Germline Human Leukocyte Antigen Status is Associated With Immunotherapy-Induced Pneumonitis and Treatment Response in Patients With Non–Small Cell Lung Cancer With High Programmed Death-Ligand 1 Expression
Introduction: The germline human leukocyte antigen (HLA) status has been found to be associated with immunotherapy outcomes in patients with NSCLC, but its correlation to immunotherapy-induced pneumonitis and prognostic impact in the Asian population remains largely unknown. Methods: We evaluated th...
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Elsevier
2025-01-01
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| Series: | JTO Clinical and Research Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364324001243 |
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| author | Alvin H.K. Cheung, MBBS, PhD Zeta Mui, MPhil Walter W. Yeung, PhD Chit Chow, PhD Mandy F. Yu, BSc Olivia H. Chen, MD, PhD Kit-Yee Wong, MPhil Fuda Xie, MPhil Yat Ming Lau, MBBS Alfred S-L. Cheng, PhD Wei Kang, PhD Ka-Fai To, MBChB Tony S. Mok, MD Molly S.C. Li, MBBS |
| author_facet | Alvin H.K. Cheung, MBBS, PhD Zeta Mui, MPhil Walter W. Yeung, PhD Chit Chow, PhD Mandy F. Yu, BSc Olivia H. Chen, MD, PhD Kit-Yee Wong, MPhil Fuda Xie, MPhil Yat Ming Lau, MBBS Alfred S-L. Cheng, PhD Wei Kang, PhD Ka-Fai To, MBChB Tony S. Mok, MD Molly S.C. Li, MBBS |
| author_sort | Alvin H.K. Cheung, MBBS, PhD |
| collection | DOAJ |
| description | Introduction: The germline human leukocyte antigen (HLA) status has been found to be associated with immunotherapy outcomes in patients with NSCLC, but its correlation to immunotherapy-induced pneumonitis and prognostic impact in the Asian population remains largely unknown. Methods: We evaluated the HLA genotype of the germline and available tumor samples in 42 patients with programmed death-ligand 1 expression of 50% or higher undergoing pembrolizumab immunotherapy. The HLA allele expression was correlated with tumor response, disease survival, and the occurrence of pneumonitis. Results: It was observed that the germline HLA-C homozygosity and HLA-DRB1∗13 expression were related to a worse progression-free survival and treatment response. Importantly, all patients (7/7 patients) who developed pneumonitis in our cohort expressed the HLA-DPB1∗02 allele, and the incidence of pneumonitis was 31.8% (7/22 patients) in patients expressing this allele compared with 0% (0/20 patients) in those without this allele (p = 0.009). Investigation of the tumor samples from 15 patients revealed some degree of HLA loss in the HLA class I loci in 40% (6/15) of patients, and no significant difference in tumor mutation burden was found among patients with different treatment responses. Conclusion: Taken together, this study evaluated the impact of HLA status in both germline and tumor samples in patients with NSCLC with high programmed death-ligand 1 expression, and the high incidence of immunotherapy-induced pneumonitis in patients expressing the HLA-DPB1∗02 allele may suggest a routine HLA typing and closer monitoring in this patient subset. |
| format | Article |
| id | doaj-art-059884a272f345c18d1c55e8ba3a0eda |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| series | JTO Clinical and Research Reports |
| spelling | doaj-art-059884a272f345c18d1c55e8ba3a0eda2025-01-20T04:17:53ZengElsevierJTO Clinical and Research Reports2666-36432025-01-0161100754Germline Human Leukocyte Antigen Status is Associated With Immunotherapy-Induced Pneumonitis and Treatment Response in Patients With Non–Small Cell Lung Cancer With High Programmed Death-Ligand 1 ExpressionAlvin H.K. Cheung, MBBS, PhD0Zeta Mui, MPhil1Walter W. Yeung, PhD2Chit Chow, PhD3Mandy F. Yu, BSc4Olivia H. Chen, MD, PhD5Kit-Yee Wong, MPhil6Fuda Xie, MPhil7Yat Ming Lau, MBBS8Alfred S-L. Cheng, PhD9Wei Kang, PhD10Ka-Fai To, MBChB11Tony S. Mok, MD12Molly S.C. Li, MBBS13Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, People's Republic of China; State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, People's Republic of ChinaDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, People's Republic of ChinaDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, People's Republic of ChinaDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, People's Republic of China; State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, People's Republic of ChinaDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, People's Republic of ChinaDepartment of Clinical Oncology, Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong, People's Republic of ChinaDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, People's Republic of ChinaDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, People's Republic of ChinaDepartment of Clinical Oncology, Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong, People's Republic of ChinaSchool of Biomedical Sciences, the Chinese University of Hong Kong, Hong Kong, People's Republic of ChinaDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, People's Republic of ChinaDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, People's Republic of China; State Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, People's Republic of ChinaState Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, People's Republic of China; Department of Clinical Oncology, Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong, People's Republic of ChinaState Key Laboratory of Translational Oncology, the Chinese University of Hong Kong, Hong Kong, People's Republic of China; Department of Clinical Oncology, Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong, People's Republic of China; Corresponding author. Address for correspondence: Molly S.C. Li, MBBS, Department of Clinical Oncology, Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong, People's Republic of China.Introduction: The germline human leukocyte antigen (HLA) status has been found to be associated with immunotherapy outcomes in patients with NSCLC, but its correlation to immunotherapy-induced pneumonitis and prognostic impact in the Asian population remains largely unknown. Methods: We evaluated the HLA genotype of the germline and available tumor samples in 42 patients with programmed death-ligand 1 expression of 50% or higher undergoing pembrolizumab immunotherapy. The HLA allele expression was correlated with tumor response, disease survival, and the occurrence of pneumonitis. Results: It was observed that the germline HLA-C homozygosity and HLA-DRB1∗13 expression were related to a worse progression-free survival and treatment response. Importantly, all patients (7/7 patients) who developed pneumonitis in our cohort expressed the HLA-DPB1∗02 allele, and the incidence of pneumonitis was 31.8% (7/22 patients) in patients expressing this allele compared with 0% (0/20 patients) in those without this allele (p = 0.009). Investigation of the tumor samples from 15 patients revealed some degree of HLA loss in the HLA class I loci in 40% (6/15) of patients, and no significant difference in tumor mutation burden was found among patients with different treatment responses. Conclusion: Taken together, this study evaluated the impact of HLA status in both germline and tumor samples in patients with NSCLC with high programmed death-ligand 1 expression, and the high incidence of immunotherapy-induced pneumonitis in patients expressing the HLA-DPB1∗02 allele may suggest a routine HLA typing and closer monitoring in this patient subset.http://www.sciencedirect.com/science/article/pii/S2666364324001243HLAImmunotherapyPD-L1Pneumonitis |
| spellingShingle | Alvin H.K. Cheung, MBBS, PhD Zeta Mui, MPhil Walter W. Yeung, PhD Chit Chow, PhD Mandy F. Yu, BSc Olivia H. Chen, MD, PhD Kit-Yee Wong, MPhil Fuda Xie, MPhil Yat Ming Lau, MBBS Alfred S-L. Cheng, PhD Wei Kang, PhD Ka-Fai To, MBChB Tony S. Mok, MD Molly S.C. Li, MBBS Germline Human Leukocyte Antigen Status is Associated With Immunotherapy-Induced Pneumonitis and Treatment Response in Patients With Non–Small Cell Lung Cancer With High Programmed Death-Ligand 1 Expression JTO Clinical and Research Reports HLA Immunotherapy PD-L1 Pneumonitis |
| title | Germline Human Leukocyte Antigen Status is Associated With Immunotherapy-Induced Pneumonitis and Treatment Response in Patients With Non–Small Cell Lung Cancer With High Programmed Death-Ligand 1 Expression |
| title_full | Germline Human Leukocyte Antigen Status is Associated With Immunotherapy-Induced Pneumonitis and Treatment Response in Patients With Non–Small Cell Lung Cancer With High Programmed Death-Ligand 1 Expression |
| title_fullStr | Germline Human Leukocyte Antigen Status is Associated With Immunotherapy-Induced Pneumonitis and Treatment Response in Patients With Non–Small Cell Lung Cancer With High Programmed Death-Ligand 1 Expression |
| title_full_unstemmed | Germline Human Leukocyte Antigen Status is Associated With Immunotherapy-Induced Pneumonitis and Treatment Response in Patients With Non–Small Cell Lung Cancer With High Programmed Death-Ligand 1 Expression |
| title_short | Germline Human Leukocyte Antigen Status is Associated With Immunotherapy-Induced Pneumonitis and Treatment Response in Patients With Non–Small Cell Lung Cancer With High Programmed Death-Ligand 1 Expression |
| title_sort | germline human leukocyte antigen status is associated with immunotherapy induced pneumonitis and treatment response in patients with non small cell lung cancer with high programmed death ligand 1 expression |
| topic | HLA Immunotherapy PD-L1 Pneumonitis |
| url | http://www.sciencedirect.com/science/article/pii/S2666364324001243 |
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