Journal for Immunotherapy of Cancer最新文献

{"title":"Comment on \"Nivolumab adjuvant to chemo-radiation in localized muscle-invasive urothelial cancer: primary analysis of a multicenter, single-arm, phase II, investigator-initiated trial (NEXT)\".","authors":"Xin Rui, Tingting Gu, Jiaquan Zhou","doi":"10.1136/jitc-2025-012084","DOIUrl":"https://doi.org/10.1136/jitc-2025-012084","url":null,"abstract":"","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 4","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting PD-1 and CD85j can restore intratumoral CD4⁺ GzmB⁺ T-cell functions to combat MHC-II-expressing tumors.","authors":"Boyu Wang, Xu Wang, Tianlai Wang, Kelin Meng, Taiyan Yu, Yu Xi, Shaojie Hu, Hui Xiong, Rirong Qu, Zhiwei Yuan, Xue Wang, Chenxi Zeng, Wenbin Zou, Yitao Tian, Yixin Cai, Shengling Fu, Xiangning Fu, Lequn Li","doi":"10.1136/jitc-2024-010890","DOIUrl":"https://doi.org/10.1136/jitc-2024-010890","url":null,"abstract":"<p><strong>Background: </strong>A subset of CD4⁺ T cells with cytotoxic activity has been identified, and these cells exert their effects by expressing perforin and granzymes. Despite the progress made in characterizing cytotoxic CD4⁺ T cells in various diseases, the status of cytotoxic CD4⁺ T cells in non-small cell lung cancer (NSCLC) and the underlying mechanisms involved in promoting intratumoral cytotoxic CD4⁺ T-cell activation remain unclear.</p><p><strong>Methods: </strong>We used flow cytometry to examine the phenotypic and functional properties of CD4⁺GzmB⁺ T cells in the peripheral blood and tumor tissues of patients with NSCLC. Loss-of-function analyses and RNA sequencing were used to identify the underlying mechanisms involved in the effects of interleukin (IL)-15 on the restoration of CD4⁺GzmB⁺ T-cell function in vitro. A patient-derived lung cancer explant model and an animal model were used to verify the effects of immune checkpoint inhibitors on CD4⁺GzmB⁺ T-cell activation.</p><p><strong>Results: </strong>In patients with NSCLC, impaired cytolytic function of tumor-infiltrated granzyme B (GzmB)-expressing CD4⁺ T cells was restored by IL-15 through activation of the AKT-FOXO1-T-bet axis. Moreover, IL-15 stimulation increased solute carrier family 7 member 5 (SLC7A5) expression in CD4⁺GzmB⁺ T cells in an Protein Kinase B (AKT)-dependent manner, and inhibition of SLC7A5 abrogated the effect of IL-15 on CD4⁺GzmB⁺ T cells. Additionally, we showed that the immune checkpoint molecules programmed cell death-1 (PD-1) and CD85j were mutually exclusively expressed in CD4⁺GzmB⁺ T cells and that dual targeting of PD-1 and CD85j enhanced the effector function of CD4⁺GzmB⁺ T cells by activating the AKT pathway. Notably, tumor cells expressing major histocompatibility complex (MHC)-II and IL-15 determine the effectiveness of CD4⁺GzmB⁺ T-cell-mediated antitumor immunity in response to immunotherapy.</p><p><strong>Conclusions: </strong>Our study demonstrated that tumor-infiltrating CD4⁺GzmB⁺ T cells fail to eliminate tumors. Dual blockade of PD-1 and CD85j alongside IL-15 restores the effector function of CD4⁺GzmB⁺ T cells and drives CD4⁺GzmB⁺ T-cell transformation in the tumor microenvironment to combat MHC-II-expressing tumors.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 4","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted release of a bispecific fusion protein SIRPα/Siglec-10 by oncolytic adenovirus reinvigorates tumor-associated macrophages to improve therapeutic outcomes in solid tumors.","authors":"Yenan Zhang, Bohao He, Peng Zou, Mengdi Wu, Min Wei, Chuning Xu, Jie Dong, Jiwu Wei","doi":"10.1136/jitc-2024-010767","DOIUrl":"https://doi.org/10.1136/jitc-2024-010767","url":null,"abstract":"<p><strong>Background: </strong>The pleiotropic roles of tumor-associated macrophages (TAMs) render them attractive targets in antitumor drug development. CD47/SIRPα (signal regulatory protein alpha) and CD24/Siglec-10 (sialic acid-binding immunoglobulin-like lectin 10) signaling pathways have been found to suppress macrophage phagocytosis of malignant cells. Systemic blockade of CD47/SIRPα has shown severe side effects. Intratumoral delivery of a CD47 inhibitor by oncolytic viruses (OVs) may circumvent this hurdle.</p><p><strong>Methods: </strong>To identify the characteristics of recombinant adenovirus (AdV)-SIRPα/Siglec-10, we conducted CCK8 assay, quantitative PCR, western blot, competitive binding assay, in vitro cytotoxicity assay, ELISA and phagocytosis assay. We investigated the antitumor immune responses of AdV-SIRPα/Siglec-10 using flow cytometry, various tumor-bearing mouse models, humanized tumor-bearing mouse models, immune cell depletion, RNA sequencing, and in vitro T cell activation assay.</p><p><strong>Results: </strong>Here, we developed a novel AdV encoding a fusion protein composed of the extracellular domains of murine or human SIRPα and Siglec-10 (SIRPα/Siglec-10), termed AdV-mSS or AdV-huSS. The SIRPα/Siglec-10 was effectively secreted by cells infected with AdV-mSS and functioned as a dual blocker of CD47 and CD24, thereby significantly enhancing macrophage phagocytosis. In a series of tumor models, including subcutaneous and ascitic H22 hepatocellular carcinoma (HCC), subcutaneous Hepa1-6 HCC, MC38 colorectal carcinoma, and Lewis lung carcinoma, AdV-mSS treatment markedly enhanced antitumor efficacy. Mechanistically, AdV-mSS reprogrammed TAMs toward an antitumor phenotype and enhanced the expression of major histocompatibility complex (MHC)-I/II, promoting CD8+T cell proliferation and activation. Depletion of either macrophages or CD8+T cells abrogated the antitumor efficacy of AdV-mSS. Similarly, in a humanized LM3 HCC mouse model, AdV-huSS significantly inhibited tumor growth and prolonged survival.</p><p><strong>Conclusions: </strong>Dual SIRPα/Siglec-10 inhibitor delivered intratumorally by AdV not only reinvigorated the TAM-CD8+T cell axis but also potentially reduced the risk of off-target effects. Further investigation of AdV-huSS in patients with cancer is warranted in the near future.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 4","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First reported case of a spontaneous and healthy pregnancy in a woman with persistent CAR T-cells 5 years after treatment for diffuse large B-cell lymphoma.","authors":"Ethan Abraham Canty, Lori Broderick, Daniel Flaherty, Marin Xavier, Sunita D Nasta, Lina Dajani, Andrew A White","doi":"10.1136/jitc-2024-011092","DOIUrl":"https://doi.org/10.1136/jitc-2024-011092","url":null,"abstract":"<p><p>Chimeric antigen receptor T-cell (CAR T-cell) therapy has significantly advanced cancer treatments and remission rates; however, questions exist regarding the impacts on both fertility and immune effects on infants born to mothers who have undergone CAR T-cell therapy. There are no known reported cases of persistence of CAR T-cells after cancer therapy in pregnancy. Here, we present a case of a woman with relapsed refractory diffuse large B-cell lymphoma who undertook an experimental CAR T-cell therapy, had persistence of CAR T-cells 5 years after achieving remission, spontaneously became pregnant and delivered a healthy male infant. Our case provides an example of a healthy pregnancy despite the persistence of CAR T-cells and the resultant healthy newborn without evidence of immunologic or other health effects from the CAR T-cells.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 4","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-12-producing cytokine factories induce precursor exhausted T cells and elimination of primary and metastatic tumors.","authors":"Amanda Nash, Jonathon DeBonis, Danna Murungi, Bertha Castillo, Boram Kim, Fangheng Hu, Courtney Chambers, Annie Nguyen, Andrea Hernandez, Zeshi Wang, Peter D Rios, Sofia Ghani, Ira Joshi, Douglas Isa, Ningbo Zheng, Weiyi Peng, Oleg A Igoshin, Jose Oberholzer, H Courtney Hodges, Nathan Reticker-Flynn, Omid Veiseh","doi":"10.1136/jitc-2024-010685","DOIUrl":"https://doi.org/10.1136/jitc-2024-010685","url":null,"abstract":"<p><strong>Background: </strong>Curative responses to immunotherapy require the generation of robust systemic immunity with limited toxicity. Recruitment of T cell populations such as precursor exhausted T cells (Tpex) from lymphoid tissues to tumors is a hallmark of effective treatment. However, the ability to efficiently induce this recruitment is lacking in current immunotherapy approaches. Furthermore, systemic administration of immunotherapies frequently results in dose-limiting toxicities, yielding an inadequate therapeutic window for eliciting durable responses.</p><p><strong>Methods: </strong>In this investigation, we evaluated the safety and antitumor efficacy of locally administered interleukin 12 (IL-12) using a clinically translatable cytokine delivery platform (NCT05538624) to identify Tpex recruitment capabilities at tolerable cytokine doses.</p><p><strong>Results: </strong>We show IL-12 cytokine factories can effectively treat a broad spectrum of cancer types. Single-cell RNA sequencing data suggests that the antitumor efficacy seen in our studies was due to retinal pigmented epithelial cells-mIL12 treatment inducing differentiation of Tpex cells within the tumor microenvironment. When administered in combination with checkpoint therapy, IL-12 cytokine factory treatment generated systemic abscopal immunity, preventing subcutaneous tumor outgrowth in 8/9 mice with colorectal cancer and lung metastasis in mice with melanoma. Furthermore, this platform was well tolerated in a non-human primate without signs of toxicity.</p><p><strong>Conclusions: </strong>Our new immunotherapy approach provides a robust strategy for inducing Tpex recruitment and systemic immunity against a range of solid peritoneal malignancies, many incurable with current immunotherapy strategies. Notably, these features were achieved using IL-12, and by leveraging our technology, we avoided the toxicities that have prevented the translation of IL-12 to the clinic. Our findings provide a strong rationale for the clinical development of IL-12 cytokine factories.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 4","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide CRISPR/Cas9 screen reveals factors that influence the susceptibility of tumor cells to NK cell-mediated killing.","authors":"Sophie Guia, Aurore Fenis, Camille Baudesson De Chanville, Justine Galluso, Hakim Medjouel, Bertrand Escaliere, Angelika Modelska, Margaux Vienne, Noella Lopes, Amelie Pouchin, Benjamin Rossi, Laurent Gauthier, Sandrine Roulland, Eric Vivier, Emilie Narni-Mancinelli","doi":"10.1136/jitc-2024-010699","DOIUrl":"https://doi.org/10.1136/jitc-2024-010699","url":null,"abstract":"<p><strong>Background: </strong>Natural killer (NK) cells exhibit potent cytotoxic activity against various cancer cell types. Over the past five decades, numerous methodologies have been employed to elucidate the intricate molecular mechanisms underlying NK cell-mediated tumor control. While significant progress has been made in elucidating the interactions between NK cells and tumor cells, the regulatory factors governing NK cell-mediated tumor cell destruction are not yet fully understood. This includes the diverse array of tumor ligands recognized by NK cells and the mechanisms that NK cells employ to eliminate tumor cells.</p><p><strong>Methods: </strong>In this study, we employed a genome-wide CRISPR/Cas9 screening approach in conjunction with functional cytotoxicity assays to delineate the pathways modulating the susceptibility of colon adenocarcinoma HCT-116 cells to NK cell-mediated cytotoxicity.</p><p><strong>Results: </strong>Analysis of guide RNA distribution in HCT-116 cells that survived co-incubation with NK cells identified ICAM-1 as a pivotal player in the NKp44-mediated immune synapse, with NKp44 serving as an activating receptor crucial for the elimination of HCT-116 tumor cells by NK cells. Furthermore, disruption of genes involved in the apoptosis or interferon (IFN)-γ signaling pathways conferred resistance to NK cell attack. We further dissected that NK cell-derived IFN-γ promotes mitochondrial apoptosis in vitro and exerts control over B16-F10 lung metastases in vivo.</p><p><strong>Conclusion: </strong>Monitoring ICAM-1 levels on the surface of tumor cells or modulating its expression should be considered in the context of NK cell-based therapy. Furthermore, promoting FasL expression on the NK cell surface is reaffirmed as an important strategy to enhance NK cell-mediated tumor killing, offering an additional avenue for therapeutic optimization. Additionally, considering the diffusion properties of IFN-γ, our findings highlight the potential of leveraging NK cell-derived IFN-γ to enhance direct tumor cell killing and facilitate bystander effects via cytokine diffusion, warranting further investigation.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term follow-up of BCMA CAR-T cell therapy in patients with relapsed/refractory multiple myeloma.","authors":"Chunxiang Jin, Rongrong Chen, Shan Fu, Mingming Zhang, Yuanyin Teng, Tingting Yang, Fengmei Song, Jingjing Feng, Ruimin Hong, Jiazhen Cui, Simao Huang, Huijun Xu, Yanlei Zhang, Guoqing Wei, Zhen Cai, Yok-Lam Kwong, Thomas Sau Yan Chan, Alex H Chang, He Huang, Yongxian Hu","doi":"10.1136/jitc-2024-010687","DOIUrl":"10.1136/jitc-2024-010687","url":null,"abstract":"<p><strong>Background: </strong>B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T-cell immunotherapy has shown promising results in the treatment of relapsed or refractory multiple myeloma (R/RMM). This study presents the updated long-term outcomes from our center.</p><p><strong>Methods: </strong>Between July 30, 2018, and September 27, 2023, 141 patients with R/RMM who received BCMA CAR-T therapy were enrolled. Patients underwent conditioning chemotherapy with cyclophosphamide and fludarabine, followed by BCMA CAR-T cell infusion at a median dose of 2.36×10⁶ cells/kg. The study evaluated overall response rates, long-term efficacy, safety profiles, and their associations with clinical and disease characteristics.</p><p><strong>Results: </strong>At a median follow-up of 20.2 months, the safety profile of the therapy was manageable. Grade 3/4 cytokine release syndrome occurred in 36.2% of patients, with no cases of severe neurotoxicity reported. 1-month post-infusion, grade ≥3 anemia persisted in 39.6% of patients, while neutropenia (43.3%) and thrombocytopenia (52.2%) were observed. The objective response rate (ORR) among evaluable patients was 94.8%, with 50.7% achieving a complete response (CR). The 4-year progression-free survival and overall survival rates were 37.4% (95% CI, 29.1% to 48.1%) and 63.2% (95% CI, 54.8% to 72.8%), respectively, with survival curves showing gradual flattening over time. Patients with a history of autologous stem cell transplantation (ASCT) and those with extramedullary disease demonstrated significantly inferior efficacy and survival outcomes. Peak CAR-T cell expansion was positively correlated with ORR (p<0.001) and CR (p<0.001). Notably, patients with prior ASCT exhibited significantly lower CAR-T cell expansion compared with those without prior ASCT (p<0.001). Immunophenotypic analysis of infused CAR-T cells demonstrated impaired fitness in patients who received ASCT in the past year.</p><p><strong>Conclusions: </strong>BCMA CAR-T therapy in patients with R/RMM results in significant and sustained responses, with a manageable safety profile on a large scale. Prior ASCT and extramedullary disease represent adverse prognostic factors. Patients with a history of ASCT demonstrate limited peak CAR-T cell expansion.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743107","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":"Letter to the editor: transfer learning radiomic model predicts intratumoral tertiary lymphoid structures in hepatocellular carcinoma: a multicenter study.","authors":"Pei Chen, Xuewei Wu, Shuixing Zhang","doi":"10.1136/jitc-2025-012007","DOIUrl":"https://doi.org/10.1136/jitc-2025-012007","url":null,"abstract":"","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline prediction of immune checkpoint inhibitor discontinuation for immune-related adverse events.","authors":"Pooja Middha, Rohit Thummalapalli, Zoe Quandt, Karmugi Balaratnam, Eduardo Cardenas, Christina J Falcon, Princess Margaret Lung Group, Matthew A Gubens, Scott Huntsman, Khaleeq Khan, Min Li, Christine M Lovly, Devalben Patel, Luna Jia Zhan, Geoffrey Liu, Melinda C Aldrich, Adam Schoenfeld, Elad Ziv","doi":"10.1136/jitc-2024-011273","DOIUrl":"10.1136/jitc-2024-011273","url":null,"abstract":"<p><strong>Introduction: </strong>Immune checkpoint inhibitors (ICIs) can yield remarkable clinical responses in subsets of patients with solid tumors, but they also commonly cause immune-related adverse events (irAEs). The predictive features of clinically severe irAEs leading to cessation of ICIs have yet to be established. Given the similarities between irAEs and autoimmune diseases, we sought to investigate the association of a germline polygenic risk score for autoimmune disease and discontinuation of ICIs due to irAEs.</p><p><strong>Methods: </strong>The Genetics of immune-related adverse events and Response to Immunotherapy (GeRI) cohort comprises 1302 patients with non-small cell lung cancer (NSCLC) who received ICI therapy between 2009 and 2022 at four academic medical centers. We used a published polygenic risk score for autoimmune diseases (PRS_AD) in the general population and validated it in the All of Us. We then assessed the association between PRS_AD and cessation of ICI therapy due to irAEs in the GeRI cohort, using cause-specific and Fine-Gray subdistribution hazard models. To further understand the differential effects of type of therapy on the association between PRS_AD and cessation of ICI due to irAEs, we conducted a stratified analysis by type of ICI therapy.</p><p><strong>Results: </strong>Using a competing risk model, we found an association between PRS_AD and ICI cessation due to irAEs (HR per SD=1.24, p=0.004). This association was particularly strong in patients who had ICI cessation due to irAEs within 3 months of therapy initiation (HR per SD=1.40, p=0.005). Individuals in the top quintile of PRS_AD had 4.8% ICI discontinuation for irAEs by 3 months, compared with 2% discontinuation by 3 months among patients in the bottom quintile (log-rank p=0.03). In addition, among patients who received combination programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and cytotoxic T-lymphocyte associated protein 4 (CTLA4) inhibitors, ICI discontinuation for irAEs by 3 months occurred in 4 of the 13 patients (30.8%) with high PRS_AD genetic risk (top quintile) versus 3 of 21 patients (14.3%) with low PRS_AD genetic risk (bottom quintile).</p><p><strong>Conclusions: </strong>We demonstrate an association between a polygenic risk score for autoimmune disease and early ICI discontinuation for irAEs. Our results suggest that germline genetics may be used as an adjunctive tool for risk stratification around ICI clinical decision-making in solid tumor oncology.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743033","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":"SITC strategic vision: prevention, premalignant immunity, host and environmental factors.","authors":"Sasha E Stanton, Kristin G Anderson, Tullia C Bruno, Christian M Capitini, Mary L Disis, Jennifer McQuade, Laszlo Radvanyi, Claire Vanpouille-Box, Jennifer Wargo, Kelly J Baines, Megan M Y Hong, Adnan Rajeh, Raymond H Kim, Phillip Awadalla, Lauren K Hughes, Saman Maleki Vareki","doi":"10.1136/jitc-2024-010419","DOIUrl":"10.1136/jitc-2024-010419","url":null,"abstract":"<p><p>Cancer immunotherapy has improved the survival of a subset of patients by harnessing the power of the immune system to find and destroy malignant cells. The immune system also protects the host by destroying developing premalignant and malignant tumors. Advancing our knowledge of premalignant immunity and immune changes seen in lesions that develop into invasive cancer versus those that regress offers an exciting opportunity to leverage the immune system for immune prevention and immune interception of premalignancy. Understanding the immune environment of premalignant lesions and how chronic inflammation plays a central role in the evolution of premalignancy is essential for developing effective immunoprevention and immune interceptions. Factors such as host genomics and environmental factors that affect premalignant immunity and the outcome of advanced cancers are equally important in determining the response to immunotherapy. The broad use of antibiotics and factors such as obesity can disrupt a healthy gut microbiome and drive chronic inflammation that suppresses preventive immunity or the antitumor immune response required for successful immunotherapy in advanced cancers. Modifiable lifestyle factors such as diet, obesity, smoking, and stress should be considered in designing immune prevention and interception studies, as well as for patients who receive immunotherapy for advanced cancer treatment. Other factors, such as the overall immune health of patients and existing comorbidities, affect both premalignant immunity and response to immunotherapy and, therefore, should be considered in managing patients with or without cancer. The Society for Immunotherapy of Cancer previously developed an overarching manuscript regarding the challenges and opportunities that exist in cancer immunotherapy, and this manuscript serves as an in-depth follow-up regarding the topics of premalignant immunity, immune interception, and immunoprevention, and the impact of the host on responding to immunotherapy.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743115","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}