulated HHLA2 enhances neoadjuvant immunotherapy efficacy in patients with non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD) |
| title_full | Down-regulated HHLA2 enhances neoadjuvant immunotherapy efficacy in patients with non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD) |
| title_fullStr | Down-regulated HHLA2 enhances neoadjuvant immunotherapy efficacy in patients with non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD) |
| title_full_unstemmed | Down-regulated HHLA2 enhances neoadjuvant immunotherapy efficacy in patients with non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD) |
| title_short | Down-regulated HHLA2 enhances neoadjuvant immunotherapy efficacy in patients with non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD) |
| title_sort | down regulated hhla2 enhances neoadjuvant immunotherapy efficacy in patients with non small cell lung cancer nsclc with chronic obstructive pulmonary disease copd |
| topic | Non-small cell lung cancer Chronic obstructive pulmonary disease Neoadjuvant immunotherapy HERV–H LTR-associating protein 2 Tissue-resident memory T cells |
| url | https://doi.org/10.1186/s12885-024-12137-5 |
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