{"title":"PD-L1阴性晚期非小细胞肺癌对PD-1/CTLA-4双重阻断敏感的临床意义和分子注释。","authors":"Li Wang, Li Liu, Jing Zhao, Xin Yu, Chunxia Su","doi":"10.2147/ITT.S476040","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy has become the standard treatment for driving gene-negative advanced non-small cell lung cancer (NSCLC). However, compared to PD-L1-positive patients, the efficacy of Anti-PD-(L)1 monotherapy is suboptimal in PD-L1-negative advanced NSCLC. In this study, we aim to analyze the optimal immunotherapy approach for PD-L1-negative NSCLC patients and develop a new nomogram to enhance the clinical predictability of immunotherapy for NSCLC patients.</p><p><strong>Methods: </strong>In this study, we retrieved clinical information and genomic data from cBioPortal for NSCLC patients undergoing immunotherapy. Cox regression analyses were utilized to screen the clinical information and genomic data that related to survival. The prognostic-relate genes function was studied by comprehensive bioinformatics analyses. The Kaplan-Meier plot method was employed for survival analysis.</p><p><strong>Results: </strong>A total of 199 PD-L1-negative NSCLC patients were included in this study. Among them, 165 patients received Anti-PD-(L)1 monotherapy, while 34 patients received Anti-PD-(L)1+Anti-CTLA-4 combination therapy. The Anti-PD-(L)1+Anti-CTLA-4 combination therapy demonstrated significantly higher PFS compared to the Anti-PD-(L)1 monotherapy. The mutation status of KRAS, ANO1, COL14A1, LTBP1. ERBB4 and PCSK5 were found to correlate with PFS. Utilizing the clinicopathological parameters and genomic data of the patients, a novel nomogram was developed to predict the prognosis of Anti-PD-(L)1+Anti-CTLA-4 combination therapy.</p><p><strong>Conclusion: </strong>Our study revealed that KRAS, ANO1, COL14A1, LTBP1. ERBB4 and PCSK5 mutation could serve as predictive biomarkers for patients with Anti-PD-(L)1+Anti-CTLA-4 combination therapy. Our systematic nomogram demonstrates significant potential in predicting the prognosis for NSCLC patients with responsive to dual PD-1/CTLA-4 blockade.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":6.2000,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385699/pdf/","citationCount":"0","resultStr":"{\"title\":\"Clinical Significance and Molecular Annotation for PD-L1 Negative Advanced Non-Small Cell Lung Cancer with Sensitivity to Responsive to Dual PD-1/CTLA-4 Blockade.\",\"authors\":\"Li Wang, Li Liu, Jing Zhao, Xin Yu, Chunxia Su\",\"doi\":\"10.2147/ITT.S476040\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Immunotherapy has become the standard treatment for driving gene-negative advanced non-small cell lung cancer (NSCLC). However, compared to PD-L1-positive patients, the efficacy of Anti-PD-(L)1 monotherapy is suboptimal in PD-L1-negative advanced NSCLC. In this study, we aim to analyze the optimal immunotherapy approach for PD-L1-negative NSCLC patients and develop a new nomogram to enhance the clinical predictability of immunotherapy for NSCLC patients.</p><p><strong>Methods: </strong>In this study, we retrieved clinical information and genomic data from cBioPortal for NSCLC patients undergoing immunotherapy. Cox regression analyses were utilized to screen the clinical information and genomic data that related to survival. The prognostic-relate genes function was studied by comprehensive bioinformatics analyses. The Kaplan-Meier plot method was employed for survival analysis.</p><p><strong>Results: </strong>A total of 199 PD-L1-negative NSCLC patients were included in this study. Among them, 165 patients received Anti-PD-(L)1 monotherapy, while 34 patients received Anti-PD-(L)1+Anti-CTLA-4 combination therapy. The Anti-PD-(L)1+Anti-CTLA-4 combination therapy demonstrated significantly higher PFS compared to the Anti-PD-(L)1 monotherapy. The mutation status of KRAS, ANO1, COL14A1, LTBP1. ERBB4 and PCSK5 were found to correlate with PFS. Utilizing the clinicopathological parameters and genomic data of the patients, a novel nomogram was developed to predict the prognosis of Anti-PD-(L)1+Anti-CTLA-4 combination therapy.</p><p><strong>Conclusion: </strong>Our study revealed that KRAS, ANO1, COL14A1, LTBP1. ERBB4 and PCSK5 mutation could serve as predictive biomarkers for patients with Anti-PD-(L)1+Anti-CTLA-4 combination therapy. Our systematic nomogram demonstrates significant potential in predicting the prognosis for NSCLC patients with responsive to dual PD-1/CTLA-4 blockade.</p>\",\"PeriodicalId\":30986,\"journal\":{\"name\":\"ImmunoTargets and Therapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.2000,\"publicationDate\":\"2024-09-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385699/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ImmunoTargets and Therapy\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2147/ITT.S476040\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ImmunoTargets and Therapy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2147/ITT.S476040","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Clinical Significance and Molecular Annotation for PD-L1 Negative Advanced Non-Small Cell Lung Cancer with Sensitivity to Responsive to Dual PD-1/CTLA-4 Blockade.
Background: Immunotherapy has become the standard treatment for driving gene-negative advanced non-small cell lung cancer (NSCLC). However, compared to PD-L1-positive patients, the efficacy of Anti-PD-(L)1 monotherapy is suboptimal in PD-L1-negative advanced NSCLC. In this study, we aim to analyze the optimal immunotherapy approach for PD-L1-negative NSCLC patients and develop a new nomogram to enhance the clinical predictability of immunotherapy for NSCLC patients.
Methods: In this study, we retrieved clinical information and genomic data from cBioPortal for NSCLC patients undergoing immunotherapy. Cox regression analyses were utilized to screen the clinical information and genomic data that related to survival. The prognostic-relate genes function was studied by comprehensive bioinformatics analyses. The Kaplan-Meier plot method was employed for survival analysis.
Results: A total of 199 PD-L1-negative NSCLC patients were included in this study. Among them, 165 patients received Anti-PD-(L)1 monotherapy, while 34 patients received Anti-PD-(L)1+Anti-CTLA-4 combination therapy. The Anti-PD-(L)1+Anti-CTLA-4 combination therapy demonstrated significantly higher PFS compared to the Anti-PD-(L)1 monotherapy. The mutation status of KRAS, ANO1, COL14A1, LTBP1. ERBB4 and PCSK5 were found to correlate with PFS. Utilizing the clinicopathological parameters and genomic data of the patients, a novel nomogram was developed to predict the prognosis of Anti-PD-(L)1+Anti-CTLA-4 combination therapy.
Conclusion: Our study revealed that KRAS, ANO1, COL14A1, LTBP1. ERBB4 and PCSK5 mutation could serve as predictive biomarkers for patients with Anti-PD-(L)1+Anti-CTLA-4 combination therapy. Our systematic nomogram demonstrates significant potential in predicting the prognosis for NSCLC patients with responsive to dual PD-1/CTLA-4 blockade.
期刊介绍:
Immuno Targets and Therapy is an international, peer-reviewed open access journal focusing on the immunological basis of diseases, potential targets for immune based therapy and treatment protocols employed to improve patient management. Basic immunology and physiology of the immune system in health, and disease will be also covered.In addition, the journal will focus on the impact of management programs and new therapeutic agents and protocols on patient perspectives such as quality of life, adherence and satisfaction.