Cancer Immunology, Immunotherapy最新文献

{"title":"Efficacy of PD-1 blockade plus chemotherapy in patients with oncogenic-driven non-small-cell lung cancer.","authors":"Haowei Wang, Lei Cheng, Jian Chen, Peixin Chen, Zhuoran Tang, Qianyi Wang, Ying Ma, Chao Zhao, Xuefei Li, Tao Jiang, Fei Zhou, Xiaoxia Chen, Caicun Zhou","doi":"10.1007/s00262-024-03937-6","DOIUrl":"10.1007/s00262-024-03937-6","url":null,"abstract":"<p><strong>Background: </strong>PD-1 blockade plus chemotherapy has become the first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC) without oncogenic drivers. Oncogenic-driven advanced NSCLC showed limited response to PD-1 blockade monotherapy or chemotherapy alone. Whether NSCLC patients with oncogenic drivers could benefit from PD-1 blockade plus chemotherapy remains undetermined.</p><p><strong>Methods: </strong>Three hundred twelve NSCLC patients with at least one oncogenic driver alteration received PD-1 plus chemotherapy or each monotherapy were retrospectively identified. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared to evaluate the therapeutic outcomes differences among patients with different oncogenic drivers.</p><p><strong>Results: </strong>One hundred sixty-two patients received PD-1 blockade plus chemotherapy, 57 received PD-1 blockade monotherapy and 93 received chemotherapy alone were included. Oncogenic driver mutations including KRAS (31.4%), EGFR (28.8%), HER2 (14.7%), BRAF (10.6%), RET (7.4%), and other mutations (7.1%) were identified. Patients with oncogenic drivers who received PD-1 blockade plus chemotherapy had significantly better outcomes compared to those received PD-1 blockade or chemotherapy alone (ORR: 51% vs. 18% vs. 25%, P < 0.001; median PFS: 10.0 [95% CI: 8.9-12.6] vs. 3.7 [95% CI: 2.9-5.1] vs. 5.3 [95% CI: 4.5-6.2] months, P < 0.001; median OS: 26.0 [95% CI: 23.0-30.0] vs. 14.3 [95% CI: 9.6-19.8] vs. 16.1 [95% CI: 11.6-21.9] months, P < 0.001). The superior efficacy was consistently found in separate analyses for patients received first-line and second/third line treatments. Among individual gene alterations, patients with KRAS, EGFR, or BRAF mutations treated with PD-1 blockade plus chemotherapy achieved markedly improved PFS and OS than those received PD-1 blockade or chemotherapy alone. Multivariate Cox regression analysis revealed that PD-1 blockade plus chemotherapy was independently associated with better PFS and OS.</p><p><strong>Conclusion: </strong>PD-1 blockade plus chemotherapy demonstrated superior efficacy than PD-1 blockade monotherapy or chemotherapy alone in patients with oncogenic-driven advanced NSCLC, particularly in KRAS, EGFR and BRAF subgroups. These findings suggest that PD-1 blockade plus chemotherapy may be considered as an optional treatment option for patients without available targeted therapies.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 3","pages":"89"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074010","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":"Novel combination therapy for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma: a systematic review and network meta-analysis.","authors":"Takafumi Yanagisawa, Keiichiro Mori, Akihiro Matsukawa, Tatsushi Kawada, Satoshi Katayama, Ekaterina Laukhtina, Pawel Rajwa, Fahad Quhal, Benjamin Pradere, Wataru Fukuokaya, Kosuke Iwatani, Renate Pichler, Jeremy Yuen-Chun Teoh, Marco Moschini, Wojciech Krajewski, Jun Miki, Shahrokh F Shariat, Takahiro Kimura","doi":"10.1007/s00262-024-03910-3","DOIUrl":"10.1007/s00262-024-03910-3","url":null,"abstract":"<p><p>Recent phase 3 randomized controlled trials (RCTs) demonstrate the promising impact of immune checkpoint inhibitor (ICI)-based combination therapies on locally advanced or metastatic urothelial carcinoma (UC). However, comparative data on the efficacy and toxicity of different ICI-based combinations are lacking. This study aims to compare the efficacy of first-line ICI-based combination therapies for locally advanced or metastatic UC using phase 3 RCT data. In November 2023, three databases were searched for RCTs evaluating oncological outcomes in patients with locally advanced or metastatic UC who were treated with first-line ICI-based combination therapies. Network meta-analysis (NMA) was conducted to compare outcomes, including overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), complete response rates (CRRs), and treatment-related adverse events (TRAEs). Subgroup analyses were based on PD-L1 status and cisplatin eligibility. The NMA included five RCTs. Enfortumab vedotin (EV) + pembrolizumab ranked the highest for improving OS (100%), PFS (100%), ORR (96%), and CRR (96%), followed by nivolumab + chemotherapy. EV + pembrolizumab combination superiority held across PD-L1 status and cisplatin eligibility. In patients who are cisplatin-eligible, EV + pembrolizumab significantly improved OS (HR: 0.68, 95%CI 0.47-0.99) and PFS (HR: 0.67, 95%CI 0.49-0.92) compared to nivolumab + chemotherapy. Durvalumab + tremelimumab was the safest combination for severe TRAEs, and EV + pembrolizumab ranked second. Our analyses support EV + pembrolizumab combination as a first-line treatment for locally advanced or metastatic UC. Thus, EV + pembrolizumab may become a guideline-changing standard treatment.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 3","pages":"76"},"PeriodicalIF":4.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074021","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":"Correction: Immune checkpoint inhibitors-related thyroid dysfunction: influencing factor analysis, prediction model development, and management strategy proposal.","authors":"Xinya Li, Zaiwei Song, Yixuan Chen, Jingjing Wu, Dan Jiang, Zhen Zhang, Zeyuan Wang, Rongsheng Zhao","doi":"10.1007/s00262-025-03941-4","DOIUrl":"10.1007/s00262-025-03941-4","url":null,"abstract":"","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"74"},"PeriodicalIF":4.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064053","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":"Therapeutic effect of fully human anti-Nrp-1 antibody on non-small cell lung cancer in vivo and in vitro.","authors":"Bo Zhang, Qin Liu, Lin Li, Yingchun Ye, Xiyuan Guo, Wenfeng Xu, Ligang Chen, Xianming Mo, Siji Nian, Qing Yuan","doi":"10.1007/s00262-024-03893-1","DOIUrl":"10.1007/s00262-024-03893-1","url":null,"abstract":"<p><p>Although immune checkpoint inhibitors have changed the treatment paradigm for non-small cell lung cancer (NSCLC), not all patients benefit from them. Therefore, there is an urgent need to explore novel immune checkpoint inhibitors. Neuropilin-1 (Nrp-1) is a unique immune checkpoint capable of exerting antitumor effects through CD8⁺ T cells. It is also a T-cell memory checkpoint that regulates long-term antitumor immunity. However, its role in NSCLC remains unclear. The aim of this study was to develop a fully human anti-Nrp-1 antibody with therapeutic effects against NSCLC in vitro and in vivo. We screened and constructed of a high-affinity anti-Nrp-1 IgG antibody from a constructed high-capacity fully human single-chain fragment variable (scFv) phage library. This novel anti-Nrp-1 IgG antibody partially restored the killing function of exhausted CD8⁺ T cells in malignant pleural fluid in vitro. Co-culture of peripheral blood mononuclear cells (PBMC) with A549 and the addition of anti-Nrp1-IgG enhanced the killing of A549 target cells, leading to an increase in late-stage apoptosis of target cells. Importantly, anti-Nrp1-IgG treatment significantly reduced tumor volume in a mouse model of lung cancer with humanized immune system. These findings suggest that 53-IgG has a promising application as a potent Nrp-1-targeting agent in NSCLC immunotherapy.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"50"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920700","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":"High CD38 expression defines a mitochondrial function-adapted CD8⁺ T cell subset with implications for lung cancer immunotherapy.","authors":"Lei-Lei Lv, Jia-Wei Zhai, Jia-Juan Wu, Gui-Qin Fan, Yao-Xin Zhang, Yu Shen, Qiu-Xia Qu, Cheng Chen","doi":"10.1007/s00262-024-03881-5","DOIUrl":"10.1007/s00262-024-03881-5","url":null,"abstract":"<p><p>Despite identifying specific CD8⁺ T cell subsets associated with immunotherapy resistance, the molecular pathways driving this process remain elusive. Given the potential role of CD38 in regulating CD8⁺ T cell function, we aimed to investigate the accumulation of CD38⁺CD8⁺ T cells in lung cancer and explore its role in immunotherapy resistance. Phenotypic analysis of tumoral CD8⁺ T cells from both lung cancer patients and immunotherapy-resistant preclinical models revealed that CD38-expressing CD8⁺ T cells consist of CD38^hi and CD38^int subsets. These cells exhibited higher expression of exhaustion markers and displayed dysregulated mitochondrial bioenergetics. Notably, increased levels of CD38^hiCD8⁺ T cells in the peripheral, but not central, tumor microenvironment were associated with a favorable response to anti-PD-1 therapy in non-small-cell lung cancer and correlated with the depth of clinical regression. This was evidenced by the greater depletion of CD38^hiCD8⁺ T cells in patients with higher regional CD38^hiCD8⁺ T cell infiltration. In immune checkpoint blockade (ICB)-resistant murine lung cancer models, PD-L1 mAbs alone failed to effectively reduce CD38^hiCD8⁺ T cell levels. Notably, combination therapy with PD-L1 mAbs and EGCG selectively restricted CD38^hiCD8⁺ T cell infiltration and enhanced IFN-γ production, significantly improving survival in this carcinoma model. The restoration of immunotherapy sensitivity was linked to improved mitochondrial function in CD38^hiCD8⁺ T cells, which was validated by the established relationship between IFN-γ production and mitochondrial metabolism. Collectively, our data highlight the role of CD38-coupled mitochondrial dysfunction in promoting CD8⁺ T cell exhaustion and intrinsic resistance to ICB therapy, thereby offering a rationale for targeting CD38 to enhance the therapeutic efficacy of PD-1 blockade in lung cancer.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"49"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920497","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 immune suppressor candidates utilizing comparative transcriptional profiling in histiocytic sarcoma.","authors":"Jennifer A Lenz, Brandon Peng, Charles-Antoine Assenmacher, Austin King, Paul J Zhang, Robert G Maki, M Andres Blanco, Enrico Radaelli, Matthew J Atherton","doi":"10.1007/s00262-024-03908-x","DOIUrl":"10.1007/s00262-024-03908-x","url":null,"abstract":"<p><p>Histiocytic sarcoma (HS) is a rare yet lethal malignancy with no established standard of care therapies. A lack of pre-clinical models limits our understanding of HS pathogenesis and identification of therapeutic targets. Canine HS shares multiple clinical and genetic similarities with human HS, supporting its use as a unique translational model. Prior studies have investigated the immunogenicity of HS. Although increased tumor infiltrating lymphocyte (TIL) density is associated with favorable outcomes in canine HS, virtually all canine patients eventually succumb to progressive disease consistent with ultimate failure of anti-tumor immunity. To investigate potential regulators of the immune tumor microenvironment (TME), we undertook a comparative transcriptional approach of three long-lived cases of canine pulmonary HS with heavy T cell infiltrate and three short-lived cases of splenic HS that lacked significant T cell inflammation and compared these data to corresponding grossly normal tissues from dogs undergoing necropsy. This comparison identified PDCD1, encoding the immune checkpoint PD-1, and SPP1, encoding the secreted pro-tumorigenic protein osteopontin, as positive differentially expressed genes (DEGs) in canine HS. TXNIP, encoding the tumor suppressor TXNIP, was the most significant negative DEG. Comparative transcriptomic studies revealed conservation of enriched (including SPP1) and depleted (including TXNIP) DEGs between canine and human HS patients. Immunohistochemistry demonstrated osteopontin in the TMEs of canine and human HS. Collectively, we uncover PD-1, osteopontin, and TXNIP as putative actionable targets in HS and further establish canine HS as a preclinical platform to screen novel immunotherapeutic approaches for this deadly disease.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"61"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920452","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":"Spatial expression of fibroblast activation protein-α in clear cell renal cell carcinomas revealed by multiplex immunoprofiling analysis of the tumor microenvironment.","authors":"Gorka Larrinaga, Miriam Redrado, Ana Loizaga-Iriarte, Amparo Pérez-Fernández, Aida Santos-Martín, Javier C Angulo, José A Fernández, Alfonso Calvo, José I López","doi":"10.1007/s00262-024-03896-y","DOIUrl":"10.1007/s00262-024-03896-y","url":null,"abstract":"<p><p>Clear cell renal cell carcinoma (ccRCC) is one of the most challenging neoplasms because of its phenotypic variability and intratumoral heterogeneity. Because of its variability, ccRCC is a good test bench for the application of new technological approaches to unveiling its intricacies. Multiplex immunofluorescence (mIF) is an emerging method that enables the simultaneous and detailed assessment of tumor and stromal cell subpopulations in a single tissue section. This novel approach represents a promising step forward for analyzing the microenvironmental cell composition and distribution across the tumor and understanding its possible interactions with tumor cells. This study provides the first characterization of the spatial distribution of fibroblast activation protein-α (FAP)-expressing cancer-associated fibroblasts (FAP + CAFs) in conjunction with lymphoid (CD4 + , CD8 + , CD4 + FOXP3 + , and CD20 +) and myeloid (CD68 +) cells in tissue sections from ccRCC in their early phases of evolution (n = 88). Both the tumor center and periphery were analyzed with mIF. FAP + CAFs and tumor-infiltrating lymphocytes (TILs) were significantly concentrated at the tumor periphery. Additionally, elevated percentages of FAP + CAFs were correlated with larger tumors and synchronous metastases. Increased levels of CD68 +  and CD4 + FOXP3 +  cells (above the 75th percentile) were linked to worse cancer-specific survival (CSS) in patients with ccRCC. Furthermore, significant correlations emerged among FAP + CAFs, TILs, and CD68 +  cells, and the co-occurrence of elevated FAP + CAFs, T-cytotoxic (CD8 +), T-regulatory (CD4 + FOXP3 +) cells, and macrophages (CD68 +) at the tumor center were independently associated with worse CSS. These findings suggest that FAP + CAFs contribute to the aggressiveness of ccRCC, and their role is potentially mediated by their ability to foster an immunosuppressive environment within the renal tumor microenvironment.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"53"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920662","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":"Cytokine profile of bronchoalveolar lavage in patients with and without checkpoint inhibitor pneumonitis.","authors":"Michelle Ploch, Songzhu Zhao, Lai Wei, Joshua A Englert, Sarah P Cohen, Morgan A Inks, Alexa S Meara, Lynn A Fussner, Dwight H Owen, Kevin Ho","doi":"10.1007/s00262-024-03902-3","DOIUrl":"10.1007/s00262-024-03902-3","url":null,"abstract":"<p><strong>Background: </strong>Checkpoint inhibitor pneumonitis (CIP) that develops following immune checkpoint inhibitor (ICI) treatment can be difficult to distinguish from other common etiologies of lung inflammation in cancer patients. Here, we evaluate the bronchoalveolar lavage fluid (BAL) for potential biomarkers specific to CIP.</p><p><strong>Methods: </strong>We conducted a retrospective study of patients who underwent standard of care bronchoscopy to compare the cytokines of interest between patients with and without CIP and with and without immune-mediated pulmonary diseases. Pulmonary diagnoses were determined by the treating clinician at the time of bronchoscopy and retroactively reviewed for agreement by the study team.</p><p><strong>Results: </strong>Thirty-seven patients were included, and 24 (64.9%) had pulmonary infection, 2 (5.4%) had pulmonary edema, 6 (16.2%) had non-CIP drug-induced pneumonitis, 3 (8.1%) had CIP, 5 (13.5%) had immune-mediated ILD or autoimmune vasculitis, 4 (10.8%) had cancer progression, and 4 (10.8%) had nonimmune-mediated interstitial lung disease (ILD). IL-6 from the BAL was significantly higher in patients with CIP compared to those with cancer progression and nonimmune-mediated ILD, and IL-6 was significantly higher in patients with immune-mediated pulmonary diseases compared to cancer progression, nonimmune-mediated ILD, and infection.</p><p><strong>Conclusions: </strong>BAL IL-6 distinguished CIP from other common, important causes of pulmonary infiltrates in patients with cancer, suggesting it may give insight into the pathophysiology of CIP and has potential as a biomarker.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"46"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920299","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":"Phase 2 study of serplulimab with the bevacizumab biosimilar HLX04 in the first-line treatment of advanced hepatocellular carcinoma.","authors":"Zhenggang Ren, Guoliang Shao, Jie Shen, Li Zhang, Xu Zhu, Weijia Fang, Guoping Sun, Yuxian Bai, Jianbing Wu, Lianxin Liu, Yuan Yuan, Jingdong Zhang, Zhen Li, Ling Zhang, Tao Yin, Jincai Wu, Xiaoli Hou, Haoyu Yu, Jing Li, Qingyu Wang, Jun Zhu, Jia Fan","doi":"10.1007/s00262-024-03917-w","DOIUrl":"10.1007/s00262-024-03917-w","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to evaluate the safety and preliminary efficacy of serplulimab, a novel programmed death-1 inhibitor, with or without bevacizumab biosimilar HLX04 as first-line treatment in patients with advanced hepatocellular carcinoma.</p><p><strong>Methods: </strong>This open-label, multicenter phase 2 study (clinicaltrials.gov identifier NCT03973112) was conducted in China and consisted of four treatment groups: group A (serplulimab 3 mg/kg plus HLX04 5 mg/kg, subsequent-line), group B (serplulimab 3 mg/kg plus HLX04 10 mg/kg, subsequent-line), group C (serplulimab 3 mg/kg, subsequent-line) and group D (serplulimab 3 mg/kg plus HLX04 10 mg/kg, first-line). Group D was the only group in which participants received the study treatment in the first-line setting. The primary endpoint was safety.</p><p><strong>Results: </strong>Following previous report on groups A and B, results of group D are herein presented. As of February 7, 2023, 61 patients were enrolled and were followed up for a median of 25.5 months. Grade ≥ 3 treatment-emergent adverse events were reported by 29 (47.5%) patients. One patient died from adverse events that were considered related to study treatment. Among the patients with at least one post-baseline tumor assessment (n = 58), the objective response rate was 29.3% (95% CI: 18.1-42.7) as assessed by an independent radiological review committee (IRRC) per RECIST v1.1. IRRC-assessed median progression-free survival was 7.3 months (95% CI: 2.8-11.0), and median overall survival was 20.4 months (95% CI: 15.0-NE), respectively.</p><p><strong>Conclusion: </strong>Serplulimab combination therapy with HLX04 showed a manageable safety profile as well as preliminary efficacy in patients with advanced HCC in the first-line setting.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"69"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920621","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":"Dual efficacy of tocilizumab in managing PD-1 inhibitors-induced myocardial inflammatory injury and suppressing tumor growth with PD-1 inhibitors: a preclinical study.","authors":"Yanxin Chen, Yuxi Luo, Yunwei Liu, Daya Luo, Anwen Liu","doi":"10.1007/s00262-024-03899-9","DOIUrl":"10.1007/s00262-024-03899-9","url":null,"abstract":"<p><p>The combined use of tocilizumab (TCZ) and immune checkpoint inhibitors (ICIs) in cancer treatment is gaining attention, but preclinical studies are lacking. Our study aims to investigate the synergistic anti-tumor effect of TCZ combined with ICIs and its role in treating immune-related adverse events (irAEs). The clinical significance of high interleukin-6 (IL-6) expression in tumor patients was analyzed from the Cancer Genome Atlas (TCGA) database. The expression levels of IL-6 were compared before and during the onset of ICIs-associated myocarditis patients. ICIs-related myocardial inflammatory injury and therapeutic lung cancer models were constructed in C57BL/6 J mice using murine-derived programmed death-1 (PD-1) inhibitors alone or in combination with TCZ. Possible inflammatory mechanisms were proposed and validated. The anti-tumor effects and mechanisms of both drugs in combination were assessed. Patients with high IL-6 expression had a poor prognosis, and those with ICIs-associated myocarditis exhibited elevated IL-6 from baseline. In the PD-1 inhibitors-associated myocardial inflammatory injury mouse model, the levels of IL-6 in the blood and cardiac tissues were significantly elevated. TCZ ameliorated immune myocardial inflammatory injury by inhibiting the IL-6/janus kinase 2 (JAK2)/signal transducer and activator of the transcription 3 (STAT3) pathway. The group treated with PD-1 inhibitors combined with TCZ showed significantly slower tumor growth than that treated with PD-1 inhibitors alone. TCZ resisted tumor growth by inhibiting the IL-6-JAK2-STAT3 pathway. By targeting the IL-6-JAK2-STAT3 pathway, TCZ can alleviate PD-1 inhibitors-associated myocardial inflammatory injury mediated by M1-polarized macrophages and plays a synergistic anti-tumor role by inhibiting lung cancer cell proliferation.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"52"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920328","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}