Ping Yang, Shangxiang He, Linyin Fan, Ling Ye, Heng Weng
{"title":"晚期非小细胞肺癌免疫耐药的危险因素及靶向治疗改善预后的优势","authors":"Ping Yang, Shangxiang He, Linyin Fan, Ling Ye, Heng Weng","doi":"10.62347/FGAY1920","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>The advent of immunotherapy has transformed the therapeutic landscape for advanced non-small cell lung cancer (NSCLC); nonetheless, the emergence of resistance to immunotherapy poses a considerable obstacle. Our research sought to identify factors contributing to immunotherapy resistance and to assess the effectiveness of subsequent treatments in patients with advanced NSCLC who have been exposed to immune checkpoint inhibitors (ICIs).</p><p><strong>Methods: </strong>This retrospective study analyzed data from 232 individuals with advanced NSCLC who were treated with ICIs during January 2020 to December 2023. Based on their response to ICIs, these patients were classified into two groups: immunoresistance group (IM group) and non-immunoresistance group (NIM group). Data collected included demographics, clinical parameters, cytokine profiles, tumor mutational burden (TMB), PD-L1 expression, overall survival (OS), progression-free survival (PFS), and adverse events. The association between risk factors and immunoresistance were assessed, and second-line treatment outcomes were evaluated.</p><p><strong>Results: </strong>Key risk factors for immunoresistance included lower TMB, higher levels of interleukin-10 (IL-10), and PD-L1 expression ≥ 50%. TMB was inversely correlated with immunoresistance (rho = -0.838, <i>P</i> < 0.001). In multivariate analysis, IL-10 remained a significant risk factor (OR = 33.654, <i>P</i> = 0.021), whereas TMB was protective (OR = 0.786, <i>P</i> < 0.001). Second-line targeted therapy significantly improved OS (8.72 ± 2.02 months) and PFS (5.37 ± 2.15 months) compared to chemotherapy (OS: 7.93 ± 2.13 months; PFS: 4.86 ± 1.68 months) (<i>P</i> < 0.05). The targeted therapy group experienced distinct side effects, notably increased hypertension and hand-foot syndrome, while chemotherapy group had higher rates of fatigue (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>Immunoresistance in advanced NSCLC is influenced by IL-10, TMB, and PD-L1 expression. Targeted therapies offer superior outcomes than chemotherapy, though side effect management remains crucial.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 2","pages":"573-586"},"PeriodicalIF":3.6000,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897627/pdf/","citationCount":"0","resultStr":"{\"title\":\"Risk factors for immunoresistance in advanced non-small cell lung cancer and the advantages of targeted therapy in improving prognosis.\",\"authors\":\"Ping Yang, Shangxiang He, Linyin Fan, Ling Ye, Heng Weng\",\"doi\":\"10.62347/FGAY1920\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>The advent of immunotherapy has transformed the therapeutic landscape for advanced non-small cell lung cancer (NSCLC); nonetheless, the emergence of resistance to immunotherapy poses a considerable obstacle. Our research sought to identify factors contributing to immunotherapy resistance and to assess the effectiveness of subsequent treatments in patients with advanced NSCLC who have been exposed to immune checkpoint inhibitors (ICIs).</p><p><strong>Methods: </strong>This retrospective study analyzed data from 232 individuals with advanced NSCLC who were treated with ICIs during January 2020 to December 2023. Based on their response to ICIs, these patients were classified into two groups: immunoresistance group (IM group) and non-immunoresistance group (NIM group). Data collected included demographics, clinical parameters, cytokine profiles, tumor mutational burden (TMB), PD-L1 expression, overall survival (OS), progression-free survival (PFS), and adverse events. The association between risk factors and immunoresistance were assessed, and second-line treatment outcomes were evaluated.</p><p><strong>Results: </strong>Key risk factors for immunoresistance included lower TMB, higher levels of interleukin-10 (IL-10), and PD-L1 expression ≥ 50%. TMB was inversely correlated with immunoresistance (rho = -0.838, <i>P</i> < 0.001). In multivariate analysis, IL-10 remained a significant risk factor (OR = 33.654, <i>P</i> = 0.021), whereas TMB was protective (OR = 0.786, <i>P</i> < 0.001). Second-line targeted therapy significantly improved OS (8.72 ± 2.02 months) and PFS (5.37 ± 2.15 months) compared to chemotherapy (OS: 7.93 ± 2.13 months; PFS: 4.86 ± 1.68 months) (<i>P</i> < 0.05). The targeted therapy group experienced distinct side effects, notably increased hypertension and hand-foot syndrome, while chemotherapy group had higher rates of fatigue (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>Immunoresistance in advanced NSCLC is influenced by IL-10, TMB, and PD-L1 expression. Targeted therapies offer superior outcomes than chemotherapy, though side effect management remains crucial.</p>\",\"PeriodicalId\":7437,\"journal\":{\"name\":\"American journal of cancer research\",\"volume\":\"15 2\",\"pages\":\"573-586\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2025-02-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897627/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American journal of cancer research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.62347/FGAY1920\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.62347/FGAY1920","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Risk factors for immunoresistance in advanced non-small cell lung cancer and the advantages of targeted therapy in improving prognosis.
Objectives: The advent of immunotherapy has transformed the therapeutic landscape for advanced non-small cell lung cancer (NSCLC); nonetheless, the emergence of resistance to immunotherapy poses a considerable obstacle. Our research sought to identify factors contributing to immunotherapy resistance and to assess the effectiveness of subsequent treatments in patients with advanced NSCLC who have been exposed to immune checkpoint inhibitors (ICIs).
Methods: This retrospective study analyzed data from 232 individuals with advanced NSCLC who were treated with ICIs during January 2020 to December 2023. Based on their response to ICIs, these patients were classified into two groups: immunoresistance group (IM group) and non-immunoresistance group (NIM group). Data collected included demographics, clinical parameters, cytokine profiles, tumor mutational burden (TMB), PD-L1 expression, overall survival (OS), progression-free survival (PFS), and adverse events. The association between risk factors and immunoresistance were assessed, and second-line treatment outcomes were evaluated.
Results: Key risk factors for immunoresistance included lower TMB, higher levels of interleukin-10 (IL-10), and PD-L1 expression ≥ 50%. TMB was inversely correlated with immunoresistance (rho = -0.838, P < 0.001). In multivariate analysis, IL-10 remained a significant risk factor (OR = 33.654, P = 0.021), whereas TMB was protective (OR = 0.786, P < 0.001). Second-line targeted therapy significantly improved OS (8.72 ± 2.02 months) and PFS (5.37 ± 2.15 months) compared to chemotherapy (OS: 7.93 ± 2.13 months; PFS: 4.86 ± 1.68 months) (P < 0.05). The targeted therapy group experienced distinct side effects, notably increased hypertension and hand-foot syndrome, while chemotherapy group had higher rates of fatigue (P < 0.05).
Conclusion: Immunoresistance in advanced NSCLC is influenced by IL-10, TMB, and PD-L1 expression. Targeted therapies offer superior outcomes than chemotherapy, though side effect management remains crucial.
期刊介绍：
The American Journal of Cancer Research (AJCR) (ISSN 2156-6976), is an independent open access, online only journal to facilitate rapid dissemination of novel discoveries in basic science and treatment of cancer. It was founded by a group of scientists for cancer research and clinical academic oncologists from around the world, who are devoted to the promotion and advancement of our understanding of the cancer and its treatment. The scope of AJCR is intended to encompass that of multi-disciplinary researchers from any scientific discipline where the primary focus of the research is to increase and integrate knowledge about etiology and molecular mechanisms of carcinogenesis with the ultimate aim of advancing the cure and prevention of this increasingly devastating disease. To achieve these aims AJCR will publish review articles, original articles and new techniques in cancer research and therapy. It will also publish hypothesis, case reports and letter to the editor. Unlike most other open access online journals, AJCR will keep most of the traditional features of paper print that we are all familiar with, such as continuous volume, issue numbers, as well as continuous page numbers to retain our comfortable familiarity towards an academic journal.
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