Journal for Immunotherapy of Cancer最新文献

{"title":"Correction: Leveraging T cell co-stimulation for enhanced therapeutic efficacy of trispecific antibodies targeting prostate cancer.","authors":"","doi":"10.1136/jitc-2024-010140corr1","DOIUrl":"10.1136/jitc-2024-010140corr1","url":null,"abstract":"","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential regulation of calcium-NFAT signaling pathway by Akt isoforms: unraveling effector dynamics and exhaustion of cytotoxic T lymphocytes in tumor microenvironment.","authors":"Wen-Ling Chen, Yong-Lin Chang, Su-Fang Lin, Ulrike Protzer, Masanori Isogawa, Hung-Chih Yang, Li-Rung Huang","doi":"10.1136/jitc-2024-009827","DOIUrl":"10.1136/jitc-2024-009827","url":null,"abstract":"<p><strong>Background: </strong>Impairment of Akt signaling has been observed in antigen-specific cytotoxic T lymphocytes (CTLs) during chronic viral infections or tumor progression. Despite numerous studies emphasizing Akt's role in driving CTL effector functions, there is limited exploration of using Akt molecules in T-cell engineering to enhance their antiviral or antitumor capabilities for therapeutic purposes. Some studies even conclude that inhibiting Akt activation during the in vitro expansion process can prevent T-cell exhaustion and boost the antitumor effector functions of chimeric antigen receptor-T cells in vivo. Given the unique expression patterns and functions of the three Akt isoforms in immune cells, we proposed that Akt isoforms in CTLs may regulate effector functions and T-cell exhaustion distinctly.</p><p><strong>Methods: </strong>In this study, we genetically modified tumor/virus-antigen-specific T-cell receptor tg CTLs to ectopically express Akt isoforms via retroviral transduction. We subsequently conducted western blotting, flow cytometry, and RNA sequencing analysis to assess their Akt expression, expression of immune checkpoints, antitumor/antivirus functionalities, and transcriptome. Additionally, we employed a persistent Hepatitis B Virus mouse model and a syngeneic hepatocellular carcinoma mouse model for further evaluation of their antivirus/antitumor efficacies.</p><p><strong>Results: </strong>We found that both Akt1 and Akt2 overexpression enhanced the cytotoxic capabilities of mouse CTLs, although with different dynamics. Specifically, Akt2 signaling in CTLs accelerated effector functions, leading to a rapid attack on tumor cells. Conversely, Akt1 signaling triggered calcium influx and subsequent nuclear factor of activated T cells (NFAT) activation, while Akt2 signaling suppressed calcium influx, preventing excessive NFAT expression and nuclear translocation. This repression of NFAT transcriptional activity by Akt2 signaling during prolonged antigen stimulation subsequently led to reduced expression of transcription factors associated with T-cell exhaustion, such as Egr2, Nr4a, Tox, and immune checkpoints. Consequently, Akt2-overexpressed CTLs displayed reduced T-cell exhaustion within the tumor microenvironment and efficiently eradicated tumors.</p><p><strong>Conclusion: </strong>These findings highlight the essential role of Akt signaling in enabling tumor-specific CTLs to eliminate cancer cells in the solid TME, with Akt isoforms differentially regulating the calcium-calcineurin-NFAT signaling pathway. This discovery suggests the potential of AKT2 in T-cell engineering technology to enhance the survival and effector functions of adoptively transferred T cells for treating liver malignancies or chronic viral infections.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic immunomodulation by irreversible electroporation versus stereotactic ablative body radiotherapy in locally advanced pancreatic cancer: the CROSSFIRE trial.","authors":"Bart Geboers, Florentine Timmer, Danielle Vos, Hester Scheffer, Joyce Bakker, Alette Ruarus, Laurien Vroomen, Anita Stam, Sinéad Lougheed, Evelien Schouten, Robbert Puijk, Petrousjka van den Tol, Frank Lagerwaard, Jan de Vries, Anna Bruynzeel, Martijn Meijerink, Tanja de Gruijl","doi":"10.1136/jitc-2024-010222","DOIUrl":"10.1136/jitc-2024-010222","url":null,"abstract":"<p><strong>Background: </strong>Irreversible electroporation (IRE) and stereotactic ablative body radiotherapy (SABR) are cytoreductive therapies for locally advanced pancreatic cancer (LAPC). Both may signify immunogenic cell death. We aimed to compare systemic immune responses between the treatments.</p><p><strong>Methods: </strong>As part of the randomized phase II CROSSFIRE trial (NCT02791503), comparing the oncological efficacy of IRE to SABR in patients with LAPC, pre- and post-treatment (2 weeks and 3 months) peripheral blood samples were collected. Frequency and activation status of lymphocytic and myeloid subsets were determined using flow cytometry. T cell responses to pancreatic cancer associated with Wilms tumor-1 (WT-1) and survivin tumor antigens were determined by interferon-γ enzyme-linked immunospot assay.</p><p><strong>Results: </strong>In total, 20 IRE and 20 SABR-treated participants were analyzed (20 men; median age 65 (IQR 55-70)). IRE induced immediate decreases in systemic regulatory T cell (Treg) and conventional type-1 dendritic cell rates, coinciding with CD4⁺/CD8⁺ T cell activation by upregulation of PD-1, which was associated with improved overall survival (OS). SABR similarly induced immediate CD4⁺/CD8⁺ T cell activation by upregulation of Ki67 and CD25 but resulted in asynchronously delayed Treg downregulation. SABR also induced a durable increase in CD4⁺ EM T cells, associated with improved OS. Ablation-induced WT-1 or survivin-specific T cell responses were observed in 9/16 (56%) immune competent participants (IRE n=5, SABR n=4) and were associated with longer OS.</p><p><strong>Conclusion: </strong>Distinct immune stimulatory responses associated with improved OS, suggest that SABR might benefit from combined Treg depletion strategies while IRE could benefit from PD-1 checkpoint inhibition.</p><p><strong>Trial registration number: </strong>The trial was registered on clinical trials.gov (NCT02791503).</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: A new role for circulating T follicular helper cells in humoral response to anti-PD-1 therapy.","authors":"","doi":"10.1136/jitc-2020-001187corr1","DOIUrl":"10.1136/jitc-2020-001187corr1","url":null,"abstract":"","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxaliplatin, ATR inhibitor and anti-PD-1 antibody combination therapy controls colon carcinoma growth, induces local and systemic changes in the immune compartment, and protects against tumor rechallenge in mice.","authors":"Alexandra Fauvre, Chiara Ursino, Veronique Garambois, Elodie Culerier, Louis-Antoine Milazzo, Nadia Vezzio-Vié, Laura Jeanson, Candice Marchive, Augusto Faria Andrade, Eve Combes, Salima Atis, Gérald Lossaint, François Quenet, Henri-Alexandre Michaud, Lakhdar Khellaf, Ileana Corbeau, Diego Tosi, Nadine Houede, Nathalie Bonnefoy, Olivia Sgarbura, Céline Gongora, Julien Faget","doi":"10.1136/jitc-2024-010791","DOIUrl":"10.1136/jitc-2024-010791","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is the third most common cancer type and one of the leading causes of cancer-related death worldwide. The treatment of advanced metastatic CRC relies on classical chemotherapy combinations (5-fluorouracil, oxaliplatin or irinotecan). However, their use is limited by the emergence of resistance mechanisms, including to oxaliplatin. In this context, we recently showed that the combination of oxaliplatin and ataxia telangiectasia and Rad3-related protein inhibition (VE-822) is synergistic and may have a potential therapeutic effect in metastatic CRC management.</p><p><strong>Methods: </strong>In this study, we investigated the role of the VE-822+oxaliplatin (Vox) combination on the immune response and its potential synergy with an anti-programmed-cell Death receptor-1 (PD-1) antibody. We used cell lines and organoids from metastatic CRC to investigate in vitro Vox efficacy and orthotopic syngeneic mouse models of metastatic CRC to assess the efficacy of Vox+anti-PD-1 antibody and identify the involved immune cells.</p><p><strong>Results: </strong>The Vox+anti-PD-1 antibody combination completely cured tumor-bearing mice and protected them from a rechallenge. Vox was associated with a reduction of tumor-infiltrated neutrophils, CD206⁺ macrophages and regulatory T cells. Vox also induced a deep depletion of blood neutrophils. The increased bone marrow granulopoiesis failed to compensate for the Vox-mediated mature neutrophil depletion. Neutrophil depletion using a mouse recombinant anti-Ly6G antibody partially mimicked the Vox effect on the tumor microenvironment, but to a lower extent compared with the Vox+anti-PD-1 antibody combination. Vox, but not neutrophil depletion, led to the emergence of an Ly6C⁺ PD-1⁺ CD8⁺ T-cell population in the blood and spleen of tumor-harboring mice. These cells were proliferating, and expressed IFN-γ, CD62L, CXCR3 and Eomes. Moreover, the proportion of tumor antigen-specific T cells and of CD122⁺ BCL6⁺ T cells, which shared phenotypic characteristics with stem-like CD8⁺ T cells, was increased in treated mice.</p><p><strong>Conclusions: </strong>Our work strongly suggests that the Vox+anti-PD-1 antibody combination might significantly improve survival in patients with metastatic and treatment-refractory CRC by acting both on cancer cells and CD8⁺ T cells.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective activation of interleukin-2/interleukin-15 receptor signaling in tumor microenvironment using paired bispecific antibodies.","authors":"Julien Montorfani, Eric Hatterer, Laurence Chatel, Adeline Lesnier, Alizée Viandier, Bruno Daubeuf, Lise Nouveau, Pauline Malinge, Sebastien Calloud, Krzysztof Masternak, Walter Ferlin, Nicolas Fischer, Camilla Jandus, Limin Shang","doi":"10.1136/jitc-2024-010650","DOIUrl":"10.1136/jitc-2024-010650","url":null,"abstract":"<p><strong>Background: </strong>Owing to their roles in promoting T cell and natural killer (NK) cell activation and proliferation, interleukins-2 (IL-2) and interleukins-15 (IL-15) have been pursued as promising pathways to target in cancer immunotherapy. Nonetheless, their wider therapeutic application has been hampered by severe dose-limiting toxicities including systemic cytokine release and organ edema for IL-2, and inconvenient intratumoral administration for IL-15. To address these safety issues, we generated IL-2R/IL-15R×TAA (tumor-associated antigen) bispecific antibody (bsAb) pairs to selectively activate IL-2R signaling in the tumor microenvironment.</p><p><strong>Methods: </strong>Each bsAb pair is composed of one bsAb targeting CD122 and a TAA epitope, and the other bsAb targeting CD132 and the same or a different TAA epitope. In vitro assays were performed to characterize the IL-2R/IL-15R agonistic activity of the bsAb pairs, as well as their capacity to enhance T-cell-mediated killing of TAA⁺ malignant cells. Using a syngeneic mouse tumor model, in vivo biological activity and systemic toxicity of the bsAb pairs were assessed in comparison with IL-2. The in vivo antitumor activity was assessed in combination with an anti-mouse programmed cell death protein 1 (mPD-1) monoclonal antibody.</p><p><strong>Results: </strong>We demonstrated with two different TAAs (human epidermal growth factor receptor 2 (HER2) and mesothelin (MSLN)) that the CD122×TAA/CD132×TAA bsAb pairs mediate effective activation of immune cells exclusively in the presence of TAA⁺ tumor cells. In syngeneic hMSLN-MC38 tumor-bearing mice, the CD122×MSLN-1/CD132×MSLN-2 bsAb pair promotes selective activation and expansion of NK cells and central memory CD8⁺ T cells inside the tumor without inducing organ edema or systemic cytokine release, two well-known manifestations of IL-2 associated toxicity. In combination with checkpoint inhibitor anti-mPD-1, the bsAb pair boosts the accumulation of CD8⁺ effector T cells and NK cells, leading to a favorable CD8⁺ T cell to CD4⁺ regulatory T cell ratio for a more robust inhibition of tumor growth.</p><p><strong>Conclusions: </strong>Overall, the findings suggest that this innovative therapeutic approach effectively leverages the antitumor activity of IL-2 and IL-15 pathways while minimizing their associated systemic toxicities. This dual bsAb format holds potential for broader application in other immune-activating pathways.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mTOR inhibition modulates vaccine-induced immune responses to generate memory T cells in patients with solid tumors.","authors":"Henry G Withers, Junko Matsuzaki, Mark Long, Spencer R Rosario, Thinle Chodon, Takemasa Tsuji, Richard Koya, Li Yan, Jianming Wang, Tibor Keler, Shashikant B Lele, Emese Zsiros, Amit Lugade, Alan Hutson, Stephanie Blank, Nina Bhardwaj, Protul Shrikant, Song Liu, Kunle Odunsi","doi":"10.1136/jitc-2024-010408","DOIUrl":"10.1136/jitc-2024-010408","url":null,"abstract":"<p><strong>Background: </strong>Perturbation of the mechanistic target of rapamycin (mTOR) pathway can instruct effector versus memory cell fate of tumor antigen-specific T cells in preclinical models. In this study, we sought to understand the impact of rapamycin (sirolimus), an mTOR inhibitor, on reprogramming vaccine-induced T cells to enhance memory responses in patients with solid tumors following completion of their standard therapy.</p><p><strong>Methods: </strong>We conducted three phase I clinical trials employing New York esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccination approaches, with or without schedule-varied rapamycin. T cell phenotypes, functions, and Vβ usage in peripheral blood were analyzed to ask whether rapamycin influenced the generation of vaccine-induced T cells with memory attributes.</p><p><strong>Results: </strong>The addition of rapamycin to all vaccination approaches was safe and well tolerated. Immediate (days 1-14 postvaccination) or delayed (days 15-28 postvaccination) administration of rapamycin led to a significant increase in the generation of vaccine-induced NY-ESO-1-specific T cells exhibiting central memory phenotypes (CD45RO⁺CD45RA^- CCR7⁺). Moreover, delayed administration resulted in a greater than threefold (p=0.025) and eightfold (p=0.005) increase in the frequency of NY-ESO-1-specific CD4⁺ T and CD8⁺ T cells respectively at the time of long-term follow-up, compared with its immediate usage.</p><p><strong>Conclusion: </strong>Our novel finding is that delayed administration of rapamycin to patients during the contraction phase of vaccine-induced antitumor immune responses was particularly effective in increasing the frequency of memory T cells up to 1 year postvaccination in patients with solid tumors. Further studies are warranted to identify the impact of this approach on the durability of clinical remission.</p><p><strong>Trial registration number: </strong>NCT00803569, NCT01536054, NCT01522820.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FDG-PET associations with pathological response and survival with neoadjuvant immunotherapy for melanoma.","authors":"Li Zhou, Milton Jose Barros E Silva, Edward Hsiao, Zeynep Eroglu, Shahneen Sandhu, Igor Samoylenko, Serigne N Lo, Matteo S Carlino, George Au-Yeung, Maria Gonzalez, Andrew J Spillane, Thomas E Pennington, Kerwin F Shannon, Rony Kapoor, Elizabeth M Burton, Hussein A Tawbi, Rodabe N Amaria, Christian U Blank, João Pedreira Duprat, Rafaela Brito de Paula, David E Gyorki, Robyn P M Saw, Sydney Ch'Ng, Robert V Rawson, Richard A Scolyer, Ines Pires da Silva, Alexander C J van Akkooi, Georgina V Long, Alexander M Menzies","doi":"10.1136/jitc-2025-011483","DOIUrl":"10.1136/jitc-2025-011483","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant immunotherapy has become the new standard of care for stage III melanoma. This study sought to describe the metabolic changes seen with fludeoxyglucose-18-positron emission tomography (FDG-PET) following neoadjuvant immunotherapy in patients with melanoma and explore associations with pathological response and recurrence-free survival (RFS).</p><p><strong>Methods: </strong>Data from patients with macroscopic stage III nodal melanoma treated with neoadjuvant checkpoint inhibitor therapy were pooled from five melanoma centers. All patients underwent baseline and preoperative FDG-PET and CT assessments, and all had surgery. Pathological response was determined using the International Neoadjuvant Melanoma Consortium criteria, radiological response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and FDG-PET response using European Organization for Research and Treatment of Cancer (EORTC) criteria. The primary endpoint was to explore the associations of metabolic and radiological responses with pathological response; secondary endpoints were RFS outcomes stratified by each response category.</p><p><strong>Results: </strong>115 patients were included, 69% male, median age 59 years (27-92), 43% BRAF mutant, and median follow-up was 22.2 months (95% CI 13.7 to 26.4). 40 patients received anti-PD-1 monotherapy, 20 patients received pembrolizumab combined with lenvatinib, and 55 patients received ipilimumab and nivolumab. The major pathological response (MPR) rate was 62%, and the pathological complete response rate was 51%. RECIST response underestimated pathological response; patients achieving RECIST stable disease (38%) had a 50% chance of achieving MPR. The FDG-PET metabolic response rate was 73%, with most achieving an MPR (80%), especially in patients with a complete metabolic response (CMR, 96% MPR). A small proportion of patients (10%) had stable metabolic disease on FDG-PET, and all these patients were non-MPR. Patients with progressive metabolic disease were also in the majority non-MPR (79%). Patients with MPR, complete response/partial response on CT, and CMR/partial metabolic response on FDG-PET had a favorable 24-month RFS (95.6%, 97.3%, and 93.7%, respectively), with FDG-PET able to identify a greater proportion of patients with favorable progression-free survival (PFS) than pathology or CT (73%, 62%, and 43%, respectively).</p><p><strong>Conclusion: </strong>Neoadjuvant immunotherapy has high FDG-PET response rates in melanoma. FDG-PET response associates with pathological response and confers impressive RFS, suggesting this could be an important clinical tool.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell analysis of oncolytic virotherapy in adult T-cell leukemia/lymphoma.","authors":"Jianhong An, Erqiang Hu, Yang Shi, Yanan Fang, Naijia Liu, Qiang Liu, Qing Wang, Yanhua Wang, Wu He, Angelina Wang, Yinghui Song, Jidong Shan, Jinghang Zhang, Yiyu Zou, Haiying Cheng, Rafi Kabarriti, Wei Cai, Amit Verma, Roberto Alejandro Sica, Wenjun Deng, Shanye Yin","doi":"10.1136/jitc-2024-011265","DOIUrl":"10.1136/jitc-2024-011265","url":null,"abstract":"<p><p>Adult T-cell leukemia/lymphoma (ATLL), an aggressive T-cell malignancy associated with human T-cell leukemia virus type 1, presents significant therapeutic challenges due to high relapse rates and resistance to therapy. Here, we present the first reported case of ATLL treated with talimogene laherparepvec (T-VEC), an oncolytic viral immunotherapy approved for unresectable melanoma. The patient, who had experienced disease progression despite multiple lines of chemotherapy, radiotherapy, immunotherapy, and targeted therapy, underwent experimental virotherapy with two intratumoral T-VEC injections. The treatment was well-tolerated, with no significant adverse effects, and led to substantial tumor regression and clinical stabilization, suggesting potential remission. Single-cell analysis revealed that T-VEC treatment induced robust local and systemic immune responses, including tumor necrosis, activation of M1 macrophages, and infiltration of CD8+ effector memory T cells. These findings demonstrate T-VEC's safety and efficacy in generating both localized oncolysis and systemic anti-tumor immune response, highlighting its promise as a novel therapeutic approach for refractory ATLL.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-specific properties of type 1 dendritic cells in lung cancer: implications for immunotherapy.","authors":"Lucía Ines Lopez Rodriguez, Roberto Amadio, Giulia Maria Piperno, Federica Benvenuti","doi":"10.1136/jitc-2024-010547","DOIUrl":"10.1136/jitc-2024-010547","url":null,"abstract":"<p><p>Checkpoint inhibitors have led to remarkable benefits in non-small cell lung cancer (NSCLC), yet response rates remain below expectations. High-dimensional analysis and mechanistic experiments in clinical samples and relevant NSCLC models uncovered the immune composition of lung cancer tissues, providing invaluable insights into the functional properties of tumor-infiltrating T cells and myeloid cells. Among myeloid cells, type 1 conventional dendritic cells (cDC1s) stand out for their unique ability to induce effector CD8 T cells against neoantigens and coordinate antitumoral immunity. Notably, lung resident cDC1 are particularly abundant and long-lived and express a unique tissue-specific gene program, underscoring their central role in lung immunity. Here, we discuss recent insights on the induction and regulation of antitumoral T cell responses in lung cancer, separating it from the tissue-agnostic knowledge generated from heterogeneous tumor models. We focus on the most recent studies dissecting functional states and spatial distribution of lung cDC1 across tumor stages and their impact on T cell responses to neoantigens. Finally, we highlight relevant gaps and emerging strategies to harness lung cDC1 immunostimulatory potential.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}