Translational lung cancer research最新文献

{"title":"Enhancing the sensitivity of lung adenocarcinoma to immune therapeutic agents through <i>SPRED1</i>.","authors":"Chen Wu, Lingling Ma, Yi Wang, Joanna Bidzińska, Yilang Wang","doi":"10.21037/tlcr-2025-800","DOIUrl":"10.21037/tlcr-2025-800","url":null,"abstract":"<p><strong>Background: </strong>Programmed death-ligand 1 (PD-L1), a classic immune checkpoint, is a key target for immunotherapy. Research has demonstrated that Sprouty-related <i>EVH1</i> domain-containing 1 (<i>SPRED1</i>), a negative regulator of the mitogen-activated protein kinase (MAPK) pathway, modulates PD-L1 expression and exhibits antitumor activity in diverse cancers. This study aimed to investigate the role and mechanisms of <i>SPRED1</i> in enhancing the sensitivity of lung adenocarcinoma (LUAD) to immunotherapy and develop novel clinical therapeutic sensitization strategies.</p><p><strong>Methods: </strong>In this study, bioinformatics technologies were employed to examine the interaction between <i>SPRED1</i> and the survival prognosis of patients with LUAD and to identify key interacting molecules of <i>SPRED1</i>. The expression levels of <i>SPRED1</i> in LUAD tissues were measured by tissue staining, Western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier analysis was used to confirm the correlation between <i>SPRED1</i> and the prognosis of patients with LUAD. Moreover, Cell Counting Kit-8 (CCK-8), colony formation, wound healing, and Transwell assays were conducted to investigate the effects of <i>SPRED1</i> on LUAD cell function and immunotherapy.</p><p><strong>Results: </strong>Bioinformatics analyses revealed that <i>SPRED1</i> had a low expression in patients with LUAD and was associated with poor prognosis (P<0.05), suggesting its prominent role in LUAD. Tissue staining, Western blotting, and qRT-PCR demonstrated that <i>SPRED1</i> was downregulated in LUAD tissues, and its low expression was significantly correlated with poor N stage and advanced pathological stage (P<0.05). Transwell, wound healing, and colony formation assays indicated that <i>SPRED1</i> suppressed LUAD cell migration and proliferation. Furthermore, the CCK-8 assay confirmed that <i>SPRED1</i> increases immunotherapeutic sensitivity.</p><p><strong>Conclusions: </strong><i>SPRED1</i> is downregulated in patients with LUAD and is an independent prognostic factor. <i>SPRED1</i> enhances PD-L1 expression, thereby mediating its role in enhancing immunotherapeutic sensitivity in LUAD.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 8","pages":"3076-3089"},"PeriodicalIF":3.5,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065646","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":"The role of perioperative chemoimmunotherapy in resectable non-small cell lung cancer: insights from the NADIM trial.","authors":"Amira de Koning, Ilias Houda, Ezgi B Ulas, Idris Bahce","doi":"10.21037/tlcr-2025-364","DOIUrl":"10.21037/tlcr-2025-364","url":null,"abstract":"","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2383-2386"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837817","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":"Association of cholesterol and triglyceride levels with the recurrence of early-stage lung adenocarcinoma with micropapillary pattern.","authors":"Si Liang, Qinglin Wang, Zi Wang, Xuming Song, Gaochao Dong, Qixing Mao, Feng Jiang","doi":"10.21037/tlcr-2025-118","DOIUrl":"10.21037/tlcr-2025-118","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer remains the predominant cause of cancer-related mortality, with adenocarcinoma being the most prevalent histological subtype. Within our nation, lung adenocarcinoma (LUAD) exhibits the highest incidence and mortality rates among all malignant neoplasms. Specifically, the micropapillary subtype of adenocarcinoma is characterized by particularly poor prognosis and significantly reduced survival rate. Accumulated evidence from prior investigations has identified the micropapillary subtype of LUAD as a high-risk factor for distant metastasis and local recurrence. Nevertheless, the precise correlation between postoperative alterations in cholesterol levels, triglyceride levels and the prognosis of patients with micropapillary LUAD remains to be elucidated. This study aimed to the identify factors influencing postoperative metastatic and recurrence in patients with LUAD with micropapillary pattern (MPP).</p><p><strong>Methods: </strong>A retrospective analysis of 261 patients with MPP and 658 without MPP was conducted, with postoperative pathological analysis determining the MPP. The patients were divided into recurrence (n=58) and non-recurrence (n=203) groups. Postoperative pathological analysis determined the content of micropapillary components in each LUAD case. Patients were categorized into a positive recurrence group (n=58) and a negative recurrence group (n=203). Univariate analyses, logistic multivariate analyses, and survival analyses were performed on the clinical data.</p><p><strong>Results: </strong>Univariate and multivariate analyses revealed that high MPP, tumor size, and abnormal total cholesterol (TC) and triglyceride levels were independent risk factors for recurrence in patients with MPP but not in patients of pattern without it. Survival analysis showed that abnormal cholesterol and triglyceride levels are risk factors for a poor prognosis in patients with MPP. Additionally, a scoring system was developed to identify high-risk patients among those with MPP.</p><p><strong>Conclusions: </strong>Abnormal cholesterol levels and abnormal triglyceride levels are high-risk factors for postoperative recurrence and metastasis in patients with LUAD containing micropapillary components. However, for patients with LUAD that does not contain micropapillary components in the postoperative pathology, there is no significant correlation between prognosis and abnormal cholesterol levels or triglyceride levels.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2437-2451"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837846","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":"Incidence and risk factors of pneumonitis in ALK-rearranged non-small cell lung cancer patients treated with alectinib and thoracic radiotherapy.","authors":"Yiyue Xu, Wenting Qie, Xiao Zhong, Butuo Li, Linlin Yang, Bing Zou, Linlin Wang, Jinming Yu","doi":"10.21037/tlcr-2025-107","DOIUrl":"10.21037/tlcr-2025-107","url":null,"abstract":"<p><strong>Background: </strong>Alectinib and thoracic radiotherapy (TRT) are important modalities in the management of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC), both of which can cause treatment-related pneumonitis (TRP), a serious adverse effect. We therefore aimed to assess the incidence and risk factors of TRP, when these two treatments were combined and to guide the medical decisions.</p><p><strong>Methods: </strong>Patients with ALK-rearranged NSCLC, receiving alectinib and TRT from January 2018 to December 2023 were reviewed, and the clinical and dosimetric data were collected. Logistic regression analyses were performed to evaluate risk factors associated with TRP. The prediction ability of dosimetric parameters for TRP was examined by receiver-operating characteristic (ROC) curve analyses.</p><p><strong>Results: </strong>Of the 62 enrolled patients, 39 (62.9%) developed TRP, and 22 (35.5%) developed grade 2 or higher TRP. Logistic regression analyses revealed age [odds ratio (OR) =1.103, 95% confidence interval (CI): 1.027-1.185, P=0.007], tumor location (OR =0.170, 95% CI: 0.035-0.816, P=0.03), duration of alectinib use (OR =1.006, 95% CI: 1.002-1.011, P=0.006), and total lung V30 (OR =1.149, 95% CI: 1.040-1.269, P=0.006) to be risk factors for TRP. After developing TRP, 35 patients recovered or improved, but one patient died due to respiratory failure.</p><p><strong>Conclusions: </strong>The combined use of alectinib and TRT significantly increased the risk of TRP. Clinicians should consider the elevated risks and related dosimetric factors when deciding on combination treatment for ALK-rearranged NSCLC patients.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2723-2735"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837861","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":"Immunotherapy with lymphocytes derived from banked tumor tissue in two refractory NSCLC patients with leptomeningeal metastases: a report of two cases.","authors":"Ai-Hong Zheng, Chong Yu, Yong-Rui Su, Min Peng, Jian-Yuan Chen, Fu-Wei Wang, Xiu-Ming Zhu, Pei-Yuan Yan, Hai-Tao Wang, Jian Shen, Wei-Jun Chen, Qiang Li, Yuan Chen, Yi Chen, Yin-Shuang Wang, Hang-Yu Gu, Zhuo-Nan Meng, Jing-Wen Zhao, Wan-Mao Ni, Tian-Hua Wang, Sheng-Lian Wu, Min Li, Zheng Wang, Ai-Ping Cheng, Xiao-Xian Huang, Zi-Yan Yang, Jia-Hong Jiang, Qun-Jiang Wang, Jing Qu, Shi-Tai Zhang, Ke-Ke Shi, Hua-Xin Zhang, Da-Hong Zhang, Guo-Qing Wu","doi":"10.21037/tlcr-2025-274","DOIUrl":"10.21037/tlcr-2025-274","url":null,"abstract":"<p><strong>Background: </strong>Cancer patients relapsing with leptomeningeal metastases (LM) but without extracranial lesions are usually unsuitable for cellular immunotherapy with tumor-infiltrating lymphocytes (TILs) owing to lack of tumor tissue. TILs generated from heavily pretreated patients, especially those with non-melanoma cancer often have anergic effects and are less toxic to tumors, limiting the antitumor efficacy of lymphocyte-based therapy. Whether using autologous tumor tissue banked in advance addresses the dilemma has not been explored.</p><p><strong>Case description: </strong>We present two cases of non-small cell lung cancer (NSCLC) who relapsed with LM but without extracranial lesions for whom TIL therapy is otherwise unsuitable. Using autologous tumor tissue banked in advance when they initially underwent tumor resection, we successfully generated therapeutic TILs of which the enhancer of zeste homolog 2 (EZH2) activity was further inhibited in regulatory T cells (Tregs). One case received autologous TILs prepared from a cryopreserved pathological complete response lesion and achieved a complete remission of LM that was ongoing till the preparation of this manuscript. The other case was treated with autologous TILs derived from a cryopreserved treatment-naïve tumor tissue and only achieved a transient response manifested by short-term decrease of circulating tumor deoxyribonucleic acid and serum carcinoembryonic antigen.</p><p><strong>Conclusions: </strong>TILs generated from treatment-responsive lesions and underwent inhibition of EZH2 activity in Tregs have high antitumor efficacy and the banking in advance of treatment-responsive tumor tissue potentially provides a safe and effective adoptive cell therapy (ACT) with TILs for refractory NSCLC patients with LM for whom TIL therapy is otherwise unsuitable.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2880-2890"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837860","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":"Reducing radiation pneumonitis in lung cancer patients: from Chinese expert consensus to practice.","authors":"Yaoyao Zhu, Yujie Yan, Jiamei Fu, Qing Shao, Ying Zhang, Xiaoshuai Yuan, Jingjing Kang, Min Hu, Chenxue Jiang, Minren Hu, Ruifeng Zhao, Lan Zhao, Yaping Xu, Shuangyan Yang","doi":"10.21037/tlcr-2025-151","DOIUrl":"10.21037/tlcr-2025-151","url":null,"abstract":"<p><strong>Background: </strong>Radiation pneumonitis (RP) is a common but severe complication in lung cancer patients undergoing thoracic radiotherapy, significantly impacting patient survival and quality of life. Currently, standardized clinical protocols for predicting, preventing, and managing RP remain insufficiently applied, and the clinical effectiveness of consensus-driven management guidelines in reducing RP remains unclear. This study aimed to clarify whether implementing the Chinese expert consensus on RP could effectively decrease the incidence and severity of RP, and identify independent clinical risk factors.</p><p><strong>Methods: </strong>This retrospective comparative study included 616 lung cancer patients who underwent thoracic radiation therapy at Shanghai Pulmonary Hospital between August 2020 and January 2022. Patients were divided into two groups based on treatment periods relative to the implementation of consensus recommendations in August 2021: the pre-consensus group (treated from August 2020 to July 2021) and the post-consensus group (treated from August to January 2022). The consensus-driven interventions included three key strategies: strict limitation of planning target volume (PTV) margins, individualized lung dose constraints, and standardized steroid treatment protocols. RP incidence and severity were assessed over a 12-month follow-up according to the Common Terminology Criteria for Adverse Events (CTCAE, v5.0). Multivariate logistic regression was conducted to identify predictors for severe RP (SRP, grade ≥3).</p><p><strong>Results: </strong>The clinical characteristics were comparable between the pre- and post-consensus groups. After implementing consensus recommendations, the overall incidence of RP decreased significantly (67.3% <i>vs.</i> 55.2%, P=0.003), and grade ≥3 RP markedly reduced (9.9% <i>vs.</i> 3.4%, P=0.005). Multivariate logistic regression analysis identified independent predictors for grade ≥3 RP: pre-existing interstitial lung disease (ILD), forced expiratory volume in 1 second (FEV1), diffusing capacity for carbon monoxide (DLCO), lymphocyte baseline counts, limited PTV margin, standardized steroids use, radiotherapy dose and V20.</p><p><strong>Conclusions: </strong>Risk factor prevention and standardized treatment could decrease the occurrence of SRP. Clinicians should implement the recommendations in the RP management consensus in clinical practice. Special attention should be given to patients with identifiable risk factors such as pre-existing ILD, compromised lung function, high radiotherapy dose and low lymphocyte baseline counts, to improve patient prognosis and treatment safety.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2747-2759"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837895","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":"Assessing the prognosis of metastatic or recurrent non-small cell lung cancer in the era of modern systemic therapies: a multivariable analysis of 343 patients treated in Poland.","authors":"Rafal Suwinski, Marzena Kysiak, Bożena Cybulska-Stopa, Monika Giglok, Iwona Dębosz-Suwinska, Adam Idasiak, Seweryn Gałecki, Agata Wilk, Andrzej Świerniak","doi":"10.21037/tlcr-2025-299","DOIUrl":"10.21037/tlcr-2025-299","url":null,"abstract":"<p><strong>Background: </strong>Prognostic factor assessment in metastatic or recurrent non-small cell lung cancer (NSCLC) is based primarily on older studies from the chemotherapy era or modern trials evaluating the safety and efficacy of specific treatment regimens. However, studies that compare prognostic factors across immunotherapy, molecularly guided therapy, and chemotherapy within the same real-world context remain scarce. This gap is addressed by the present study which aims to retrospectively evaluate prognostic factors for overall survival in patients treated with diverse systemic therapies.</p><p><strong>Methods: </strong>The analysis included 343 patients with metastatic or recurrent NSCLC treated between 2006 and 2022. Treatment consisted of immune checkpoint inhibitors (ICI) in 176 patients, epidermal growth factor receptor (EGFR) inhibitors in 72, ALK/ROS inhibitors in 25 and chemotherapy in 70. Adenocarcinoma was diagnosed in 210 patients, squamous-cell cancer in 110 and other types of NSCLC in 23. Several host and tumor-related variables evaluated before therapy were categorized (mainly according to their median values) and used to construct a multivariate Cox survival model. Therapies were classified (ranked) according to the effectiveness as assessed in a univariate analysis.</p><p><strong>Results: </strong>Hemoglobin concentration [hazard ratio (HR) 0.50, P<0.001], sex (HR 0.63, P=0.0009), T stage (HR 1.38, P=0.001), pathology (HR 1.43, P=0.15), performance status (HR 1.60, P=0.002), platelet count (HR 1.46, P=0.005), lymphocyte/neutrophil ratio (HR 0.69, P=0.008), and tumor volume (HR 1.45, P=0.008) significantly influenced OS in a univariable analysis. Treatment also influenced overall survival, with a median survival times of 1.57, 1.90, 0.60 and 0.80 years for ICI, anti EGFR, ALK/ROS and chemotherapy, respectively. Multivariable analysis revealed a significant and independent influence of T stage, hemoglobin concentration, performance status, lymphocyte/neutrophil ratio, and treatment on survival. Treatment, while significant, appeared as a relatively weak independent prognosticator of survival, compared to the other variables. For sensitivity assessment, several options of the basic analysis were performed without altering, however, the qualitative outcomes of the basic analysis.</p><p><strong>Conclusions: </strong>The outcome of this study strongly encourages the routine use of readily available independent prognostic factors for survival such as T stage, hemoglobin concentration, patient performance status, and lymphocyte/neutrophil ratio, regardless of systemic treatment selected for therapy of patients with metastatic or recurrent NSCLC.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2688-2699"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837845","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":"Single-cell and spatial transcriptomics profile the interaction of <i>SPP1⁺</i> macrophages and <i>FAP⁺</i> fibroblasts in non-small cell lung cancer.","authors":"Minqin Xiao, Yiqi Deng, Hang Guo, Zhixiang Ren, Yajiao He, Xia Ren, Li-Bin Huang, Wei-Han Zhang, Hai-Ning Chen, Yang Shu, Fanxin Zeng, Yan Zhang, Heng Xu, Lanlan Wang","doi":"10.21037/tlcr-2025-244","DOIUrl":"10.21037/tlcr-2025-244","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) remains one of the most prevalent malignancies. A series of differentially expressed genes (DEGs) have been identified in tumor samples and play critical roles in modulating the characteristics of tumor cells. However, some DEGs are specifically expressed in the tumor microenvironment (TME) cells. The underlying mechanisms of the functional DEGs warrant comprehensive investigation to elucidate their contributions to tumor biology of NSCLC. Therefore, the primary goal of our study is to systematically investigate TME-related DEGs using NSCLC as a model.</p><p><strong>Methods: </strong>DEG analysis was performed by comparing bulk transcriptomes of adjacent and tumor samples across 7 independent NSCLC cohorts. Expression pattern of these DEGs were annotated to specific cell types using a single-cell RNA sequencing (scRNA-seq) dataset from 13 NSCLC studies. Myeloid and stromal cells were re-clustered to achieve a detailed characterization of cell-cell interactions within the TME. Spatial co-localization of distinct subpopulations was validated by immunofluorescence staining and spatial transcriptomics (ST). Finally, functional relevance of these interactions was evaluated using a conditional knockout mouse model.</p><p><strong>Results: </strong>A total of 82 overlapping DEGs were screened out using bulk transcriptomes across 7 NSCLC cohorts. After clustering the integrated 547,360 cells from 217 adjacent/tumor NSCLC samples with available scRNA-seq data, we observed that most of these DEGs were specifically expressed in epithelial, myeloid, and stromal cells. Notably, <i>SPP1</i> ranks the top DEG and is specifically expressed in myeloid cells. The elevated <i>SPP1</i> expression in bulk transcriptome was attributed to both enriched proportion of <i>SPP1</i> ⁺ macrophages and increased expression level of <i>SPP1</i> in such myeloid subcluster in NSCLC tumor, which was potentially regulated by several transcriptional factors (e.g., <i>HIF1A</i>, <i>ATF5</i>, and <i>STAT1</i>). Cell-cell communication analysis indicated <i>FAP</i> ⁺ fibroblasts exhibited the strongest interaction with <i>SPP1</i> ⁺ macrophages within TME. Multiple fluorescent staining demonstrated significantly increased <i>SPP1</i> ⁺ macrophage and <i>FAP</i> ⁺ fibroblast interactions in tumor compared to adjacent tissues. Nichnet analysis showed <i>VCAN-ITGB1</i> ligand-receptor axis mediating this cellular interaction. ST analysis revealed that this interaction established an immune-excluding barrier surrounding the tumor core. In addition, immune cells (CD4⁺/CD8⁺ T and NK cell) were recruited to tumor edge. Consistently, macrophage-specific <i>Spp1</i> knockout in a mouse model resulted in increased CD3⁺ and CD8⁺ T cell infiltration and reduced subcutaneous tumor size. Clinically, patients with <i>FAP</i> <sup>High</s","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2646-2669"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837898","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":"A case report and literature review of a pathologic complete response to alectinib in <i>ALK</i>-positive stage IV non-small cell lung cancer.","authors":"Mélanie Janson, Hubert Curcio, Jean-Philippe Le Rochais, Gaëtane Planchard, Pierre Demontrond, Radj Gervais","doi":"10.21037/tlcr-2025-254","DOIUrl":"10.21037/tlcr-2025-254","url":null,"abstract":"<p><strong>Background: </strong>Stage IV non-small cell lung cancer is not a curative stage. However, a novel approach to local treatment of the primary tumor may improve progression-free survival. The choice between radiotherapy or surgery, as well as the optimal timing for these treatments remains to be determined. We report here the first case, to our knowledge, of a multi-metastatic patient treated with consolidative surgery after neoadjuvant alectinib, resulting in a complete pathological response.</p><p><strong>Case description: </strong>The patient was, as is typically observed in populations with oncogenic alterations such as anaplastic lymphoma kinase (<i>ALK</i>) rearrangements, a young and non-smoker; however, he was male. Bronchial endoscopy confirmed the diagnosis of bronchopulmonary adenocarcinoma with strong <i>ALK</i> expression demonstrated by immunohistochemistry. We initiated alectinib as first-line treatment for metastatic disease; however, due to the induced oligo-metastatic disease, a local treatment of the primary tumor was discussed during multidisciplinary board. Lobectomy was performed and histological examination confirmed the complete pathological response. Adjuvant alectinib was continued for unspecified duration due to the lack of available data.</p><p><strong>Conclusions: </strong>This case suggests that local treatment, even in patients with stage IV disease, performed at the time of the best response to systemic therapy, may offer an improvement in progression free survival and perhaps a glimpse of a cure.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2869-2874"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837839","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":"Comparative efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) monotherapy versus combined EGFR-TKI and chemotherapy in resectable EGFR-mutant non-small cell lung cancer: a real-world multicenter retrospective study.","authors":"Mengying Fan, Zerui Zhao, Wanpu Yan, Hao Fu, Shijie Huang, Minglei Zhuo, Rong Yu, Xin Yang, Liping Qi, Zhen Liang, Hongchao Xiong, Jinbiao Xie, Hao Long, Ke-Neng Chen","doi":"10.21037/tlcr-2025-283","DOIUrl":"10.21037/tlcr-2025-283","url":null,"abstract":"<p><strong>Background: </strong>While perioperative immunotherapy and adjuvant targeted therapy have improved outcomes for advanced non-small cell lung cancer (NSCLC), evidence on preoperative targeted strategies remains limited. This study retrospectively evaluated the efficacy and safety of neoadjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy with or without chemotherapy in resectable EGFR-mutant NSCLC.</p><p><strong>Methods: </strong>Consecutive patients with EGFR-mutant NSCLC undergoing preoperative EGFR-TKI monotherapy or EGFR-TKI plus platinum-based chemotherapy followed by surgical resection were identified from three Chinese thoracic surgery prospectively maintained databases (2010-2023) from Peking University Cancer Hospital, Sun Yat-sen University Cancer Center, and The Affiliated Hospital of Putian University. Primary endpoints included major pathological response (MPR: ≤10% viable tumor) and pathological complete response (pCR). Safety, recurrence-free survival (RFS), and perioperative outcomes were secondary endpoints.</p><p><strong>Results: </strong>A total of 50 eligible patients were identified, including 29 females (58%) and 21 males (42%). The age range was 38 to 75 years, with an average age of 60 years. Among them, 22 patients (44%) were staged as cII, and 28 patients (56%) were staged as cIII. The EGFR mutations were found in 25 patients (50%) with exon 19 deletions, 21 patients (42%) with exon 21 L858R mutations, and 4 patients (8%) with other mutation types. Sixteen patients (32%) received first-generation TKIs, and 31 patients (62%) received third- generation TKIs. Chemotherapy mainly consisted of pemetrexed combined with carboplatin in 90% of cases. During neoadjuvant therapy, 6% of patients experienced grade 3 or higher adverse events (AEs), all in the combination therapy group. The overall objective response rate (ORR) was 64% (32/50), and 30 patients (60%) experienced a downstage in disease after treatment. The R0 resection rate was 96% (48/50), and 90% underwent video-assisted thoracoscopic surgery (VATS). Seven patients (14%) achieved pCR, and 18 patients (36%) achieved MPR postoperatively. Postoperative MPR and pCR rates were 36.0% (18/50) and 14.0% (7/50), respectively, with higher pCR in the combination group (20% <i>vs</i>. 5%; P=0.22). R0 resection was achieved in 96% (48/50). The overall 3-year RFS rates were 51.3% (53.4% combination <i>vs</i>. 46.7% monotherapy; P=0.42).</p><p><strong>Conclusions: </strong>Neoadjuvant EGFR-TKI therapy combined with chemotherapy demonstrated promising pathological responses and perioperative safety, supporting its feasibility in resectable EGFR-mutant NSCLC.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 7","pages":"2700-2709"},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837847","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}