Translational lung cancer research最新文献

{"title":"Construction of a checkpoint inhibitor-related pneumonia diagnostic model based on exhaled nitric oxide: a prospective observational study.","authors":"Yimei Gao, Tingyue Luo, Danhui Huang, Zeyu Fu, Shudong Ma, Li Lin, Haohua Huang, Tiantian Liu, Jinming Zhang, Xiaoxiao Jiang, Yanmei Ye, Junwei Chen, Junjie Xi, Jinzhong Zhuo, Kaijun Chen, Jingqi Ai, Laiyu Liu, Shaoxi Cai, Hangming Dong","doi":"10.21037/tlcr-2024-1085","DOIUrl":"10.21037/tlcr-2024-1085","url":null,"abstract":"<p><strong>Background: </strong>Checkpoint inhibitor-related pneumonia (CIP) is a complication of immune checkpoint inhibitors (ICIs) with high mortality. There is still a lack of effective biomarkers to identify CIP. Exhaled nitric oxide (eNO), an airway inflammatory marker, can be obtained by non-invasive methods, but its value in CIP is unknown. The purpose of this study was to investigate the value of eNO in CIP.</p><p><strong>Methods: </strong>Lung cancer patients who received ICIs were included at Nanfang Hospital, Southern Medical University. Fractional eNO at expiratory flow rates of 50 and 200 mL/s (FeNO50 and FeNO200) were measured. The alveolar concentration of nitric oxide (CaNO) was calculated based on the two-compartment model of airway and alveoli. The optimal CaNO cut-off value was determined by the receiver operating characteristic (ROC) curve. eNO, clinical characteristics, and laboratory tests were analyzed to find out the risk factors for CIP by logistic regression analysis. A multi-indicator model based on best risk factors for CIP was developed and internally validated.</p><p><strong>Results: </strong>CaNO was significantly elevated in the CIP group [8.1±5.0 <i>vs</i>. 4.9±3.1 parts per billion (ppb), P<0.001]. The area under the curve (AUC) of CaNO to differentiate CIP was 0.728 [95% confidence interval (CI): 0.670-0.786; P=0.001]. The best cut-off value of CaNO was 6.350 ppb. Increased CaNO [odds ratio (OR), 1.30; 95% CI: 1.19-1.43; P<0.001], emphysema reported on chest computed tomography (CT) (OR, 2.54; 95% CI: 1.41-4.60), a small amount of pleural effusion reported on chest CT (OR, 2.48; 95% CI: 1.37-4.50), pre-existing radiotherapy (OR, 3.89; 95% CI: 1.96-7.73) and the lower counts of lymphocyte cell in peripheral blood (OR, 0.69; 95% CI: 0.44-1.10) were independently associated with CIP. The five factors were incorporated into a multi-indicator model with a good predictive accuracy of 0.821.</p><p><strong>Conclusions: </strong>CaNO may be a new marker for identifying CIP. Increased CaNO, pre-existing radiotherapy and emphysema reported on chest CT, a small amount of pleural effusion reported on chest CT, and lower count of lymphocyte cell in peripheral blood are independently associated with CIP.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 5","pages":"1740-1755"},"PeriodicalIF":4.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326945","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}

{"title":"Opportunities and challenges in lung cancer care in the era of large language models and vision language models.","authors":"Yi Luo, Hamed Hooshangnejad, Wilfred Ngwa, Kai Ding","doi":"10.21037/tlcr-24-801","DOIUrl":"10.21037/tlcr-24-801","url":null,"abstract":"<p><p>Lung cancer remains the leading cause of cancer-related deaths globally. Over the past decade, the development of artificial intelligence (AI) has significantly propelled lung cancer care, particularly in areas such as lung cancer early diagnosis, survival prediction, recurrence prediction, medical image processing, medical image registration, medical visual question answering, clinical report writing, medical image generation, and multimodal integration. This review aims to provide a comprehensive summary of the various AI methods utilized in lung cancer care, with a particular emphasis on machine learning and deep learning techniques. Moreover, with the advent and widespread application of large language models (LLMs), vision language models (VLMs), and multimodal integration for downstream clinical tasks, we explore the current landscape these cutting-edge AI tools offer. However, it also presents both significant challenges and opportunities, including data privacy risks, inherent biases that may exacerbate healthcare disparities, model hallucinations, ethical implications, implementation costs, and the lack of standardized evaluation metrics. Furthermore, the translation of these technologies from experimental research to clinical implementation demands comprehensive validation protocols and multidisciplinary collaboration to guarantee patient safety, therapeutic efficacy, and equitable healthcare delivery. This review emphasizes the critical role of AI in enhancing our understanding and management of lung cancer, ultimately striving for precision medicine and equitable healthcare worldwide.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 5","pages":"1830-1847"},"PeriodicalIF":4.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326957","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}

{"title":"Effect of the number of induction chemotherapy cycles on the efficacy of first-line atezolizumab combined with chemotherapy in extensive-stage small cell lung cancer.","authors":"Mengxing You, Jiayu Liu, Fei Teng, Lige Wu, Haifeng Qin, Yan Zhang, Cuiying Zhang, Ziling Liu, Kewei Ma, Esteban C Gabazza, Jacopo Vannucci, Xuezhi Hao, Junling Li, Puyuan Xing","doi":"10.21037/tlcr-2025-207","DOIUrl":"10.21037/tlcr-2025-207","url":null,"abstract":"<p><strong>Background: </strong>Compared with chemotherapy alone, the addition of atezolizumab to the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) improves the overall survival (OS), but the benefit remains limited. This study aims at investigating the factors influencing prognosis and to assess the effect of the number of induction chemotherapy cycles on treatment efficacy.</p><p><strong>Methods: </strong>We retrospectively analyzed the data of patients with ES-SCLC treated in five centers between March 2020 and September 2022. All 45 patients received first-line treatment with etoposide plus platinum combined with atezolizumab. The primary endpoints were progression-free survival (PFS) and OS in the total population and subpopulations based on the number of induction chemotherapy cycles. Least absolute shrinkage and selection operator (LASSO) regression were applied to identify the prognostic variables, and the effect of varying the number of induction chemotherapy cycles on the treatment efficacy was evaluated.</p><p><strong>Results: </strong>A total of 45 patients were enrolled in the study. The median PFS for the first-line treatment was 7 months, and the median OS was 17.6 months. The following 10 variables were analyzed using LASSO regression: gender, age, liver metastasis, bone metastasis, brain metastasis, number of first-line induction chemotherapy cycles, first-line immunotherapy maintenance, receipt of cross-line immunotherapy, chest radiotherapy, and brain radiotherapy. The analysis revealed that receiving ≥6 cycles of induction chemotherapy was the most important variable affecting prognosis and the only one significant [concordance index: 0.658; hazard ratio: 0.32 (95% confidence interval: 0.17-0.63)]. Patients who received ≥6 cycles of induction chemotherapy (n=25) had a longer median PFS (8 <i>vs.</i> 5 months) and median OS (18.5 <i>vs.</i> 13.1 months) than those who received <6 cycles (n=20). Subgroup analyses indicated consistent survival benefits of ≥6 induction chemotherapy cycles across key subgroups, including males, patients aged ≤65 years, and those with or without brain metastasis (all P value <0.05).</p><p><strong>Conclusions: </strong>Receiving ≥6 cycles of induction chemotherapy significantly prolonged the median PFS and median OS of patients, highlighting its crucial factor influencing the efficacy of first-line atezolizumab combined with chemotherapy in patients with ES-SCLC.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1408-1417"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094799","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}

{"title":"Multidisciplinary international expert consensus on perioperative airway management.","authors":"Hengrui Liang, Guowei Che, Fei Cui, Junguo Dong, Weiquan Gu, Chundong Gu, Shun Xu, Yufeng Ba, Kaican Cai, Qingdong Cao, Chang Chen, Chun Chen, Qixun Chen, Liyang Cheng, Gang Feng, Yunjiu Gou, Wenwei Guo, Jinxi He, Junming He, Jian Hu, Ying Huang, Wenxi Wang, Wenjie Jiao, Shunjun Jiang, Jun Liu, Lan Lan, Wei Li, Xiaofei Li, Zhongcheng Li, Yin Li, Zhu Liang, Hongxu Liu, Yingbin Liu, Xinyu Mei, Xicheng Song, Daqiang Sun, Hui Tian, Ziqiang Tian, Jianhua Wang, Guangsuo Wang, Xin Xu, Xudong Xiang, Guobing Xu, Tao Xue, Chao Yang, Xiaolong Yan, Nuo Yang, Feng Yao, Dalong Yin, Xiaochuan Yin, Bentong Yu, Wei Zhai, Yu Zhang, Guangjian Zhang, Xiaowen Zhang, Qiang Zhang, Yi Zhang, Jun Zhao, Haihui Zhong, Alessandro Brunelli, Till Ploenes, Luca Bertolaccini, John Kit Chung Tam, Min P Kim, Majed Refai, Michel Gonzalez, Adam R Dyas, Nicoletta Pia Ardò, Hiran C Fernando, Giulio Maurizi, Gregor J Kocher, Giuseppe Marulli, Álvaro Fuentes-Martín, Gianluca Perroni, Kyung Soo Kim, Maria Rodriguez, Marcus Taylor, Xusen Zou, Wei Wang, Jianxing He","doi":"10.21037/tlcr-2025-273","DOIUrl":"10.21037/tlcr-2025-273","url":null,"abstract":"<p><strong>Background: </strong>Perioperative airway management is critical for patient safety and optimal surgical outcomes. Effective airway management reduces postoperative pulmonary complications and accelerates recovery. This expert consensus aims to update the earlier consensus based on the latest research and emphasize aspects that were previously overlooked.</p><p><strong>Methods: </strong>A comprehensive search up to June 2024 was performed. Earlier consensus documents were reviewed to ensure thorough coverage. A modified Delphi method involved 62 domestic experts from various surgical and anesthetic specialties who discussed and voted on preliminary recommendations in face-to-face meetings, requiring ≥70% agreement. Drafts were then reviewed by 18 international experts via email to incorporate diverse insights.</p><p><strong>Results: </strong>Through the modified Delphi method, consensus was achieved with ≥70% agreement among the 62 domestic experts, ensuring that the preliminary recommendations were robust and widely supported. Additionally, feedback from the 18 international experts provided diverse insights that further refined and validated the recommendations. Recommendations were established for preoperative airway preparation, anesthesia management, surgical approach, postoperative airway management, and managing coexisting respiratory diseases. These recommendations update the perspectives of earlier consensus documents based on the latest research and emphasize non-intubated surgery, inhalation therapy, and individualized treatment for patients with coexisting pulmonary diseases.</p><p><strong>Conclusions: </strong>This expert consensus provides a valuable reference for clinical practice. Further technological optimization and clinical research are needed to improve perioperative airway management.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1042-1060"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094881","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}

{"title":"Molecular heterogeneity of small cell lung cancer and new therapeutic possibilities: a narrative review of the literature.","authors":"Valeria Cognigni, Ilaria Toscani, Simona D'Agnelli, Federica Pecci, Luisella Righi, Rossana Berardi, Marcello Tiseo","doi":"10.21037/tlcr-24-755","DOIUrl":"10.21037/tlcr-24-755","url":null,"abstract":"<p><strong>Background and objective: </strong>Small cell lung cancer (SCLC) is an aggressive disease commonly occurring in individuals with a history of heavy smoking. Despite recent approvals of chemotherapy and immunotherapy in the first-line treatment of extensive-stage SCLC, it maintains a poor prognosis. Moreover, only a small percentage of patients benefits from the addition of immunotherapy to platinum-based chemotherapy. The lack of significant progress in therapeutic options unrevealed the urgent need for a deeper understanding of tumor biology and easy-to-use predictive biomarkers, aiming to better tailor the treatment strategy. The aim of this review is to summarize recent evidence about the biology, molecular heterogeneity, as well as tumor microenvironment (TME) of SCLC and their forefront therapeutic implications.</p><p><strong>Methods: </strong>A literature search was conducted using PubMed, focusing on articles published in English from 1981 to October 2024. Studies on SCLC biology and subclassification were selected for further analysis and integrated in the current narrative review.</p><p><strong>Key content and findings: </strong>SCLC entity implies four distinct molecular subtypes based on transcription factors expression, specifically achaete-scute homolog 1 (ASCL1), neurogenic differentiation 1 (NEUROD1), POU class 2 homeobox 3 (POU2F3), and yes-associated protein 1 (YAP1), reflecting the tumor heterogeneity in terms of gene expression, transcriptional profiles, immune infiltration, and treatment sensitivity. Recently, a new subgroup, \"SCLC-I\", has been proposed to replace the YAP1 subtype, showing higher responsiveness to immunotherapy. The TME, implying immune cell infiltration and their interactions with cancer cells, plays a crucial role in determining SCLC's sensitivity to immunotherapy.</p><p><strong>Conclusions: </strong>Advances in SCLC molecular characterization and the development of targeted therapies against specific molecular pathways might improve patients' clinical outcome, supporting a more personalized approach to this complex disease.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1441-1455"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094955","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}

{"title":"Diagnostic accuracy of serum biomarkers MMP11 and SPP1 in non-small cell lung cancer: an analysis of sensitivity, specificity, and area under the curve.","authors":"Minha Lea Yoon, Sang Yean Kim, Hyelim Chun, Jina Park, Woo-Jeong Seo, Jung Young Lee, Jung Hwan Yoon","doi":"10.21037/tlcr-2024-1068","DOIUrl":"10.21037/tlcr-2024-1068","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) represents the vast majority of lung cancer cases, comprising 80-85% of all diagnoses, and continues to be a primary contributor to cancer-related deaths. Early detection is essential for improving patient outcomes, yet current diagnostic markers lack both sensitivity and specificity. This study aims to identify novel biomarkers that could enhance early diagnosis.</p><p><strong>Methods: </strong>We conducted a comprehensive gene expression analysis of three NSCLC datasets (GSE33479, GSE18842, and GSE32863) and identified seven genes with relevance to the extracellular region and space: <i>MMP11</i>, <i>SPP1</i>, <i>ERO1L</i>, <i>CTHRC1</i>, <i>SPINK1</i>, <i>LAD1</i>, and <i>SFN</i>. We further assessed these markers through serum protein analysis involving 200 NSCLC patients and 200 healthy controls, employing receiver operating characteristic (ROC) curve analysis to evaluate their diagnostic efficacy.</p><p><strong>Results: </strong>Among the identified genes, <i>MMP11</i> and <i>SPP1</i> exhibited significant upregulation and strong discriminatory power in NSCLC tissues, achieving area under the curve (AUC) values exceeding 0.9. Serum protein levels of MMP11 and SPP1 were significantly higher in NSCLC patients compared to healthy controls. ROC curve analysis confirmed the diagnostic potential of MMP11 (AUC: 0.9896) and SPP1 (AUC: 0.9053), both outperforming the existing marker carcinoembryonic antigen (CEA) (AUC: 0.7109). MMP11 demonstrated sensitivity of 94.53% and specificity of 94.97%, while SPP1 showed sensitivity of 83.17% and specificity of 83.84%. In contrast, CEA exhibited a sensitivity of 66.83% and specificity of 67.69%.</p><p><strong>Conclusions: </strong>The results indicate that MMP11 and SPP1, detectable in serum, may serve as valuable non-invasive biomarkers for the early diagnosis of NSCLC, particularly within health screening contexts. However, further research within larger and more diverse cohorts is imperative to validate these biomarkers and investigate the mechanisms underlying MMP11 and SPP1 expression in NSCLC. This study highlights the potential of these biomarkers to enhance diagnostic accuracy and improve patient outcomes in NSCLC.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1197-1211"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094241","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}

{"title":"Impact of immune-related adverse events on clinical outcomes in patients with advanced non-small cell lung cancer with low PD-L1 expression, focusing on pneumonitis: a multicenter retrospective study in Japan.","authors":"Shiho Goda, Tadaaki Yamada, Kenji Morimoto, Tae Hata, Yasuhiro Goto, Akihiko Amano, Yoshiki Negi, Satoshi Watanabe, Naoki Furuya, Tomohiro Oba, Tatsuki Ikoma, Akira Nakao, Keiko Tanimura, Hirokazu Taniguchi, Akihiro Yoshimura, Tomoya Fukui, Daiki Murata, Kyoichi Kaira, Shinsuke Shiotsu, Asuka Okada, Makoto Hibino, Yusuke Chihara, Takashi Kijima, Koichi Takayama","doi":"10.21037/tlcr-2024-1177","DOIUrl":"10.21037/tlcr-2024-1177","url":null,"abstract":"<p><strong>Background: </strong>Severe immune-related adverse events (irAEs) are often associated with combined immunotherapy and chemotherapy in patients with non-small cell lung cancer (NSCLC). However, their effect on clinical outcomes has yet to be fully elucidated. In this study, we investigated the impact of irAEs, particularly pneumonitis, on clinical outcomes in patients receiving combined immunotherapy and chemotherapy for NSCLC.</p><p><strong>Methods: </strong>We retrospectively enrolled 850 patients with programmed cell death ligand-1 (PD-L1) 1-49% advanced NSCLC who were treated with chemotherapy alone or with combined immunotherapy and chemotherapy as first-line treatment at 19 different institutions in Japan between March 2017 and June 2022. Using data from their medical records, we examined the type and severity of irAEs and their association with clinical outcomes, including overall survival (OS) and progression-free survival (PFS).</p><p><strong>Results: </strong>OS and PFS were not significantly different between patients with and without severe irAEs. However, in the group receiving combined immunotherapy and chemotherapy, those who developed pneumonitis within 42 days of treatment initiation had shorter OS and PFS, irrespective of the pneumonitis grade, and a worse prognosis than those who received chemotherapy alone. Additionally, early-onset pneumonitis was more likely in patients aged >75 years, those with high lactate dehydrogenase levels, and those receiving steroids or immunosuppressants, suggesting that these factors may contribute to the risk of early-onset pneumonitis.</p><p><strong>Conclusions: </strong>Early-onset pneumonitis is a poor prognostic factor in patients with PD-L1 1-49% advanced NSCLC receiving combined immunotherapy and chemotherapy. Further large-scale observational studies are warranted to confirm these findings.</p><p><strong>Keywords: </strong>Non-small cell lung cancer (NSCLC); severe immune-related adverse events (irAEs); pneumonitis.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1185-1196"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094872","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}

{"title":"Nanoassemblies loaded with low-dose paclitaxel can enhance the response of lung cancer immunotherapy by activating dendritic cells.","authors":"Jianlin Long, Dairong Li, Wei Zhao, Guanzhong Liang, Lumi Huang, Shuangyi Lei, Yan Li","doi":"10.21037/tlcr-2025-180","DOIUrl":"10.21037/tlcr-2025-180","url":null,"abstract":"<p><strong>Background: </strong>The immune tolerance of the tumor immune microenvironment (TIME) restricts the response to immune checkpoint inhibitors (ICIs). Targeted activation of dendritic cells (DCs) in the TIME seems to be a scheme for improving the therapeutic effect of ICIs treatment. The purpose of this study was to utilize nanotechnology to reprogram the immunosuppressive tumor immune microenvironment <i>in situ</i>, improving the response of ICIs to lung cancer.</p><p><strong>Methods: </strong>In this study, a folic acid (FA)-modified nanoassembly (NA) loaded with low-dose paclitaxel (PTX) (FA-PTX NA), self-assembled by distearoylphosphatidylethanolamine-methoxy polyethylene glycol 2000-folic acid (DSPE-mPEG2000-FA) and PTX, was designed to reprogram the DC function of the TIME to sensitize cells to cancer immunotherapy. The characteristics of FA-PTX NAs were studied, and the cytotoxicity, cellular uptake, and DC stimulation of FA-PTX NAs were evaluated <i>in vitro</i> using a Lewis lung carcinoma (LLC) cell line and bone marrow-derived cells (BMDCs). Following this, the effect of the reprogrammed TIME and on the sensitization to immunotherapy <i>in vivo</i> were examined in a C57BL/6 mouse LLC subcutaneous xenograft model.</p><p><strong>Results: </strong>The prepared FA-PTX NAs exhibited a slightly negative surface charge, appropriate size and shape, good drug release profiles, and high drug encapsulation efficiency and blood compatibility. The FA-PTX NAs were effectively uptaken by bone BMDCs, increasing the activation and expression of the costimulatory factor of BMDCs <i>in vitro</i>. In the LLC xenograft model treated with intravenous injection of FA-PTX NAs, the numbers of CD4⁺ and CD8⁺ T cells in the TIME increased significantly, the killing activity of tumor-specific cytotoxic T lymphocytes (CTLs) was significantly enhanced, and at the same time, the concentration of transforming growth factor β (TGF-β) decreased significantly. Furthermore, the infiltrated CD8⁺ T cells in TIME were mainly distributed in the tumor parenchyma. The combination of FA-PTX NAs and ICIs effectively inhibited the growth of LLC xenograft tumor, demonstrating a greater effect than that of ICIs alone. Moreover, it was found that apoptosis induction, increase in CD4⁺ and CD8⁺ T-cell infiltration, and improvement in the distribution of CD8⁺ T cells were involved in the anticancer mechanism of this combination treatment.</p><p><strong>Conclusions: </strong>The NA loaded with low-dose PTX can reprogram the DC function in the TIME and exert a synergistic anticancer effect with ICIs in lung cancer treatment. Increased sensitization to ICI therapy as stimulated by PTX-enhanced NAs has potential applications in lung cancer immunotherapy.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1418-1440"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094888","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}

{"title":"Comparing neutrophil-to-lymphocyte ratio (NLR), absolute neutrophil count (ANC) and derived NLR as predictive biomarkers in first-line immunotherapy for non-small cell lung cancer: a retrospective study.","authors":"Elise Longueville, Maxime Dewolf, Véronique Dalstein, Anne Durlach, Alexandre Vivien, Béatrice Nawrocki-Raby, Myriam Polette, Gaëtan Deslée, Julien Ancel","doi":"10.21037/tlcr-24-808","DOIUrl":"10.21037/tlcr-24-808","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer, especially non-small cell lung cancer (NSCLC), poses a significant global health challenge due to its high prevalence and poor prognosis despite treatment advancements, including immunotherapy. While programmed death-ligand 1 (PD-L1) expression is a commonly used biomarker, its limitations justify exploration of alternative markers like the neutrophil-to-lymphocyte ratio (NLR), absolute neutrophil count (ANC) and derived NLR (dNLR). This retrospective study aims to directly compare NLR, ANC and dNLR as predictive biomarkers in first-line NSCLC immunotherapy, shedding light on their prognostic implications and potential clinical utility.</p><p><strong>Methods: </strong>This retrospective single-center study included 70 consecutive patients diagnosed with metastatic NSCLC, treated in first-line with immune checkpoint inhibitors (ICIs) between September 2015 and March 2023 at the University Hospital of Reims, France. Baseline clinical characteristics and hematological values were collected, and survival analysis, including progression-free survival (PFS) and overall survival (OS), was performed based on RECIST (Response Evaluation Criteria in Solid Tumors) criteria. NLR and dNLR were calculated, and their predictive performances were assessed.</p><p><strong>Results: </strong>Baseline characteristics revealed a median age of 65.5 years, predominantly adenocarcinoma histology (82.9%), and high PD-L1 expression (≥50%) in 61.4% of cases. Neither NLR, ANC nor dNLR showed significant associations with known clinical outcome influencers like age, PD-L1 expression, or performance status, but dNLR correlated significantly with initial response (P=0.02). While NLR ≥5 was significantly associated with shorter PFS and OS (P=0.03 and P<0.001, respectively), dNLR >2.5 (P=0.008) or ANC >7.5 (P=0.02) showed significance in predicting poorer OS only. Optimal cut-off values were determined as 5.0 for NLR [area under the curve (AUC) =0.570], 9.00 for ANC (AUC =0.683) and 2.496 for dNLR (AUC =0.610) for OS prediction. Cox regressions revealed no significant association between either biomarker and clinical or histological cofactors. Subgroup analyses suggested NLR's predictive consistency across various subgroups, whereas dNLR and ANC showed limited performance. Both biomarkers demonstrated significant association with OS in patients exposed to ICI alone, but not with chemotherapy combination.</p><p><strong>Conclusions: </strong>The results underscore the potential of NLR as a predictor of survival and progression in NSCLC patients treated with immunotherapy, while dNLR and ANC demonstrate more limited interest. However, larger prospective studies are needed to confirm these observations and further elucidate their clinical utility.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1212-1230"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095007","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}

{"title":"Predictive value of the monocyte-to-high-density lipoprotein ratio in the prognosis of non-small cell lung cancer patients after surgery.","authors":"Yi Liu, Wen-Long Zhang, Song-Ping Cui, Aimée J P M Franssen, Erik R de Loos, Yuichiro Ueda, Takahiro Homma, James Shahoud, Qing Zhao, Yang Gu, Yi-Li Fu, Bin Hu","doi":"10.21037/tlcr-2025-171","DOIUrl":"10.21037/tlcr-2025-171","url":null,"abstract":"<p><strong>Background: </strong>Due to the poor prognosis of non-small cell lung cancer (NSCLC) patients, precise and reliable biomarkers are urgently needed to predict the prognosis in NSCLC patients after radical lung surgery. Hence, this study sought to investigate the correlation between the monocyte-to-high-density lipoprotein ratio (MHR) and overall survival (OS) in NSCLC patients after surgery.</p><p><strong>Methods: </strong>This retrospective study analyzed clinical data, including MHR, from NSCLC patients undergoing radical surgery. OS was calculated to evaluate the prognosis of the NSCLC patients. The association between the MHR and OS was analyzed. A receiver operating characteristic (ROC) curve analysis was conducted to evaluate the 3- and 5-year predictive value of the MHR for prognosis after surgery.</p><p><strong>Results: </strong>In total, 256 patients were enrolled in this study. All patients had a follow-up for more than 5 years. The prognosis of the patients with a higher MHR (>0.3) was worse than that of the patients with a lower MHR (≤0.3) (P<0.001). The univariate Cox survival analysis showed that the MHR, surgery time, tumor (pT) stage, lymph node (pN) stage, and sex were all significantly associated with the risk of death in patients with NSCLC. The multivariate Cox survival analysis showed that the MHR [hazard ratio (HR) =24.837, 95% confidence interval (CI): 7.265-84.911], T stage, N stage, and surgery time were prognostic factors for NSCLC patients after surgery. The stratified analysis, which excluded patients with tumors <i>in situ</i>, showed that the MHR (HR =27.097, 95% CI: 8.081-90.877), surgery time, and pN stage significantly increased the risk of death in NSCLC patients. The area under the ROC curve (AUCROC) values of the MHR in predicting the 3- and 5-year survival of the NSCLC patients after surgery were 0.758 and 0.760, respectively.</p><p><strong>Conclusions: </strong>The MHR was found to be an independent predictor of OS in NSCLC patients after radical surgery. Early monitoring and reducing the MHR may be of great significance in preventing disease recurrence and improving patient prognosis.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1340-1350"},"PeriodicalIF":4.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095011","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}