ImmunoTargets and Therapy最新文献

{"title":"Efficacy and Safety of Different Sequences for mFOLFIRINOX (or SOXIRI) and Gemcitabine Plus Albumin-Bound Paclitaxel in Unresectable Pancreatic Cancer.","authors":"Silan Huang, Lingli Huang, Dongsheng Zhang, Qi Jiang, Fenghua Wang, Guifang Guo","doi":"10.2147/ITT.S530434","DOIUrl":"https://doi.org/10.2147/ITT.S530434","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to evaluate and compare the therapeutic efficacy and adverse effects of two sequential treatment strategies in patients with unresectable advanced pancreatic cancer (aPC), albumin-bound-paclitaxel plus gemcitabine administered follow by mFOLFIRINOX or SOXIRI (AG-F(S)FX_m) versus the reverse sequence regimen F(S)FX_m-AG.</p><p><strong>Methods: </strong>In this retrospective analysis, patients with unresectable advanced pancreatic cancer (aPC) who received either AG-F(S)FX_m or F(S)FX_m-AG were included. Key endpoints were overall survival (OS), progression-free survival (PFS), and treatment-related toxicity. Survival outcomes were assessed using Kaplan-Meier curves, and differences between groups were examined through hazard ratios (HR) and corresponding p-values.</p><p><strong>Results: </strong>A total of 107 patients were analyzed, including 49 who underwent AG-F(S)FX_m and 58 who received F(S)FX_m-AG. The median OS was 14.60 months for F(S)FX_m-AG and 12.20 months for AG-F(S)FX_m (HR: 1.04, 95% CI: 0.69-1.57, p= 0.86). Median PFS1, median PFS2 and median total PFS (tPFS) were 5.20 months versus 4.83 months (HR: 0.81, 95% CI: 0.54-1.21, p= 0.3), 4.53 months versus 5.77 months (HR: 1.15, 95% CI: 0.71-1.88, p= 0.60) and 13.80 months versus 12.80 months (HR: 0.90, 95% CI: 0.55-1.48, p= 0.67) for F(S)FX_m-AG versus AG-F(S)FX_m. Given their comparable efficacy, we further compared the safety profiles of both regimens. The toxicity profiles differed between the two sequential treatments. Leukopenia was more common with first-line AG, while gastrointestinal toxicity, fatigue, and sensory neuropathy were more frequent with first-line F(S)FX_m. Additionally, elevated aspartate aminotransferase was more often reported with second-line AG.</p><p><strong>Conclusion: </strong>Both AG-F(S)FX_m and F(S)FX_m-AG demonstrated comparable efficacy in treating aPC, with F(S)FX_m-AG showing a trend toward improved outcomes. The choice of sequential treatment should be guided by toxicity profiles and patient-specific factors. Further prospective studies are warranted to optimize treatment sequencing and personalize therapy for improved patient outcomes.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1097-1110"},"PeriodicalIF":4.4,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12499572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psoriasis Increases the Risk of ANCA Associated Vasculitis: Insights from A Propensity Score-Matched Study.","authors":"Ran Cui, Qian Wang, Zi-Jian Kang, Yu Du, Miao Chen, Yu-Hsun Wang, James Cheng-Chung Wei, Sheng-Ming Dai","doi":"10.2147/ITT.S527251","DOIUrl":"10.2147/ITT.S527251","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the risk of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAVs) among patients with psoriasis in a large population.</p><p><strong>Patients and methods: </strong>In this population-based study using the collaborative electronic health record research network, the risk of developing AAVs (ie, eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA)) was analyzed in a cohort of patients diagnosed with psoriasis between 2006 and 2024. Non-psoriasis controls were selected in a 1:1 ratio using propensity score matching. Patients who were diagnosed with AAVs before the index date were excluded. Univariate Cox proportional hazard model and subgroup analyses were used to estimate the hazard ratio (HR) with a 95% confidence interval (CI) for developing AAVs. The Kaplan-Meier method was used to plot the cumulative incidence curves. The risk of AAVs in psoriatic patients treated with biological agents was explored.</p><p><strong>Results: </strong>After matching, 436,201 patients were included in each cohort. There were 281 incident cases of AAV during follow-up in the psoriasis cohort and 122 incident cases of AAV in the non-psoriasis cohort. The risk of developing AAVs in the psoriasis cohort was significantly higher than in the non-psoriasis cohort (HRs (95% CI) for AAVs, EGPA, and GPA were 2.01 (1.63 to 2.49), 1.84 (1.11 to 3.06), and 2.11 (1.65 to 2.71), respectively. Compared with psoriasis patients who did not receive biologics, those treated with biologics showed no statistically significant increase in AAVs risk (HR 1.31, 95% CI 0.65 to 2.66).</p><p><strong>Conclusion: </strong>Patients with psoriasis have a higher risk of AAVs development. Treatment with biologic agents is not associated with an elevated risk of AAVs.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1087-1095"},"PeriodicalIF":4.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-CD24 Antibody Plus Liposomal Doxorubicin for the Management of Residual Cancers After Incomplete Radiofrequency Ablation.","authors":"Jiayun Liu, Bo Sun, Jing Li, Xiaocui Liu, Guilin Zhang, Ziqiao Lei, Chuansheng Zheng, Xuefeng Kan","doi":"10.2147/ITT.S539926","DOIUrl":"10.2147/ITT.S539926","url":null,"abstract":"<p><strong>Background: </strong>Achieving a complete radiofrequency ablation (RFA) for a solid malignant tumor of large size or at high-risk locations is challenging. A slow release of doxorubicin by liposomal doxorubicin (L-Dox) in solid tumors can selectively suppress the immune suppressive cells. In this study, the feasibility of using anti-CD24 antibody plus L-Dox was explored to inhibit residual cancers after incomplete RFA (iRFA) of hepatocellular carcinoma (HCC), with an attempt to reduce the tumor recurrences post-RFA.</p><p><strong>Methods: </strong>The expressions of CD24 protein and sialic-acid-binding lg-like lectin 10 (Siglec-10) in residual cancers after iRFA of human HCC were evaluated. The mice orthotopic HCC models were treated by (1) pseudo iRFA: the ablation electrode was only put in the live tumor but without ablation treatment; (2) iRFA: the tumors only received iRFA treatment; (3) iRFA+anti-CD24 antibody; (4) iRFA+L-Dox; (5) iRFA+anti-CD24 antibody+L-Dox. The treatment effects and the immune microenvironment of treated tumors in each group were assessed and compared.</p><p><strong>Results: </strong>The CD24 protein and Siglec-10 were highly expressed in the residual cancers (<i>p</i><0.001). The iRFA+anti-CD24 antibody+L-Dox group had the smallest tumor size and the longest survival time (<i>p</i><0.001). The anti-CD24 antibody in combination with L-Dox significantly decreased the expressions of CD24 and Siglec-10, significantly promoted the polarization of M2-like tumor-associated macrophages (TAMs) towards M1-like TAMs, significantly reduced the regulatory T cells and myeloid-derived suppressor cells, and significantly increased the infiltrations of natural killer cells and functional CD8⁺T cells into residual cancers.</p><p><strong>Conclusion: </strong>The combined therapy of anti-CD24 antibody with L-Dox could significantly improve the suppressive tumor immune microenvironment and result in a strong tumor-killing immunity in residual cancers, which significantly inhibited the residual cancers after iRFA of HCC. These findings may lead to a new strategy of enhancing the curative efficacy of RFA for large-sized HCC or HCC at high-risk locations.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1053-1071"},"PeriodicalIF":4.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting ILT4 to Improve Immunotherapy Efficacy in Solid Tumour: From Bench to Bedside.","authors":"Aiqin Gao, Shuyun Wang, Yuping Sun","doi":"10.2147/ITT.S548082","DOIUrl":"10.2147/ITT.S548082","url":null,"abstract":"<p><p>Immunotherapy, especially immune checkpoint inhibitors (ICIs), has greatly changed the paradigm of cancer treatment in the past decade. However, the efficacy of ICIs in solid tumors is still limited. Even in patients with high PD-L1 expression, the response rate is less than 40%. The immunosuppressive tumour microenvironment (TME) represents a major cause of ICI hyporesponsiveness due to its inhibition on effective T-cell trafficking and immunity. Exploring novel immunotargets and developing combination therapeutics represent promising strategies to improve tumor response to immunotherapy. Immunoglobulin-like transcript (ILT) 4 is a classical inhibitory molecule in myeloid cells. Recently, ILT4 expression was discovered in tumour cells and multiple immunocytes in the TME, functionally inducing tumour growth, metastasis, and immune escape. Our group proposed ILT4 as a novel checkpoint molecule for tumour immunotherapy in 2018. In the past 5 years, translational research on ILT4 has made remarkable advances. Here, we update recent findings on ILT4 function in the TME, summarize the translational research on the development of therapeutic ILT4 antibodies, and highlight emerging clinical trial data supporting the role of ILT4 blockade in improving immunotherapy efficacy.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1073-1085"},"PeriodicalIF":4.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostate Cancer Immunotherapy: Time to Move Beyond Checkpoint Inhibitors.","authors":"Melissa Abel, Aanika Balaji Warner, Fatima Karzai, Ravi A Madan","doi":"10.2147/ITT.S549873","DOIUrl":"10.2147/ITT.S549873","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have led the advancement of cancer immunotherapy, with remarkable efficacy in many cancers. Prior to the advent of ICIs, prostate cancer had one of the first approvals for cancer immunotherapy with sipleucel-T, an anti-cancer vaccine. Despite this early success, ICIs have since failed to improve outcomes for most patients with prostate cancer, generating a narrative that prostate cancer is resistant immunotherapeutic approaches. Novel therapies like CAR T-cells, bispecific antibody therapies, anti-cancer vaccines and cytokine therapies are now generating early evidence for how the prostate cancer tumor immune microenvironment can be manipulated beyond checkpoint inhibition. Most notably, clinical trials with bispecific T-cell engagers (BiTEs) targeting tumor antigens like STEAP-1 and KLK2 have shown clinical promise. Moving beyond ICIs may lead to new approaches to alter the prostate cancer tumor immune microenvironment and improve clinical outcomes.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1041-1052"},"PeriodicalIF":4.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Progress of Natural Killer Cells in Hashimoto's Thyroiditis.","authors":"Yanchun Wang, Zhangren Yan, Jianhang Miao, Huafa Que, Wei Shan","doi":"10.2147/ITT.S545646","DOIUrl":"10.2147/ITT.S545646","url":null,"abstract":"<p><p>Hashimoto's thyroiditis is one of the most common autoimmune diseases, characterized by lymphocytic infiltration, thyroid autoantibody production, and progressive thyroid destruction. Natural killer cells, as innate immune effectors, play a dual role in HT pathogenesis through cytotoxicity, death receptor signaling, inflammasome activation, and secretion of proinflammatory cytokines. Recent studies using single-cell RNA sequencing have revealed functional heterogeneity of NK subsets, suggesting stage-specific roles in either amplifying or regulating inflammation. Moreover, peripheral blood from HT patients shows increased expression of activating receptors such as NKG2D and NKp30, positively correlated with thyroid autoantibody titers, while abnormal activation of the NLRP3 inflammasome drives NK cell-mediated IFN-γ release and thyroid follicular cell pyroptosis. These advances highlight NK cells as both contributors to immune imbalance and potential therapeutic targets. A better understanding of NK cell-related mechanisms will provide novel insights into disease monitoring and the development of targeted interventions for HT.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1029-1040"},"PeriodicalIF":4.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Outcomes and Hepatic Toxicity of Combined Intensity Modulated Radiotherapy and PD-1 Inhibitors in Child-Pugh Class B Advanced Hepatocellular Carcinoma.","authors":"Lijun Chen, Min Liu, Shenshen Chen, Yi Wu, Shichun Guan, Jianxu Li, Shixiong Liang","doi":"10.2147/ITT.S538796","DOIUrl":"10.2147/ITT.S538796","url":null,"abstract":"<p><strong>Purpose: </strong>There is limited research data on the management of hepatocellular carcinoma (HCC) patients with Child-Pugh class B (CP-B). This study aimed to evaluate the clinical outcomes and radiation-induced hepatic toxicity (RIHT) of combined intensity modulated radiotherapy (IMRT) and programmed cell death protein 1 (PD-1) inhibitors in advanced HCC patients with CP-B.</p><p><strong>Patients and methods: </strong>This retrospective study screened 232 CP-B advanced HCC patients who had undergone IMRT, and the irradiation scopes were intrahepatic tumor lesions and/or venous tumor thrombosis. The propensity matching method (PSM) was used to reduce selection bias between the radiotherapy (RT) and RT+PD-1 groups. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints included local progression-free survival (LPFS), out-of-field progression-free survival (outPFS), objective response rate (ORR), disease control rate (DCR), and RIHT.</p><p><strong>Results: </strong>50 and 39 patients with CP-B advanced HCC were included in the RT+PD-1 and RT groups. After PSM, 39 patients from each group were matched. The median follow-up duration was 15.53 months (95% CI, 13.83-17.22). The median OS and median PFS of RT+PD-1 group were significantly prolonged than RT group (OS:14.27 months [95% CI, 10.53-not estimable] vs 7.57 months [95% CI, 6.57-10.00], HR = 0.284; 95% CI, 0.153-0.526; p < 0.001), (PFS:9.00 months [95% CI, 5.00-not estimable] vs 4.50 months [95% CI, 3.10-6.00], HR = 0.349; 95% CI, 0.188-0.648; p < 0.001). The ORR of RT+PD-1 group was improved than RT group, 43.6% (95% CI, 27.3-59.9) vs 28.2% (95% CI, 13.4-43.0) (p = 0.157). The incidence of RIHT did not differ between the groups except the RT+PD-1 group experienced increased total bilirubin (≥grade 1) more frequently (p = 0.021).</p><p><strong>Conclusion: </strong>Combined IMRT and PD-1 inhibitors improved clinical outcomes with a comparable incidence of RIHT to radiotherapy alone in advanced HCC patients with CP-B. The individual combined IMRT and PD-1 inhibitors for CP-B could be cautiously applied weighing the survival benefits and the RIHT risks.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"1015-1028"},"PeriodicalIF":4.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T Cells Dysfunction in Multiple Myeloma.","authors":"Linyu Cai, Liping Zuo, Guangqi Wang, Qun Li, Chi Ma, Jianghua Wu, Chunyan Sun, Yu Hu","doi":"10.2147/ITT.S534784","DOIUrl":"10.2147/ITT.S534784","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a kind of plasma cell hematologic malignancy. Notable advancements in patient survival have been achieved due to the clinical application of anti-CD38 monoclonal antibody, chimeric antigen receptor T cells (CAR-T) and bispecific T cell engagers (TCEs). However, the immunosuppressive microenvironment of the bone marrow hinders the effectiveness of these novel immunotherapies, consequently restricting their efficacy. Hence, it is imperative to clarify the exact mechanisms to devise strategies aimed at improving the efficacy of immunotherapy. In this review, we provide a systematic overview of recent research concerning the different T cell subtypes in the immune evasion mechanisms of MM. The review emphasizes the imbalance between the immune surveillance and the immune suppression, and highlight recent studies about unconventional T cells, the metabolic control of immune reactions, and novel therapeutic strategies aimed at addressing immune evasion mechanisms that promote the progression of MM.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"997-1014"},"PeriodicalIF":4.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Directed-Complement Activation as a Novel Immunotherapeutic Approach for HER2-Breast Cancer.","authors":"Carole Seguin-Devaux, Bianca Brandus, Jean-Marc Plesseria, Gilles Iserentant, Jean-Yves Servais, Aubin Pitiot, Georgia Kanli, Iris Behrmann, Rafaëla Schober, Jacques Zimmer, Jacques H M Cohen, Xavier Dervillez","doi":"10.2147/ITT.S517584","DOIUrl":"10.2147/ITT.S517584","url":null,"abstract":"<p><strong>Purpose: </strong>Directing selective complement activation towards tumor cells is an attractive strategy to promote their elimination. We have generated complement-activating multimeric immunotherapeutic complexes (CoMiX), stimulating either the alternative pathway (via Factor H Related protein 4 (FHR4)) or the classical pathway (via triple Fc dimers) on HER2-expressing tumor cells.</p><p><strong>Methods: </strong>We used the C-terminal α-chain multimerizing scaffold of the C4 binding protein (C4bp) to generate CoMiX-FHR4 as well as CoMiX-Fc with 2 different anti-HER2 V_HH, V_HH(T) and V_HH(P), recognizing trastuzumab- or pertuzumab-competing epitopes, respectively. The different CoMiX were compared in vitro for C3b and C5b9 depositions, complement-dependent cytotoxicity (CDC), and their ability to activate NK cells and phagocytosis by macrophages. We further explored their therapeutic efficacy on human BT474 tumor xenografts established in nude mice.</p><p><strong>Results: </strong>CoMiX-FHR4/V_HH(T) and -FHR4/V_HH(P) lead to the highest C3b and C5b9 depositions and CDC on BT474 tumor cells (p<0.0001), both individually and in combinations with their CoMiX-Fc counterparts, surpassing the low complement activating capacity of trastuzumab and pertuzumab. All CoMiX induced BT474 cell death and phagocytosis of tumor cells by macrophages while CoMiX-Fc also stimulated NK cell activation. In human BT474 xenografts sensitive to trastuzumab, CoMiX induced a massive C3b deposition 6 hours after injection. CoMiX-FHR4 reduced the tumor volume compared to controls (p< 0.05) but to a lesser extent than trastuzumab (p< 0.001) while CoMiX-V_HH(P)/Fc led to a tumor volume reduction similar to pertuzumab. Combinations of two CoMiX-FHR4 or two CoMiX-Fc were more potent, similarly to the combination of trastuzumab and pertuzumab, leading to increased NK cell infiltration in xenografts. Importantly, CoMiX-FHR4 was still active against trastuzumab-resistant xenografts, delaying tumor growth and inducing a large NK cell infiltration.</p><p><strong>Conclusion: </strong>We showed here that directed complement activation on tumor cells is an alternative to therapeutic antibodies for future combination therapies upon resistance to standard-of-care treatment.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"979-995"},"PeriodicalIF":4.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B7-H3/CD276: Novel Immune Checkpoint and Jack of All Trades.","authors":"Brigid Larkin, Daisuke Nishizaki, Hirotaka Miyashita, Suzanna Lee, Mina Nikanjam, Ramez N Eskander, Taylor J Jensen, Sarabjot Pabla, Jeffrey M Conroy, Paul DePietro, Jason K Sicklick, Razelle Kurzrock, Shumei Kato","doi":"10.2147/ITT.S534666","DOIUrl":"10.2147/ITT.S534666","url":null,"abstract":"<p><p>Immunotherapy has transformed cancer treatment and outcomes, although resistance mechanisms remain challenging, prompting exploration of additional immune targets, including B7-H3/CD276. Indeed, B7-H3/CD276's complex and contrasting functions mark it as a jack of all trades, challenging conventional classifications of immune markers. B7-H3/CD276 is a protein belonging to the B7 family of immune regulatory molecules. It participates in immune response modulation and has been implicated in both immune activation and suppression, depending on the context though its precise immune function remains incompletely defined. B7-H3/CD276 expression is observed in various cancers and inflammatory conditions. In regard to cancer, there appears to be variability in expression both between and within malignancy types. B7-H3/CD276 targeting therapies have shown promising evidence of activity, particularly in patients over-expressing the B7-H3/CD276 protein based on immunohistochemistry. Here, we detail B7-H3/CD276's proposed immunologic and metabolic roles in the pathogenesis and progression of cancer, describe its heterogeneous patterns of RNA expression in a pan-cancer cohort, and summarize early clinical trial outcomes data.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"967-977"},"PeriodicalIF":4.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}