Cancer Immunology, Immunotherapy最新文献

{"title":"Clinical significance of peripheral T-cell repertoire in head and neck squamous cell carcinoma treated with cetuximab and nivolumab.","authors":"Xuefeng Wang, Tingyi Li, Robbert J C Slebos, Ritu Chaudhary, Jose A Guevara-Patino, Marcelo Bonomi, Nabil F Saba, Christine H Chung","doi":"10.1007/s00262-025-03993-6","DOIUrl":"10.1007/s00262-025-03993-6","url":null,"abstract":"<p><p>Immunotherapy holds significant promise for treating head and neck squamous cell carcinoma (HNSCC), yet responses are limited to a subset of patients. This research investigates whether analyzing the peripheral T-cell receptor (TCR) repertoire could help identify patients who are more likely to benefit from a combination treatment of cetuximab and nivolumab. We report here updated correlative analysis using all samples profiled with deep immunoSEQ assay to study the peripheral TCR repertoires in peripheral blood mononuclear cells from patients enrolled in a phase I/II trial (NCT03370276). TCR repertoires were analyzed in 67 patients. Of these, 64 had available baseline data. Overall, our findings confirm that a more polyclonal peripheral TCR repertoire is associated with improved response to concurrent cetuximab and nivolumab in HNSCC. While the baseline productive Simpson clonality did not reach statistically significant differences in response groups, significant differences were observed within the HPV-negative subgroup and among patients who had received previous ICI therapy. Additionally, the TCR diversity at baseline and early follow-up was associated with overall survival. TRBV/TRBJ gene usage analysis also identified specific gene pairs associated with patient outcomes. Furthermore, our analysis indicates that the TCR clonality patterns are modulated by prior treatment exposures and tumor HPV status, suggesting a cohort expansion within these subgroups for further validation. Together, this study demonstrates the feasibility of leveraging the peripheral T-cell repertoire profiling and clonality dynamics as predictive biomarkers for immunotherapy efficacy in HNSCC.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"142"},"PeriodicalIF":4.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582189","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":"PRMT5 highly expressed on CD16 + CD56- natural killer cells is correlated with NK cells exhaustion in colorectal cancer mesenchyme.","authors":"Zunzhen Nie, Juanjuan Chang, Zhiqin Yang, Kaixuan Zeng, Yuangang Liu, Qian Tu, Chao Wang, Qingguo Yan, Hai Shi, Ying Guo","doi":"10.1007/s00262-025-03981-w","DOIUrl":"10.1007/s00262-025-03981-w","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the relationships between changes in the phenotype of natural killer cells (NK cells) in the microenvironment of colorectal cancer (CRC) and the expression of important immune checkpoints. To assess the expression level of CD16 bright CD56 negative (CD16 + CD56-) NK cell-associated immune checkpoints, including protein arginine methyltransferase 5 (PRMT5) and T-cell immunoreceptor with Ig and ITIM domains (TIGIT), single-immunoglobulin interleukin-1-related receptor (SIGIRR), in CRC mesenchyme.</p><p><strong>Methods: </strong>A total of 194 patients who were diagnosed with CRC were screened. The percentage of NK cells and the expression levels of their surface receptors, including PRMT5, CD56, CD69, TIGIT, CD16, IFN-γ, and SIGIRR, in the tumor microenvironment (TME) of CRC were assessed. Immunohistochemical staining, multiplex immunohistochemistry, and single-cell sequencing were performed.</p><p><strong>Results: </strong>Compared with normal mesenchyme, NK cells were less in CRC mesenchyme. The percentage of CD16 + CD56- NK cells in tumor mesenchyme was significantly higher, the number of CD16 + NK cells was more, and the number of CD56 + NK cells was less in CRC mesenchyme. High expression of TIGIT and PRMT5 expression affected the progression of CRC. The expression of PRMT5 and SIGIRR expression was significantly increased in CD16 + CD56- NK cells, and both genes were identified as important morbidity factors. PRMT5 and SIGIRR may contribute to the phenotype changes of NK cells in CRC.</p><p><strong>Conclusion: </strong>The microenvironment of CRC is in an immunosuppressive state characterized mainly by high expression of TIGIT, CD16, PRMT5, and SIGIRR; low expression of CD56, IFN-γ, and CD69; significantly decreased percentage of CD56 + NK cells; and significantly increased percentage of CD16 + CD56- NK cells with weakened killing ability. PRMT5 and TIGIT may be closely related to the formation of CD16 + CD56- NK cells with weakened killing ability.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"139"},"PeriodicalIF":4.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582193","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":"Effectiveness, safety, and patterns of use of camrelizumab in advanced esophageal cancer: an individual patient data pooled analysis of 987 patients from three prospective cohort studies.","authors":"Zhihao Lu, Guoping Sun, Jiancheng Li, Jun Zhao, Zishu Wang, Dong Qian, Zhe Yang, Na Li, Junsheng Wang, Shuanghu Yuan, Yusheng Wang, Suyi Li, Zhen Yang, Fengming Ran, Yinghua Ji, Shaojin Zhu, Yanqiao Zhang, Chen Wang, Lixin Wan, Rongrong Zheng, Wenjie Deng, Fengzhuo Cheng, Lin Shen","doi":"10.1007/s00262-025-03970-z","DOIUrl":"10.1007/s00262-025-03970-z","url":null,"abstract":"<p><strong>Background and aims: </strong>This individual patient data pooled analysis aimed to evaluate the effectiveness, safety, and patterns of use of camrelizumab in a large cohort of advanced esophageal cancer (AEC) patients.</p><p><strong>Approach and results: </strong>Adult patients (≥ 18 years) who had received camrelizumab as part of AEC treatment were pooled from three independent, prospective observational cohort studies (NCT04616040, ChiCTR1900027275, and ChiCTR2000039499). The main outcomes were patterns of camrelizumab use, progression-free survival (PFS), overall survival (OS), and safety in the overall population and specific subgroups of underrepresented patients. Among 987 patients, 450 (45.6%) received camrelizumab in the first line, 398 (40.3%) in the second line, and 139 (14.1%) in the third line or later. Most (69.7%) patients received camrelizumab plus chemotherapy regardless of treatment lines. The median PFS was 9.9 (95% CI 7.4, 14.4), 6.6 (95% CI 5.1, 8.8), and 5.7 (95% CI 3.1, 9.6) months in the first line, second line, and third line or later, respectively. The corresponding median OS was 15.5 (95% CI 12.6, 18.4), 12.1 (95% CI 10.0, 14.7), and 10.9 (95% CI 8.1, 14.5) months. Patients with poor performance status (ECOG PS ≥ 2) and with camrelizumab in the second line or later, but not patients with older age (≥ 75 years), were associated with poor survival. Adverse events occurred in 721 (73.0%) patients, with no new safety signals.</p><p><strong>Conclusions: </strong>This study provides an overview of camrelizumab use in unselected AEC patients. The real-world effectiveness and safety of camrelizumab are generally consistent with those observed in pivotal trials.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"138"},"PeriodicalIF":4.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582191","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":"Microbial dysbiosis with tryptophan metabolites alteration in lower respiratory tract is associated with clinical responses to anti-PD-1 immunotherapy in advanced non-small cell lung cancer.","authors":"Xiang-Xiang Chen, Qing Ju, Dan Qiu, Ying Zhou, Yuan Wang, Xin-Xin Zhang, Jing-Geng Li, Min Wang, Ning Chang, Xiang-Rui Xu, Yi-Bo Zhang, Tong Zhao, Ke Wang, Yong Zhang, Jian Zhang","doi":"10.1007/s00262-025-03996-3","DOIUrl":"10.1007/s00262-025-03996-3","url":null,"abstract":"<p><p>Lower respiratory tract microbiome constitutes a unique immune microenvironment for advanced non-small cell lung cancer as one of dominant localized microbial components. However, there exists little knowledge on the associations between this regional microbiome and clinical responses to anti-PD-1 immunotherapy from clinical perspectives. Here, we equivalently collected bronchoalveolar lavage fluids from 56 advanced NSCLC participants treated with none (untreated, n = 28) or anti-PD-1 immunotherapy (treated, n = 28), which was further divided into responder (n = 17) and non-responder (n = 11) subgroups according to clinical responses, aiming to compare their microbial discrepancy by performing metagenomic sequencing and targeted metabolic alterations by tryptophan sequencing. Correspondingly, microbial diversities transformed significantly after receiving immunotherapeutic agents, where Gammaproteobacteria and Campylobacter enriched, but Escherichia, Streptococcus, Chlamydia, and Staphylococcus reduced at the genus level, differences of which failed to be achieved among subgroups with various clinical responses (responder or non-responder; LDA > 2, P < 0.05^*). And the relative abundance of Staphylococcus and Streptomyces was escalated in response subgroup to anti-PD-1 immunotherapy by microbial compositional analysis (as relative abundance ≥ 3%, P < 0.05^*), no significance of which was achieved among treated and untreated groups. In addition, relative abundances of bacterial tryptophan metabolites and its derivatives were also higher in the responder subgroup, distinctively being associated with divergent genera (VIP > 1, P < 0.05^*). Our study revealed predictive performance of lower respiratory tract microbiome to antitumoral immunotherapy and further suggested that anti-PD-1 immunotherapy may alter lower respiratory tract microbiome composition and interact with its tryptophan metabolites to regulate therapeutic efficacy in advanced NSCLC, performing as potential biomarkers to prognosis and interventional strategies.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"140"},"PeriodicalIF":4.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582192","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":"Clofazimine enhances anti-PD-1 immunotherapy in glioblastoma by inhibiting Wnt6 signaling and modulating the tumor immune microenvironment.","authors":"Yuze Zhao, Yuguang Song, Weiping Li, Jiangping Wu, Zhengbao Zhao, Tingli Qu, Hong Xiao, Manyuan Wang, Min Zhu, Peiming Zheng, Huili Wan, Qingkun Song, Huixia Zheng, Shuo Wang","doi":"10.1007/s00262-025-03994-5","DOIUrl":"10.1007/s00262-025-03994-5","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is an aggressive and lethal primary brain tumor with limitedtreatment options due to its resistance to conventional therapies and an immunosuppressive tumor microenvironment. In this study, we investigated whether clofazimine, an inhibitor of the Wnt/β-catenin signaling pathway, could enhance the efficacy of anti-PD-1 immunotherapy in GBM. Our in vitro and in vivo experiments demonstrated that clofazimine suppressed GBM cell proliferation, induced apoptosis, and inhibited invasion by downregulating Wnt6-mediated activation of the Wnt/β-catenin pathway and the downstream MEK/ERK signaling cascade, leading to decreased PD-L1 expression. Notably, the combination of clofazimine and anti-PD-1 therapy significantly reduced tumor growth and intracranial invasion in orthotopic GBM mouse models, resulting in extended survival. This combination therapy also reshaped the tumor immune microenvironment by increasing cytotoxic CD8⁺ T cell infiltration, reducing regulatory T cells, and promoting T cell receptor clonality and diversity, indicative of a robust anti-tumor immune response. Our findings suggest that clofazimine enhances the therapeutic effects of anti-PD-1 immunotherapy in GBM through modulation of the Wnt6/β-catenin/PD-L1 axis and reshaping the immune microenvironment. While these results are promising, further clinical studies are needed to evaluate the efficacy and safety of this combinatory approach in GBM patients.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"137"},"PeriodicalIF":4.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572152","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":"Prostaglandin F2 receptor negative regulator as a potential target for chimeric antigen receptor-T cell therapy for glioblastoma.","authors":"Hideki Kuroda, Noriyuki Kijima, Tetsuro Tachi, Shunya Ikeda, Koki Murakami, Tomoyoshi Nakagawa, Moto Yaga, Kanji Nakagawa, Reina Utsugi, Ryuichi Hirayama, Yoshiko Okita, Naoki Kagawa, Naoki Hosen, Haruhiko Kishima","doi":"10.1007/s00262-025-03979-4","DOIUrl":"10.1007/s00262-025-03979-4","url":null,"abstract":"<p><strong>Background: </strong>Chimeric antigen receptor (CAR)-T cell therapy targeting novel glioblastoma (GBM)-specific cell surface antigens is a promising approach. However, transcriptome analyses have revealed few GBM-specific target antigens.</p><p><strong>Methods: </strong>A library of monoclonal antibodies (mAbs) against tumor cell lines derived from patients with GBM was generated. mAbs reacting with tumor cells in resected tissues from patients with GBM but not with nonmalignant human brain cells were detected. The antigens that were recognized were identified through expression cloning. CAR-T cells derived from a candidate mAb were generated, and their functionality was tested in vitro and in vivo.</p><p><strong>Results: </strong>Approximately 3,200 clones were established. Among them, 5E17 reacted with tumor cells in six of seven patients with GBM, but not with nonmalignant human brain cells. Prostaglandin F2 receptor negative regulator (PTGFRN) was identified as an antigen recognized by 5E17. CAR-T cells derived from 5E17 produced cytokines and exerted cytotoxicity upon co-culture with tumor cells from patients with GBM. Furthermore, intracranial injection of 5E17-CAR-T cells demonstrated antitumor effects in an orthotopic xenograft murine model with patient-derived GBM cells.</p><p><strong>Conclusions: </strong>Cell surface PTGFRN is a candidate target for intracranial CAR-T cell therapy for GBM. On-target off-tumor toxicity in alternative normal tissues needs to be carefully tested.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"136"},"PeriodicalIF":4.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566091","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":"LPIN3 promotes colorectal cancer growth by dampening intratumoral CD8⁺ T cell effector function.","authors":"Xiaoming Zhang, Hao Fang, Wenliang Wu, Congqing Jiang, Haizhou Wang, Yifei Shi","doi":"10.1007/s00262-025-03989-2","DOIUrl":"10.1007/s00262-025-03989-2","url":null,"abstract":"<p><p>LPIN3 has emerged as a key factor in a variety of malignancies, although its precise role in colorectal cancer (CRC) remains unclear. By analyzing the data from The Cancer Genome Atlas, we discovered that the expression pattern of LPIN3 and the relevant makeup of the immune microenvironment were immensely diverse among tumors. LPIN3 is abundantly expressed in CRC and may enhance tumor growth by activating the β-catenin signaling pathway. In addition, we discovered that LPIN3 might reduce tumor antigen presentation signals, hence suppressing CD8⁺ T cell-mediated cytotoxicity. Furthermore, high expression of LPIN3 predicts decreased CD8⁺ T cell infiltration and effector function via bioinformatics analysis. Indeed, CD8⁺ T cell-mediated cytotoxicity as well as CD8⁺ T cell infiltration and activation in vivo were strengthened by LPIN3 knockdown. To sum up, our results highlight the part that LPIN3 plays in driving the progression of CRC by regulating β-catenin signaling and CD8⁺ T cell activity.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"135"},"PeriodicalIF":5.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555866","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":"Exploring the role of TIGIT in patients with Small Cell Lung Cancer as a novel predictor of prognosis and immunotherapy response.","authors":"Li Liu, Peng Wu, Bingzhi Wang, Jiyan Dong, Chaoqi Zhang, Wenchao Liu, Jianming Ying","doi":"10.1007/s00262-025-03985-6","DOIUrl":"10.1007/s00262-025-03985-6","url":null,"abstract":"<p><strong>Background: </strong>T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is a novel immune checkpoint playing a crucial role in immunosuppression and immune evasion. This study aims to elucidate the expression patterns, characteristics, and possible mechanisms of TIGIT in small cell lung cancer (SCLC).</p><p><strong>Methods: </strong>TIGIT expression was analyzed across various cancers and normal tissues using The Cancer Genome Atlas (TCGA). Transcriptomic data from SCLC patients, sourced from the Gene Expression Omnibus (GEO) and literature, were analyzed to assess TIGIT-related characteristics. Immunohistochemistry (IHC) was used to verify TIGIT expression in post-surgical and advanced SCLC samples, focusing on expression characteristics, prognostic value, and treatment response.</p><p><strong>Results: </strong>TIGIT was significantly overexpressed in various tumors, including SCLC (p < 0.05). Higher expression was associated with better overall survival (OS) (p < 0.05). Notably, a significant positive correlation was observed between TIGIT expression and immune-related metagenes, such as HCK, interferon, and LCK (p < 0.05). Immune infiltration analysis revealed a strong positive correlation between TIGIT expression and immune score in multiple cohorts. Additionally, TIGIT expression correlated positively with immune cells, including CD8 T cells, cytotoxic lymphocytes, and B cells (p < 0.05), and multiple immune checkpoints like BTLA, ICOS, and LAG3 (p < 0.05), while it had a significant negative correlation with the TIDE score (p < 0.05). In the validation section, patients with high TIGIT expression showed significantly prolonged disease-free survival (DFS) and OS (p < 0.05), and demonstrated a better response to adjuvant chemotherapy (ACT) and immunotherapy.</p><p><strong>Conclusion: </strong>TIGIT serves as a biomarker in SCLC, with its high expression indicating favorable prognosis and treatment response. These effects may be due to TIGIT's unique immune landscape and its association with other immune checkpoints.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"134"},"PeriodicalIF":4.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540258","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":"Development of a T cell engaging bispecific antibody targeting long non-coding RNA PVT1.","authors":"Hirotaka Kato, Tomohide Tsukahara, Kenji Murata, Hiromu Nishikata, Yuka Mizue, Takashi Sasaya, Terufumi Kubo, Takayuki Kanaseki, Yoshihiko Hirohashi, Atsushi Oyagi, Tatsuo Maeda, Akihiro Miyazaki, Toshihiko Torigoe","doi":"10.1007/s00262-025-03976-7","DOIUrl":"10.1007/s00262-025-03976-7","url":null,"abstract":"<p><p>The development of effective immunotherapies for solid tumors remains a significant challenge. In previous studies, we identified PVT1, a long non-coding RNA, with the peptide HF10 derived from PVT1, presented by HLA-A24. This study aims to develop a single-chain variable fragment (scFv) that specifically recognizes the HLA-A24/HF10 complex (HF10 scFv) and to evaluate its specificity, reactivity, and therapeutic potential as part of a T cell engaging bispecific antibody (HF10xCD3) in vitro and in vivo. Using a scFv phage display library, we screened for scFv clones targeting the HLA-A24/HF10 peptide complex. The selected HF10 scFv was engineered into an IgG1 format (HF10-hIgG1), which demonstrated high affinity (K_D = 2.18 × 10⁻⁸ M) and specific detection of the HLA-A24/HF10 complex on HLA-A24( +)/PVT1( +) tumor cell lines. Furthermore, HF10 scFv was incorporated into a T cell engaging bispecific antibody (HF10xCD3), which induced cytotoxicity in these tumor cell lines. In a mouse xenograft model, HF10xCD3 administration exhibited significant anti-tumor activity. In conclusion, HF10xCD3 represents a promising candidate for immunotherapy targeting solid tumors.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"133"},"PeriodicalIF":4.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540255","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":"Identification of intratumoral microbiome-driven immune modulation and therapeutic implications in diffuse large B-cell lymphoma.","authors":"Zheng Yijia, Xiaoyu Li, Lina Ma, Siying Wang, Hong Du, Yun Wu, Jing Yu, Yunxia Xiang, Daiqin Xiong, Huiting Shan, Yubo Wang, Zhi Wang, Jianping Hao, Jie Wang","doi":"10.1007/s00262-025-03972-x","DOIUrl":"10.1007/s00262-025-03972-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, with significant clinical heterogeneity. Recent studies suggest that the intratumoral microbiome may influence the tumor microenvironment, affecting patient prognosis and therapeutic responses. This study aims to identify microbiome-related subtypes in DLBCL and assess their impact on prognosis, immune infiltration, and therapeutic sensitivity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Transcriptomic and microbiome data from 48 DLBCL patients were obtained from public databases. Consensus clustering was used to classify patients into distinct microbiome-related subtypes. Functional enrichment analysis, immune infiltration assessments, and single-cell RNA sequencing were performed to explore the biological characteristics of these subtypes. Drug sensitivity predictions were made using the OncoPredict tool. Hub genes' expression and biological function were validated and inferred in cell lines and independent cohorts of DLBCL.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Two distinct microbiome-related subtypes were identified. Patients in Cluster 1 exhibited significantly better overall survival (P &lt; 0.05), with higher immune infiltration of regulatory T cells and M0 macrophages compared to Cluster 2, which was associated with poorer outcomes. Functional enrichment analysis revealed that genes in Cluster 1 were involved in immune regulatory pathways, including cytokine-cytokine receptor interactions and chemokine signaling, suggesting enhanced anti-tumor immune responses. In contrast, genes in Cluster 2 were enriched in immunosuppressive pathways, contributing to a less favorable prognosis. Single-cell RNA sequencing analysis revealed significant heterogeneity in immune cell populations within the tumor microenvironment. B cells exhibited the most notable heterogeneity, as indicated by stemness and differentiation potential scoring. Intercellular communication analysis demonstrated that B cells played a key role in immune cell interactions, with significant differences observed in MIF signaling between B-cell subgroups. Pseudo-time analysis further revealed distinct differentiation trajectories of B cells, highlighting their potential heterogeneity across different immune environments. Metabolic pathway analysis showed significant differences in the average expression levels of metabolic pathways among B-cell subgroups, suggesting functional specialization. Furthermore, interaction analysis between core genes involved in B-cell differentiation and microbiome-driven differentially expressed genes identified nine common genes (GSTM5, LURAP1, LINC02802, MAB21L3, C2CD4D, MMEL1, TSPAN2, and CITED4), which were found to play critical roles in B-cell differentiation and were influenced by the intratumoral microbiome. DLBCL cell lines and clinical cohorts validated that MMEL1 and CITED4 with important biologically function in DLBCL cell survival and subtype c","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 4","pages":"131"},"PeriodicalIF":4.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540262","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}