Cancer Immunology, Immunotherapy最新文献

{"title":"Machine learning-derived prognostic signature integrating programmed cell death and mitochondrial function in renal clear cell carcinoma: identification of PIF1 as a novel target.","authors":"Guangyang Cheng, Zhaokai Zhou, Shiqi Li, Fu Peng, Shuai Yang, Chuanchuan Ren","doi":"10.1007/s00262-025-03967-8","DOIUrl":"https://doi.org/10.1007/s00262-025-03967-8","url":null,"abstract":"<p><strong>Background: </strong>The pathogenesis and progression of renal cell carcinoma (RCC) involve complex programmed cell death (PCD) processes. As the powerhouse of the cell, mitochondria can influence cell death mechanisms. However, the prognostic significance of the interplay between mitochondrial function (MF) and PCD remains unclear.</p><p><strong>Methods: </strong>We collected sets of genes related to PCD and MF. Using a powerful machine learning algorithm framework, we investigated the relationship between MF and PCD in different cohorts of patients and developed a machine learning-derived prognostic signature (mpMLDPS) related to MF and PCD. Finally, the most appropriate prognostic markers for RCC were screened by survival analysis and clinical correlation analysis, and the effects on renal cancer cells were analysed in vitro.</p><p><strong>Results: </strong>mpMLDPS was significantly correlated with the prognosis of RCC patients, and the prognosis was worse in the high mpMLDPS group, and this result was also validated in external independent cohorts. There were associations between mpMLDPS and immune checkpoints, tumour microenvironment, somatic mutations, and drug sensitivity. Finally, a novel RCC prognostic marker PIF1 was identified in model genes. The knockdown of PIF1 in vitro inhibited the progression of renal carcinoma cells.</p><p><strong>Conclusion: </strong>mpMLDPS has great potential to serve as a reliable clinical signature to improve the accuracy and reliability of prognostic assessment in RCC patients, thereby choosing the appropriate therapeutic regimen in clinical practice. PIF1 is also expected to be a novel target for the clinical treatment of RCC.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"113"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial transcriptomics reveals prognostically LYZ⁺ fibroblasts and colocalization with FN1⁺ macrophages in diffuse large B-cell lymphoma.","authors":"Liyuan Dai, Ning Lou, Liling Huang, Lin Li, Le Tang, Yuankai Shi, Xiaohong Han","doi":"10.1007/s00262-025-03968-7","DOIUrl":"https://doi.org/10.1007/s00262-025-03968-7","url":null,"abstract":"<p><strong>Background: </strong>Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous malignancy with diverse patient outcomes, largely influenced by the tumor microenvironment (TME). Understanding the roles of fibroblasts and macrophages within the TME is essential for developing personalized therapeutic strategies in DLBCL.</p><p><strong>Methods: </strong>This study is a multi-omics approach, integrating spatial transcriptomics (n = 11), bulk transcriptomics (n = 2,499), immunohistochemistry (IHC, n = 37), multiplex immunofluorescence (mIF, n = 56), and plasma samples (n = 240) to identify and characterize fibroblast and tumor-associated macrophage subtypes in the TME. Hub genes for LYZ⁺ fibroblasts and FN1⁺ macrophages were selected through univariate Cox regression and random forest analyses. Their prognostic significance was validated using IHC, mIF, and autoantibody assays in DLBCL patients treated with R-CHOP and in non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs).</p><p><strong>Results: </strong>Fibroblasts and macrophages were classified into two distinct subtypes. Patients with higher LYZ⁺ fibroblasts infiltration demonstrated superior prognosis, which was associated with increased infiltration of FN1⁺ macrophages. Key hub genes identified for LYZ⁺ fibroblasts included LYZ, ANPEP, CSF3R, C15orf48, LILRB4, CLEC7A, and COL7A1, while hub FN1⁺ macrophages genes included COL1A1, FN1, APOE, DCN, MMP2, SPP1, COL3A1, and COL1A2. Independent prognostic markers in DLBCL treated with R-CHOP and NSCLC treated with ICIs were identified, including LYZ and LILRB4 at both protein and mRNA levels, and COL1A2 autoantibodies (p < 0.05). In DLBCL patients treated with R-CHOP, FN1 mRNA and autoantibody levels were also prognostic markers (p < 0.05). In NSCLC treated with ICIs, COL3A1 autoantibody was prognostic marker (p < 0.05).</p><p><strong>Conclusions: </strong>This study identified a prognostically relevant LYZ⁺ fibroblasts and FN1⁺ macrophages in DLBCL. The hub genes associated with these subtypes represent potential biomarkers, providing insights into improving patient outcomes in DLBCL.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"123"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of frameshift-mutated TGFβR2-specific T cells in healthy subjects following administration with cancer vaccine candidate FMPV-1/GM-CSF in a phase 1 study.","authors":"Else Marit Inderberg, Nand Singh, Robert Miller, Sarah Arbe-Barnes, Henrik K Eriksen, Berit Lversen, Hedvig Vidarsdotter Juul, Jon Amund Eriksen, Karianne Risberg Handeland","doi":"10.1007/s00262-025-03969-6","DOIUrl":"https://doi.org/10.1007/s00262-025-03969-6","url":null,"abstract":"<p><p>FMPV-1 is a component of FMPV-3, an investigational cancer-specific vaccine and being developed to activate anti-cancer T cell responses targeting frameshift mutations of MSI-H cancers. FMPV-1 is designed to activate T cell responses against transforming growth factor β receptor 2 (TGFβR2) frameshift mutation. Microsatellite instability high (MSI-H) gastrointestinal cancers frequently harbour TGFβR2 frameshift mutations. This first-in-human, phase 1, single centre, open-label study included 16 healthy male subjects who received FMPV-1 (0.15 mg/injection) plus granulocyte-macrophage colony-stimulating factor (GM-CSF) (0.03 mg/injection) as two separate, co-located, injections on Days 1, 8, 15, 29 and 43. All subjects were followed to Day 365. A FMPV-1-specific delayed type hypersensitivity (DTH) skin reactivity test was performed with FMPV-1 (without GM-CSF) on Days 1, 29 and 43 with assessment after 2 days. All subjects were DTH negative at baseline, 8/16 were positive on Day 31 and 15/16 were positive on Day 45. Furthermore, the FMPV-1/GM-CSF induced frameshift mutant TGFβR2-specific T cells after the short vaccination period, and specific T cells were still detectable after 6 and 12 months indicating induction of frameshift mutant TGFβR2-specific T memory cells. Adverse events were limited to mild injection site reactions with no evidence of related systemic signs or symptoms. No other clinically important changes to vital signs, electrocardiograms, haematological, coagulation or laboratory measures related to treatment were observed. FMPV-1/GM-CSF was well tolerated and generated vaccine-specific T cell immune responses in healthy subjects. These findings support clinical studies in patients with, or at risk of, cancers carrying TGFβR2 frameshift mutations.Clinical trial identification: ClinicalTrials.gov: NCT05238558. EudraCT: 2020-004363-80.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"115"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing TAGAP to improve immunotherapy for lung squamous carcinoma treatment by targeting c-Rel in CD4+ T cells.","authors":"Peian Cai, Haibo Sun, Tongmeng Jiang, Huawei Li, Dejing Huang, Xiaopei Hao, Wei Wang, Wenqun Xing, Guanghui Liang","doi":"10.1007/s00262-025-03960-1","DOIUrl":"https://doi.org/10.1007/s00262-025-03960-1","url":null,"abstract":"<p><p>Revealing the immunosenescence, particularly in CD4+ T cell function in lung squamous carcinoma (LUSC) assists in devising individual treatment strategies. This study identifies differentially expressed genes (DEGs) between ROS1 mutated (ROS1^MUT) and wild-type (ROS1^WT) LUSC samples from the TCGA database. Using WGCNA, immune-related DEGs (IRGs) were screened. Prognostic signatures derived from IRGs were used to compare immune infiltration, chemotherapy sensitivity, and immune-phenotyping score (IPS) between high- and low-risk subgroups. Hub gene abundance in different cell clusters was analyzed via Sc-seq. TAGAP overexpression or silencing was employed to assess its impact on cytokines production and differentiation of CD4+ T cells, downstream c-Rel expression, and tumor progression. High-risk subgroups exhibited decreased infiltration of natural killer, follicular helper T, and CD8+ T cells, but increased plasma, CD4+ memory resting T, and macrophage M2 cells. These subgroups were more sensitive to Sunitinib and CTLA4 blockade. TAGAP expression was significantly reduced in LUSC. Overexpressing TAGAP enhanced CD4+ T cells to produce cytokines, promoted differentiation into Th1/Th17 cells, inhibited Treg conversion, and suppressed LUSC cell phenotype in vitro. TAGAP overexpression in CD4+ T cells also inhibited LUSC tumor growth and boosted immune infiltration in vivo. TAGAP's effects on CD4+ T cells were partly reversed by c-Rel overexpression, highlighting TAGAP's role in rejuvenating CD4+ T cells and exerting anticancer effects by inhibiting c-Rel. This study elucidates the novel therapeutic potential of targeting TAGAP to modulate CD4+ T cell activity in immunotherapy for LUSC.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"114"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing the role of regulatory b cells in cancer: development, function and treatment significance.","authors":"Ruyu Ye, Sijia Li, Yuxiao Li, Kaixin Shi, Li Li","doi":"10.1007/s00262-025-03973-w","DOIUrl":"https://doi.org/10.1007/s00262-025-03973-w","url":null,"abstract":"<p><p>B cells are essential components of the immune response, primarily recognized for their ability to produce antibodies. However, emerging research reveals their important roles in regulating immune responses and influencing tumor development, independent of antibodies. The connection between tumor progression and alterations in the tumor microenvironment is well-established, as immune infiltrating cells can enhance the survival of tumor cells by modifying their surroundings. Despite this, the majority of studies have focused on T cells and macrophages, creating a gap in our understanding of B cells. Regulatory B cells (Bregs) represent a crucial subpopulation that plays a significant role in maintaining immune balance. They may have a substantial impact on tumor immunity by negatively regulating tumor-infiltrating immune cells. This paper reviews the existing literature on Bregs, examining their development, phenotypes, functions, and the mechanisms through which they exert their regulatory effects. Furthermore, we highlight their potential interventional roles and prognostic significance in cancer therapy. By addressing the current gaps in knowledge regarding Bregs within tumors, we hope to inspire further research that could lead to innovative cancer treatments and improved outcomes for patients.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"125"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on pathological factors affecting the sensitivity of neoadjuvant therapy in hypopharyngeal cancer.","authors":"Gaofei Yin, Nuan Li, Xiaohong Chen, Yang Zhang, Zhigang Huang, Wei Guo","doi":"10.1007/s00262-025-03957-w","DOIUrl":"https://doi.org/10.1007/s00262-025-03957-w","url":null,"abstract":"<p><strong>Objective: </strong>Hypopharyngeal squamous cell carcinoma (HSCC) is a highly malignant tumor type in the head and neck region. In recent years, neoadjuvant therapy has significantly improved the laryngeal preservation rate among patients. However, there are variations in the efficacy of neoadjuvant therapy, and the identification of reliable predictive biomarkers for its efficacy remains a challenging research focus. This study aims to explore the correlation between the expression of P53, P16, and Ki67 and the response to neoadjuvant therapy.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 120 patients who underwent neoadjuvant therapy at Beijing Tongren Hospital, Capital Medical University, from January 2021 to June 2024. Patients were grouped based on their treatment response and the type of neoadjuvant therapy received. Group analysis were employed to assess the predictive value of P53, P16, and Ki67 for treatment efficacy across different neoadjuvant therapy groups.</p><p><strong>Results: </strong>A total of 120 patients were included in the study, with 60 patients each in the good response and poor response groups. The study comprised three neoadjuvant therapy groups: neoadjuvant chemotherapy, neoadjuvant targeted therapy combined with chemotherapy, and neoadjuvant immunotherapy combined with chemotherapy. Each group had 20 patients with good and poor responses, respectively. Among patients with P53 positivity, the effective rate after neoadjuvant therapy was 35.94%, significantly lower than the 66.07% observed in P53negative patients (p = 0.0017). For P16 positivity, the effective rate was 28.57%, lower than the 52.83% in P16negative patients (p = 0.0880). For patients with Ki67 < 60%, the effective rate was 33.33%, significantly lower than the 66.67% in those with Ki67 ≥ 60% (p = 0.0005). Comprehensively evaluate confirmed that P53 positivity and Ki67 < 60% were associated with poor response to neoadjuvant therapy, while P53 negativity and Ki67 ≥ 60% were associated with good response.</p><p><strong>Conclusion: </strong>Our findings suggest that the combination of P53 and P16 can be used as a preliminary tool to assess the efficacy of neoadjuvant therapy in patients with HSCC. Specifically, patients with P53 positivity and Ki67 < 60% tend to have lower sensitivity to neoadjuvant therapy. Further research may be needed to clarify the precise role of P16 in HSCC.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"118"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microsatellite instability-high status as a pan-cancer biomarker for immunotherapy efficacy.","authors":"Thierry Landre, Gaëtan Des Guetz","doi":"10.1007/s00262-025-03980-x","DOIUrl":"https://doi.org/10.1007/s00262-025-03980-x","url":null,"abstract":"<p><strong>Background: </strong>Microsatellite instability-high (MSI-H) cancers are linked to exceptional benefit from immune checkpoint inhibitors (ICIs), but studies on their efficacy across various MSI-H cancer types are limited.</p><p><strong>Methods: </strong>Randomized clinical trials (RCTs) comparing ICIs to chemotherapy in advanced MSI-H/dMMR cancers were systematically reviewed. Eligible studies included 13 RCTs with 1633 MSI-H patients across colorectal, gastric, and endometrial cancers. Data were analyzed using hazard ratios for progression-free survival (PFS) and overall survival (OS), with subgroup analyses by tumor type. Statistical heterogeneity was assessed using Cochrane's Q and I².</p><p><strong>Results: </strong>Immunotherapy significantly improved PFS and OS in MSI-H patients, with an HR for OS of 0.35 (95% CI 0.27-0.46; p < 0.00001) versus 0.81 for MSS patients. PFS showed a 64% reduced risk of progression (HR = 0.36, 95% CI 0.28-0.46; p < 0.0001). Subgroup analyses highlighted PFS benefits across tumor types: colorectal (HR = 0.28, 95% CI 0.11-0.73), gastric (HR = 0.43, 95% CI 0.27-0.68), and endometrial cancers (HR = 0.34, 95% CI 0.27-0.42).</p><p><strong>Conclusions: </strong>This meta-analysis establishes MSI-H as a predictive biomarker for ICIs, supporting its role in therapy selection and underscoring the need for MSI-H/dMMR-focused clinical trials.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"122"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CDX2 and SATB2 loss are associated with myeloid cell infiltration and poor survival in colorectal cancer.","authors":"Päivi Sirniö, Hanna Elomaa, Anne Tuomisto, Ville K Äijälä, Henna Karjalainen, Meeri Kastinen, Vilja V Tapiainen, Onni Sirkiä, Maarit Ahtiainen, Olli Helminen, Erkki-Ville Wirta, Jukka Rintala, Sanna Meriläinen, Juha Saarnio, Tero Rautio, Toni T Seppälä, Jan Böhm, Jukka-Pekka Mecklin, Markus J Mäkinen, Juha P Väyrynen","doi":"10.1007/s00262-025-03964-x","DOIUrl":"https://doi.org/10.1007/s00262-025-03964-x","url":null,"abstract":"<p><strong>Background: </strong>Caudal-type homeobox 2 (CDX2) and special AT-rich sequence-binding protein 2 (SATB2) are transcription factors playing important roles in intestinal homeostasis and participating in the regulation of intestinal inflammation. In colorectal cancer (CRC), reduced expression levels of CDX2 and SATB2 have been associated with poor differentiation and worse survival. However, their prognostic significance still needs further clarification, and the associations between CDX2 and SATB2 and immune cell infiltration into the CRC microenvironment are largely unknown.</p><p><strong>Methods: </strong>We analyzed CDX2 and SATB2 expression in two large cohorts of stages I-IV CRC patients (N = 2302) and analyzed their associations with clinicopathologic parameters, the density of local immune cells (determined with three multiplex immunohistochemistry panels and conventional immunohistochemistry), and survival.</p><p><strong>Results: </strong>In mismatch repair-proficient tumors, reduced CDX2 and SATB2 expression were associated with higher densities of immature monocytic cells, macrophages, and M2-like macrophages. Low expression of CDX2 was associated with shorter cancer-specific survival independent of conventional prognostic parameters in both cohorts. In the larger cohort, adjusted hazard ratio (HR) for negative (vs. high) CDX2 expression was 3.62 (95% CI 2.08-6.31, p_trend < 0.0001), and adjusted HR for negative (vs. high) SATB2 level was 1.61 (95% CI 0.97-2.67, p_trend= 0.002).</p><p><strong>Conclusion: </strong>This study indicates that reduced CDX2 and SATB2 expression levels are associated with myeloid cell infiltration in the CRC microenvironment and represent markers for poor outcome. These findings highlight the potential of CDX2 and SATB2 as biomarkers for classifying CRC patients and support their role in regulating the tumor microenvironment.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"111"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of neoadjuvant chemoimmunotherapy with planned surgery and concurrent chemoradiation followed by immunotherapy for potentially resectable stage III non-small-cell lung cancer: a retrospective study.","authors":"Yana Qi, Xiaoyang Zhai, Qinhao Xu, Yuqin Jin, Yingfan Guo, Miaoqing Zhao, Hui Zhu, Hongbo Guo","doi":"10.1007/s00262-025-03961-0","DOIUrl":"https://doi.org/10.1007/s00262-025-03961-0","url":null,"abstract":"<p><strong>Objective: </strong>Despite the promising potential of neoadjuvant chemoimmunotherapy for non-small cell lung cancer (NSCLC), there is limited consensus on the optimal treatment strategy for potentially resectable NSCLC. This study aimed to evaluate the efficacy and safety of neoadjuvant chemoimmunotherapy (neoCT/IO) with planned surgery versus definitive concurrent chemoradiation followed by immunotherapy (cCRT + IO) in potentially resectable stage III NSCLC.</p><p><strong>Methods: </strong>This retrospective study analyzed data from patients with potentially resectable stage III NSCLC who underwent neoCT/IO with planned surgery or cCRT + IO between March 2020 and June 2023. Propensity score matching (PSM) was used to balance heterogeneity between groups. Efficacy outcomes, safety profiles and patterns of disease recurrence were assessed.</p><p><strong>Results: </strong>A total of 308 eligible patients were included in this study, of whom 195 (63.3%) underwent neoCT/IO and 113 (36.7%) received cCRT + IO. The neoCT/IO group consisted of patients who underwent neoCT/IO + Surgery and neoCT/IO + Radiotherapy. After 1:1 PSM, each group consisted of 105 patients. The median progression-free survival (PFS) was 25.9 months in the cCRT + IO group and not reached (NR) in the neoCT/IO group (hazard ratio: 2.91, 95% confidence interval: 1.77-4.78; p < 0.001). Median overall survival (OS) was NR in either group, with 3-year OS rates of 87.5% in the neoCT/IO group and 75.0% in the cCRT + IO group (p = 0.22). The incidence of grade 3/4 treatment-related adverse events was similar in both groups, except for a higher incidence of grade 3/4 hematological toxicity in the cCRT + IO group.</p><p><strong>Conclusions: </strong>For patients with potentially resectable stage III NSCLC, neoCT/IO appears to be a safe approach and may offer better survival outcomes compared with cCRT + IO. Prospective randomized trials are needed to further validate these findings.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"119"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis and experimental validation of disulfidptosis-associated prognostic signature and immune microenvironment characterization of gastric cancer.","authors":"Huangjie Zhang, Jinguo Hu, Yuanqiang Li, Yanyang Liu, Huize Shen, Zeng Wang, Qinglin Li","doi":"10.1007/s00262-024-03883-3","DOIUrl":"https://doi.org/10.1007/s00262-024-03883-3","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is one of the most common causes of cancer-related death worldwide. As a novel form of programmed cell death, disulfidptosis is characterized by excessive cysteine accumulation, disulfide stress and actin destruction. There is evidence that targeting disulfidptosis is a promising anticancer strategy. Further improvement of GC risk stratification based on disulfidptosis has positive clinical significance.</p><p><strong>Methods: </strong>We analyzed the expression levels of disulfidptosis-associated genes (DPAGs) in normal and GC tissues and characterized the molecular subtypes of GC patients. Based on the characteristics of DPAG subtypes, differentially expressed prognosis-related genes were selected by LASSO-univariate Cox analysis and multivariate Cox analysis analyzed to establish a prognostic model. Using single-cell sequencing analysis reveals the cell subpopulation for GC. The function of the selected target in GC was verified by in vitro experimental means, including siRNA, qRT-PCR, Western blot, CCK-8, and Transwell assay.</p><p><strong>Results: </strong>DPAG score was verified to be an independent prognostic factor of GC and was significantly associated with poor prognosis of gastric cancer. Subsequent studies on subgroup immunoinfiltration characteristics, drug sensitivity analysis, immunotherapy response and somatic mutation characteristics of DPAG score comprehensively confirmed the potential guiding significance of DPAG score for individualized treatment of gastric cancer patients. Single-cell sequencing analysis revealed the expression characteristics of DPAG-related prognostic signatures across cell subpopulations. In vitro experiments showed APC11, as one of the selected DPAGs, was highly expressed in gastric cancer, and knockdown of APC11 could significantly inhibit the proliferation and migration of GC cells, demonstrating the reliability of bioinformatics results.</p><p><strong>Conclusion: </strong>The results of this study provide a new perspective for exploring the role of disulfidptosis in the occurrence and development of GC.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"116"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}