PMID- 36389707 OWN - NLM STAT- MEDLINE DCOM- 20221130 LR - 20221130 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - Immunotherapy for bilateral multiple ground glass opacities: An exploratory study for synchronous multiple primary lung cancer. PG - 1009621 LID - 10.3389/fimmu.2022.1009621 [doi] LID - 1009621 AB - BACKGROUND: Bilateral multiple ground glass opacities (GGOs) are observed in quite a part of patients with early-stage lung adenocarcinoma. For this so-called synchronous multiple primary lung cancer (sMPLC), targeting immune checkpoint is a favorable option in addition to surgical resection. The purpose of this study is to reveal the safety and efficacy of performing immune checkpoint inhibitors (ICIs) on patients with sMPLC and to explore the biomarkers of the efficacy. METHODS: A total of 21 patients with sMPLC were enrolled and all included cases were pathologically confirmed adenocarcinoma after conducting surgical treatment for unilateral GGOs. ICIs of Sintilimab were then used to target programmed death 1 (200mg i.v., Q3W) for up to 10 cycles. Seven patients of them received the other surgery for contralateral GGOs, and multiomics assessments, including neoantigens, somatic mutations, and methylated loci, were further performed to investigate potential biomarkers. RESULTS: Grade 1 or 2 treatment-related adverse events (AEs) occurred in most of the patients (12/21, 57.1%), and one subject withdrawn for grade 3 AEs. For the seven patients underwent twice surgeries, twelve and thirteen GGOs were achieved before and after the use of ICIs separately, and a favorable efficacy was observed among six lesions after immunotherapy (> 50% pathologic tumor regression). Tumor infiltration T-cell and B-cell were further shown to be associated with the biological activity of ICIs. According to mechanism-based multiomics analyses, MUC19- and PCDHB5- mutations were indicated to correlate with a favorable prognosis of sMPLC underwent immunotherapy, and our results suggested that immunogenetic mutation and associated promoter methylation could provide a quantitative explanation for the pathologic response of GGOs. CONCLUSION: Our study provides evidence that the use of ICIs contributed favorable efficacy and safety to patients with sMPLC. Immune infiltration and immunogenic biomarkers are revealed to be implications of performing ICIs on sMPLC. These preliminary findings exhibit the prospects in performing neoadjuvant or adjuvant immunotherapies on patients with sMPLC. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/showproj.aspx?proj=36878, identifier ChiCTR1900022159. CI - Copyright (c) 2022 Xu, Shi, Wang, Li, Yin, Zhang, Zhu, Jiang, Xia, Qiu, Zhang, Huang, Ma, Meng, Zhu, Dong, Wang and Yin. FAU - Xu, Lin AU - Xu L AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. AD - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. FAU - Shi, Meiqi AU - Shi M AD - Department of Oncology, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Wang, Siwei AU - Wang S AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Li, Ming AU - Li M AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Yin, Wenda AU - Yin W AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Zhang, Jingyuan AU - Zhang J AD - Department of Pathology, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Zhu, Jun AU - Zhu J AD - Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Jiang, Feng AU - Jiang F AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Xia, Wenjia AU - Xia W AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Qiu, Ninglei AU - Qiu N AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Zhang, Zhi AU - Zhang Z AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Huang, Jianfeng AU - Huang J AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Ma, Zhifei AU - Ma Z AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Meng, Fanchen AU - Meng F AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Zhu, Hongyu AU - Zhu H AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Dong, Guozhang AU - Dong G AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. FAU - Wang, Jie AU - Wang J AD - Department of Science and technology, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. AD - Biobank of Lung Cancer, Jiangsu Biobank of Clinical Resources, Nanjing, China. FAU - Yin, Rong AU - Yin R AD - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. AD - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. AD - Department of Science and technology, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China. LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221025 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Biomarkers) RN - 0 (Immunologic Factors) SB - IM MH - Humans MH - *Adenocarcinoma of Lung MH - Biomarkers MH - Immunologic Factors/therapeutic use MH - Immunotherapy/methods MH - *Lung Neoplasms/pathology MH - *Neoplasms, Multiple Primary PMC - PMC9642914 OTO - NOTNLM OT - immunogenic biomarkers OT - immunotherapy OT - pathologic response OT - synchronous multiple primary lung cancer OT - therapeutic indicator COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/11/18 06:00 MHDA- 2022/11/22 06:00 PMCR- 2022/01/01 CRDT- 2022/11/17 12:43 PHST- 2022/08/02 00:00 [received] PHST- 2022/10/05 00:00 [accepted] PHST- 2022/11/17 12:43 [entrez] PHST- 2022/11/18 06:00 [pubmed] PHST- 2022/11/22 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.1009621 [doi] PST - epublish SO - Front Immunol. 2022 Oct 25;13:1009621. doi: 10.3389/fimmu.2022.1009621. eCollection 2022.