Cancer Immunology, Immunotherapy最新文献

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Nicotine promotes M2 macrophage polarization through α5-nAChR/SOX2/CSF-1 axis in lung adenocarcinoma. 尼古丁通过α5-nAChR/SOX2/CSF-1轴促进肺腺癌M2巨噬细胞极化
IF 4.6 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2024-11-02 DOI: 10.1007/s00262-024-03866-4
Guiyu Kang, Hui Song, Lei Bo, Qi Liu, Qiang Li, Jingtan Li, Pan Pan, Jingting Wang, Yanfei Jia, Haiji Sun, Xiaoli Ma
{"title":"Nicotine promotes M2 macrophage polarization through α5-nAChR/SOX2/CSF-1 axis in lung adenocarcinoma.","authors":"Guiyu Kang, Hui Song, Lei Bo, Qi Liu, Qiang Li, Jingtan Li, Pan Pan, Jingting Wang, Yanfei Jia, Haiji Sun, Xiaoli Ma","doi":"10.1007/s00262-024-03866-4","DOIUrl":"10.1007/s00262-024-03866-4","url":null,"abstract":"<p><p>α5-nicotinic acetylcholine receptor (α5-nAChR) plays a vital part in lung adenocarcinoma (LUAD). However, it is not comprehensively understood that how the α5-nAChR affects LUAD. Through diverse bioinformatics analyses and immunohistochemistry, the expressions of α5-nAChR and SOX2 as well as their relations were dissected. α5-nAChR regulated the differentiation of monocytes into M2 macrophages by targeting the STAT3/SOX2/CSF-1 signaling in the coculture system by western blotting and ChIP. α5-nAChR-mediated macrophage-mediated LUAD cell migration via SOX2/CSF-1 signaling in the cocultured medium. Correlations of α5-nAChR, SOX2 and M2 phenotype tumor-associated macrophages (TAMs) were validated in mouse LUAD models and clinical samples. α5-nAChR expression was connected to SOX2 expression, smoking and bad prognosis of LUAD among clinical samples. Nicotine-induced SOX2 expression was mediated by α5-nAChR via STAT3. Additionally, SOX2-mediated macrophage colony-stimulating factor (CSF-1) expression contributed to LUAD progression in vitro. Furthermore, α5-nAChR expression was strongly linked to pSTAT3, SOX2 and M2 macrophage marker CD206 expression and negatively correlated with M1 macrophage marker CD86 expression in vivo. It is indicated that M2 macrophages are mediated by the new α5-nAChR /SOX2/CSF-1 axis in nicotine-related LUAD, which is a potential therapeutic strategy for cancer.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 1","pages":"11"},"PeriodicalIF":4.6,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
New insights into the immunomodulatory potential of sialic acid on monocyte-derived dendritic cells. 关于单核细胞衍生树突状细胞上的唾液酸免疫调节潜力的新见解。
IF 4.6 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2024-11-02 DOI: 10.1007/s00262-024-03863-7
Zélia Silva, João Amorim Rabaça, Vanessa Luz, Rita Adubeiro Lourenço, Mariolina Salio, Alexandra Couto Oliveira, Pedro Bule, Sebastian Springer, Paula Alexandra Videira
{"title":"New insights into the immunomodulatory potential of sialic acid on monocyte-derived dendritic cells.","authors":"Zélia Silva, João Amorim Rabaça, Vanessa Luz, Rita Adubeiro Lourenço, Mariolina Salio, Alexandra Couto Oliveira, Pedro Bule, Sebastian Springer, Paula Alexandra Videira","doi":"10.1007/s00262-024-03863-7","DOIUrl":"10.1007/s00262-024-03863-7","url":null,"abstract":"<p><p>Sialic acids at the cell surface of dendritic cells (DCs) play an important immunomodulatory role, and their manipulation enhances DC maturation, leading to heightened T cell activation. Particularly, at the molecular level, the increased stability of surface MHC-I molecules in monocyte-derived DCs (MoDCs) underpins an improved DC: T cell interaction. In this study, we focused on the impact of sialic acid remodelling by treatment with Clostridium perfringens sialidase on MoDCs' phenotypic and functional characteristics. Our investigation juxtaposes this novel approach with the conventional cytokine-based maturation regimen commonly employed in clinical settings.Notably, C. perfringens sialidase remarkably increased MHC-I levels compared to other sialidases having different specificities, supporting the idea that higher MHC-I is due to the cleavage of specific sialoglycans on cell surface proteins. Sialidase treatment induced rapid elevated surface expression of MHC-I, MHC-II and CD40 within an hour, a response not fully replicated by 48 h cytokine cocktail treatment. These increases were also observable 48 h post sialidase treatment. While CD86 and PD-L1 showed significant increases after 48 h of cytokine maturation, 48 h post sialidase treatment showed a higher increase in CD86 and shorter increase in PD-L1. CCR-7 expression was significantly increased 48 h after sialidase treatment but not significantly affected by cytokine maturation. Both treatments promoted higher secretion of the IL-12 cytokine. However, the cytokine cocktail induced a more pronounced IL-12 production. SNA lectin staining analysis demonstrated that the sialic acid profile is significantly altered by sialidase treatment, but not by the cytokine cocktail, which causes only slight sialic acid upregulation. Notably, the lipid-presenting molecules CD1a, CD1b and CD1c remained unaffected by sialidase treatment in MoDCs, a finding also further supported by experiments performed on C1R cells. Inhibition of endogenous sialidases Neu1 and Neu3 during MoDC differentiation did not affect surface MHC-I expression and cytokine secretion. Yet, sialidase activity in MoDCs was minimal, suggesting that sialidase inhibition does not significantly alter MHC-I-related functions. Our study highlights the unique maturation profile induced by sialic acid manipulation in MoDCs. These findings provide insights into the potential of sialic acid manipulation as a rapid immunomodulatory strategy, offering promising avenues for targeted interventions in inflammatory contexts.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 1","pages":"9"},"PeriodicalIF":4.6,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phenotypic insights into genetic risk factors for immune-related adverse events in cancer immunotherapy. 癌症免疫疗法中免疫相关不良事件遗传风险因素的表型研究。
IF 4.6 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2024-11-02 DOI: 10.1007/s00262-024-03854-8
Haochuan Ma, Dili Song, Haibo Zhang, Taidong Li, Xing Jin
{"title":"Phenotypic insights into genetic risk factors for immune-related adverse events in cancer immunotherapy.","authors":"Haochuan Ma, Dili Song, Haibo Zhang, Taidong Li, Xing Jin","doi":"10.1007/s00262-024-03854-8","DOIUrl":"10.1007/s00262-024-03854-8","url":null,"abstract":"<p><strong>Background: </strong>Immune-related adverse events (irAEs) pose substantial challenges in the realm of cancer immunotherapy, frequently affecting treatment efficacy and patient safety. To address the urgent need for identifying risk factors associated with irAEs, we conducted a comprehensive phenotype-wide Mendelian randomization analysis (MR-PheWAS).</p><p><strong>Methods: </strong>Utilizing publicly accessible genome-wide association study (GWAS) data, this investigation evaluated the impact of over 5000 exposure variables on susceptibility to irAEs using univariate Mendelian randomization (MR). We categorized these correlations and further explored potential mechanisms by which associated traits might influence irAEs through multivariate MR.</p><p><strong>Results: </strong>MR-PheWAS identified numerous risk factors for irAEs, encompassing both previously documented and novel associations. Specifically, we identified 105 traits with probable causal relationships to all-grade irAEs and 119 traits with suggestive associations. For high-grade irAEs, we categorized 122 traits as probably associated and 141 as suggestively associated. Notably, multivariate MR analyses uncovered intricate interactions, particularly highlighting how diabetes impacts all-grade irAEs through mediators such as body mass index and sex hormone-binding globulin.</p><p><strong>Conclusions: </strong>This study has not only identified new risk factors for irAEs but also confirmed several well-established ones. Further investigation is crucial to validate and assess these identified risk factors within clinical trials. A mechanistic understanding of these causal factors is essential for improving the management and prevention of irAEs.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 1","pages":"1"},"PeriodicalIF":4.6,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Three-dimensional dynamics of mesothelin-targeted CAR.CIK lymphocytes against ovarian cancer peritoneal carcinomatosis. 间皮素靶向 CAR.CIK 淋巴细胞防治卵巢癌腹膜癌变的三维动态研究。
IF 4.6 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2024-11-02 DOI: 10.1007/s00262-024-03860-w
Federica Galvagno, Valeria Leuci, Annamaria Massa, Chiara Donini, Ramona Rotolo, Sonia Capellero, Alessia Proment, Letizia Vitali, Andrea Maria Lombardi, Valentina Tuninetti, Lorenzo D'Ambrosio, Alessandra Merlini, Elisa Vigna, Giorgio Valabrega, Luca Primo, Alberto Puliafito, Dario Sangiolo
{"title":"Three-dimensional dynamics of mesothelin-targeted CAR.CIK lymphocytes against ovarian cancer peritoneal carcinomatosis.","authors":"Federica Galvagno, Valeria Leuci, Annamaria Massa, Chiara Donini, Ramona Rotolo, Sonia Capellero, Alessia Proment, Letizia Vitali, Andrea Maria Lombardi, Valentina Tuninetti, Lorenzo D'Ambrosio, Alessandra Merlini, Elisa Vigna, Giorgio Valabrega, Luca Primo, Alberto Puliafito, Dario Sangiolo","doi":"10.1007/s00262-024-03860-w","DOIUrl":"10.1007/s00262-024-03860-w","url":null,"abstract":"<p><p>Intraperitoneal cellular immunotherapy with CAR-redirected lymphocytes is an intriguing approach to target peritoneal carcinomatosis (PC) from ovarian cancer (OC), which is currently evaluated in clinical trials. PC displays a composite structure with floating tumor cells within ascites and solid-like masses invading the peritoneum. Therefore, a comprehensive experimental model is crucial to optimize CAR-cell therapies in such a peculiar environment. Here, we explored the activity of cytokine-induced killer lymphocytes (CIK), redirected by CAR against mesothelin (MSLN-CAR.CIK), within reductionistic 3D models resembling the structural complexity of both liquid and solid components of PC. MSLN-CAR.CIK effectively killed and were functionally efficient against OC targets. In a \"floating-like\" 3D context with floating OC spheroids, both tumor localization and killing by MSLN-CAR.CIK were significantly boosted by fluid flow. In a \"solid-like\" context, MSLN-CAR.CIK were recruited through the extracellular matrix on embedded tumor aggregates, with variable kinetics depending on the effector-target distance. Furthermore, MSLN-CAR.CIK penetrated the inner levels of OC spheroids exerting effective tumor killing. Our findings provide currently unknown therapeutically relevant information on intraperitoneal approaches with CAR.CIK, supporting further developments and improvements for clinical studies in the context of locoregional cell therapy approaches for patients with PC from OC.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 1","pages":"6"},"PeriodicalIF":4.6,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ly6E on tumor cells impairs anti-tumor T-cell responses: a novel mechanism of tumor-induced immune exclusion. 肿瘤细胞上的 Ly6E 会损害抗肿瘤 T 细胞反应:肿瘤诱导免疫排斥的新机制。
IF 4.6 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2024-11-02 DOI: 10.1007/s00262-024-03851-x
Lan Hailin, Chen Yiting, Wu Yue, Li Lijun, Zhang Renlu, Chen Yunhan, Zhu Yanyang, Zhang Qiuyu
{"title":"Ly6E on tumor cells impairs anti-tumor T-cell responses: a novel mechanism of tumor-induced immune exclusion.","authors":"Lan Hailin, Chen Yiting, Wu Yue, Li Lijun, Zhang Renlu, Chen Yunhan, Zhu Yanyang, Zhang Qiuyu","doi":"10.1007/s00262-024-03851-x","DOIUrl":"10.1007/s00262-024-03851-x","url":null,"abstract":"<p><strong>Background: </strong>Lymphocyte antigen 6 complex, locus E (Ly6E) has been initially demonstrated to involve in T cell activity and impair viral infectivity. Recently, high expression levels of Ly6E have been reported in tumor microenvironment (TME) of various types of cancers. However, the immunoregulatory mechanism of Ly6E manipulating TME remains unknown.</p><p><strong>Methods: </strong>TCGA database and Kaplan-Meier plotter database were used to evaluate the correlation between Ly6E expression levels and cancer patient survival. After analyzing Ly6E expression levels in human breast cancer tissues and tumor cell lines, we generated Ly6E knockout (KO) and overexpression (OE) mouse cell lines. Cell proliferation ability in vitro and the ability of growth and metastasis in mouse tumor models were compared between KO/OE and wild-type tumor cells. On day 7 after tumor implantation, tumor tissues were separated for flow cytometric assay, bulk RNA sequencing and single-cell RNA sequencing (ScRNA-seq). The role of Ly6E-expressing tumor cell on macrophage was analyzed in vitro.</p><p><strong>Results: </strong>Our result surprisingly found that high Ly6E expression levels were associated with CD8<sup>+</sup> T cell exclusion in tumor tissues and resistance to immunotherapy. Our data showed that knockout of Ly6E in tumor cells prompts tumor regression and inhibits tumor metastases, and Ly6E-OE tumor cells vice versa. The enhanced anti-tumor effect of Ly6E knockout in tumor cells was dependent on T cell response and formed long-lasting memory. The increase in the CD8<sup>+</sup> T-cell infiltration into the tumor islet of Ly6E-KO tumors confirmed the role of Ly6E on T cell exclusion. ScRNA-seq analysis showed that M2 macrophages are particularly abundant in the Ly6E-expressing tumor tissues, especially M2-4 macrophage cluster identified by high levels of Arg-1, indicates that Ly6E-expressing tumor cells might restrict T cell infiltration via M2 macrophages. Moreover, in vitro assay showed that cell culture media derived from Ly6E-positive tumor cells promoted macrophage migration and M2 polarization.</p><p><strong>Conclusion: </strong>Our study illuminated that Ly6E-expressing tumor cells facilitated the accumulation of M2 macrophages in TME, which contributes to CD8<sup>+</sup> T cell exclusion and provides new insights for improving efficacy of cancer immunotherapy.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 1","pages":"4"},"PeriodicalIF":4.6,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interdependence of coagulation with immunotherapy and BRAF/MEK inhibitor therapy: results from a prospective study. 凝血与免疫疗法和 BRAF/MEK 抑制剂疗法之间的相互依存关系:一项前瞻性研究的结果。
IF 4.6 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2024-11-02 DOI: 10.1007/s00262-024-03850-y
Malte Beckmann, Julian Schlüter, Michael Erdmann, Rafaela Kramer, Sarah Cunningham, Holger Hackstein, Robert Zimmermann, Lucie Heinzerling
{"title":"Interdependence of coagulation with immunotherapy and BRAF/MEK inhibitor therapy: results from a prospective study.","authors":"Malte Beckmann, Julian Schlüter, Michael Erdmann, Rafaela Kramer, Sarah Cunningham, Holger Hackstein, Robert Zimmermann, Lucie Heinzerling","doi":"10.1007/s00262-024-03850-y","DOIUrl":"10.1007/s00262-024-03850-y","url":null,"abstract":"<p><p>Immune checkpoint inhibitor (ICI) therapies effectively treat a broadening spectrum of cancer entities but induce various immune-related side effects (irAEs). Recent reports suggest a correlation between ICI-induced systemic inflammation and thromboembolic events as well as an increased effectiveness by coadministration of anticoagulants. With cancer patients having a higher risk of thrombotic events per se, it is crucial to dissect and characterize the mechanisms that cause pro-coagulative effects induced by systemic tumor therapies and their potential interplay with anti-tumor response. A total of 31 patients with advanced skin cancer treated with either ICIs (n = 24) or BRAF/MEK inhibitors (n = 7) were longitudinally assessed for blood and coagulation parameters before as well as 7, 20 and 40 days after initiation of systemic tumor therapy. Changes were analyzed and compared between both groups. In addition, the influence of coagulation parameters on progression-free, recurrence-free and overall survival was investigated. The ICI cohort presented significantly increased factor VIII activity after one week of therapy (p 0.0225); while, protein S activity was reduced during the whole observation period. Additionally, von Willebrand factor activity and tissue factor concentrations increased under immunotherapy. Similar changes occurred under BRAF/MEK inhibitor therapy (BRAF/MEKi). Increased baseline levels of von Willebrand factor antigen and factor VIII:C before the start of ICI therapy correlated with a significantly higher risk of recurrence for patients receiving adjuvant immunotherapy. The findings suggest the induction of a pro-coagulant state under ICI and BRAF/MEKi and a role of coagulation parameters in the efficacy of ICI therapies.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 1","pages":"5"},"PeriodicalIF":4.6,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to: Efficacy and safety of anti‑PD‑1/PD‑L1‑based dual immunotherapies versus PD‑1/PD‑L1 inhibitor alone in patients with advanced solid tumor: a systematic review and meta‑analysis. 更正:基于抗PD-1/PD-L1的双重免疫疗法与单用PD-1/PD-L1抑制剂对晚期实体瘤患者的疗效和安全性:系统综述和荟萃分析。
IF 4.6 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2024-10-16 DOI: 10.1007/s00262-024-03819-x
Yueying Chen, Hedong Han, Jing Cheng, Qinpei Cheng, Suhua Zhu, Ping Zhan, Hongbing Liu, Yong Song, Tangfeng Lv
{"title":"Correction to: Efficacy and safety of anti‑PD‑1/PD‑L1‑based dual immunotherapies versus PD‑1/PD‑L1 inhibitor alone in patients with advanced solid tumor: a systematic review and meta‑analysis.","authors":"Yueying Chen, Hedong Han, Jing Cheng, Qinpei Cheng, Suhua Zhu, Ping Zhan, Hongbing Liu, Yong Song, Tangfeng Lv","doi":"10.1007/s00262-024-03819-x","DOIUrl":"10.1007/s00262-024-03819-x","url":null,"abstract":"","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"263"},"PeriodicalIF":4.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy and safety of perioperative immunotherapy combinations for resectable non-small cell lung cancer: a systematic review and network meta-analysis. 可切除非小细胞肺癌围手术期免疫疗法组合的疗效和安全性:系统综述和网络荟萃分析。
IF 5.4 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2024-10-09 DOI: 10.1007/s00262-024-03844-w
Yuelin Han, Xiangtian Xiao, Tingting Qin, Shuxi Yao, Xinyue Liu, Yanqi Feng, Zhou Li, Yiming Li, Shu Xia
{"title":"Efficacy and safety of perioperative immunotherapy combinations for resectable non-small cell lung cancer: a systematic review and network meta-analysis.","authors":"Yuelin Han, Xiangtian Xiao, Tingting Qin, Shuxi Yao, Xinyue Liu, Yanqi Feng, Zhou Li, Yiming Li, Shu Xia","doi":"10.1007/s00262-024-03844-w","DOIUrl":"10.1007/s00262-024-03844-w","url":null,"abstract":"<p><strong>Introduction: </strong>Several trials of perioperative immunotherapy for resectable non-small cell lung cancer (NSCLC) reported positive results. They were designed to adjuvant, neoadjuvant and sandwich (neoadjuvant plus adjuvant) immunotherapy with immune checkpoint inhibitors and chemotherapy (CT). The differences between neoadjuvant and sandwich modalities were unclear.</p><p><strong>Method: </strong>We performed a systematic review and Bayesian network meta-analysis by retrieving relevant literature from PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov, WHO ICTRP and major international conferences.</p><p><strong>Results: </strong>We analyzed 8 studies involving 3429 patients, including 6 neoadjuvant plus adjuvant (Neo-Adj) and 2 neoadjuvant (Neo) trials. Neo-Adj had better event-free survival (EFS) (hazard ratio [HR] = 0.57, 95% confidence interval [CI]: 0.45-0.71) than CT. There existed no difference between Neo-Adj and Neo in EFS (HR = 0.87, 95% CI: 0.53-1.46) and overall survival (OS) (HR = 1.04, 95% CI: 0.38-2.57). Neo might have lower incidence of treatment-related adverse events (TRAEs) (relative risk [RR] = 0.96, 95% CI: 0.87-1.12) than Neo-Adj. Subgroup analysis of PD-L1 ≥ 50% suggested that EFS of Neo-Adj (HR = 0.46, 95% CI: 0.27-0.76) and Neo (HR = 0.24, 95% CI: 0.06-0.89) was better than CT, and Neo-Adj potentially caused shorter EFS than Neo (HR = 1.92, 95% CI: 0.46-7.84).</p><p><strong>Conclusions: </strong>Our results suggest that Neo-Adj and Neo have similar EFS for patients with PD-L1 < 1% or 1-49%. However, patients with PD-L1 ≥ 50% may obtain more EFS benefit from Neo than Neo-Adj. Neo might present a more favorable assessment than Neo-Adj when evaluating OS. Moreover, adding adjuvant immunotherapy may increase toxicity.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"262"},"PeriodicalIF":5.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biomarker role of thyroid irAE and PD-L1 positivity in predicting PD-1 blockade efficacy in patients with non-small cell lung cancer. 甲状腺irAE和PD-L1阳性在预测非小细胞肺癌患者PD-1阻断剂疗效中的生物标记作用。
IF 5.4 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2024-10-09 DOI: 10.1007/s00262-024-03852-w
Hye In Kim, Won Gu Kim, Mijin Kim, Nak Gyeong Ko, Mihyeon Jin, Hyun Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Yoon-La Choi, Min Ji Jeon, Tae Yong Kim, Won Bae Kim, Sang-We Kim, Dae Ho Lee, Se Jin Jang, Sun Wook Kim, Jae Hoon Chung, Tae Hyuk Kim, Se-Hoon Lee
{"title":"Biomarker role of thyroid irAE and PD-L1 positivity in predicting PD-1 blockade efficacy in patients with non-small cell lung cancer.","authors":"Hye In Kim, Won Gu Kim, Mijin Kim, Nak Gyeong Ko, Mihyeon Jin, Hyun Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Yoon-La Choi, Min Ji Jeon, Tae Yong Kim, Won Bae Kim, Sang-We Kim, Dae Ho Lee, Se Jin Jang, Sun Wook Kim, Jae Hoon Chung, Tae Hyuk Kim, Se-Hoon Lee","doi":"10.1007/s00262-024-03852-w","DOIUrl":"10.1007/s00262-024-03852-w","url":null,"abstract":"<p><p>Thyroid immune-related adverse events (irAEs) are associated with programmed cell death protein 1 (PD-1) blockade efficacy in non-small cell lung cancer (NSCLC). However, their independence from PD-L1 expression and quantitative impact on predicting PD-1 blockade efficacy remain unexplored. This multicenter, retrospective, longitudinal study from Korea included 71 metastatic NSCLC patients who underwent PD-L1 expression and thyroid function testing during PD-1 blockade. Disease progression by the Response Evaluation Criteria for Solid Tumors was the main outcome. Three-stage analyses were performed: (1) multivariate Cox regression models adjusted for PD-L1 expression according to thyroid irAEs; (2) subgroup analyses; (3) regrouping and comparing predictivity of current and alternative staging. Patients with thyroid irAE + exhibited a longer progression-free survival [7/20 vs. 34/51, adjusted HR 0.19 (0.07-0.47); P < 0.001] than those with thyroid irAE-, independent of PD-L1 expression; the results remained across most subgroups without interaction. The three groups showed different adjusted HR for disease progression (Group 1: PD L1 + and thyroid irAE + ; Group 2: PD-L1 + or thyroid irAE + : 5.08 [1.48-17.34]; Group 3: PD-L1- and thyroid irAE- : 30.49 [6.60-140.78]). Alternative staging (Group 1 in stage IVB → stage IVA; Group 3 in stage IVA → stage IVB) improved the prognostic value (PVE: 21.7% vs. 6.44%; C-index: 0.706 vs. 0.617) compared with the 8th Tumor-Node-Metastasis staging. Our study suggests thyroid irAEs and PD-L1 expression are independent biomarkers that improve predicting PD-1 blockade efficacy in NSCLC. Thyroid irAEs would be helpful to identify NSCLC patients who benefit from PD-1 blockade in early course of treatment.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"260"},"PeriodicalIF":5.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Optimizing cancer classification: a hybrid RDO-XGBoost approach for feature selection and predictive insights. 优化癌症分类:用于特征选择和预测洞察的 RDO-XGBoost 混合方法。
IF 5.4 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2024-10-09 DOI: 10.1007/s00262-024-03843-x
Abrar Yaqoob, Navneet Kumar Verma, Rabia Musheer Aziz, Mohd Asif Shah
{"title":"Optimizing cancer classification: a hybrid RDO-XGBoost approach for feature selection and predictive insights.","authors":"Abrar Yaqoob, Navneet Kumar Verma, Rabia Musheer Aziz, Mohd Asif Shah","doi":"10.1007/s00262-024-03843-x","DOIUrl":"10.1007/s00262-024-03843-x","url":null,"abstract":"<p><p>The identification of relevant biomarkers from high-dimensional cancer data remains a significant challenge due to the complexity and heterogeneity inherent in various cancer types. Conventional feature selection methods often struggle to effectively navigate the vast solution space while maintaining high predictive accuracy. In response to these challenges, we introduce a novel feature selection approach that integrates Random Drift Optimization (RDO) with XGBoost, specifically designed to enhance the performance of cancer classification tasks. Our proposed framework not only improves classification accuracy but also offers valuable insights into the underlying biological mechanisms driving cancer progression. Through comprehensive experiments conducted on real-world cancer datasets, including Central Nervous System (CNS), Leukemia, Breast, and Ovarian cancers, we demonstrate the efficacy of our method in identifying a smaller subset of unique and relevant genes. This selection results in significantly improved classification efficiency and accuracy. When compared with popular classifiers such as Support Vector Machine, K-Nearest Neighbor, and Naive Bayes, our approach consistently outperforms these models in terms of both accuracy and F-measure metrics. For instance, our framework achieved an accuracy of 97.24% in the CNS dataset, 99.14% in Leukemia, 95.21% in Ovarian, and 87.62% in Breast cancer, showcasing its robustness and effectiveness across different types of cancer data. These results underline the potential of our RDO-XGBoost framework as a promising solution for feature selection in cancer data analysis, offering enhanced predictive performance and valuable biological insights.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 12","pages":"261"},"PeriodicalIF":5.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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