Journal of immunology最新文献_第5页

CD55hi MAIT cells with elevated cytokine secretion and activation markers serve as potential diagnostic indicators in Sjögren's disease. CD55hi MAIT细胞的细胞因子分泌和激活标志物升高可作为Sjögren病的潜在诊断指标。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-03 DOI: 10.1093/jimmun/vkaf226

Yiming Gao, Hanxi Luo, Bohao Yang, Xuzheng Song, Ziqi Xiong, Ayibaota Bahabayi, Zhonghui Zhang, Chen Liu

{"title":"CD55hi MAIT cells with elevated cytokine secretion and activation markers serve as potential diagnostic indicators in Sjögren's disease.","authors":"Yiming Gao, Hanxi Luo, Bohao Yang, Xuzheng Song, Ziqi Xiong, Ayibaota Bahabayi, Zhonghui Zhang, Chen Liu","doi":"10.1093/jimmun/vkaf226","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf226","url":null,"abstract":"Mucosal-associated invariant T (MAIT) cells play a vital role in immune responses, yet their involvement in autoimmune diseases such as Sjögren's disease (SjD) remains unclear. CD55, a key regulator of complement activation, influences immune cell function. This study investigates CD55 expression on MAIT cells in SjD patients and healthy controls, evaluating its potential as a diagnostic marker. Flow cytometry was used to assess CD55 expression on MAIT cell subsets, including CD4-CD8+, CD4+CD8-, double-positive (DP), and double-negative (DN), in peripheral blood from SjD patients and healthy controls. Functional markers (PD-1, CD83, and CD44), cytokine production (TNF-α, IFN-γ, IL-17, IL-22), and granzyme B (GZMB) secretion were analyzed following 5-OP-RU and brefeldin A stimulation. Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic utility of CD55 expression. CD55 was highly expressed on MAIT cells, with the highest expression intensity observed in DP MAIT cells, followed by CD4+CD8- MAIT and CD4-CD8+ MAIT, with the lowest expression found in DN MAIT cells. CD55hi MAIT cells demonstrated significantly higher percentages of PD-1+, CD83+, and CD44+ cells, along with enhanced cytokine and GZMB secretion following stimulation. In SjD patients, CD55 expression was significantly upregulated in MAIT cells. ROC analysis indicated that CD55hi MAIT cells have potential diagnostic value for SjD. CD55 is highly expressed on MAIT cells, with upregulation in SjD patients correlating with inflammation and autoantibodies, suggesting CD55hi MAIT cells as a potential diagnostic marker for SjD.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FLT3L neutralization reduces dendritic cell numbers, T Cell activation, and salivary gland lymphocyte infiltration in the NOD.H2h4 Sjögren's mouse model. FLT3L中和可减少NOD的树突状细胞数量、T细胞活化和唾液腺淋巴细胞浸润。H2h4 Sjögren的小鼠模型。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-03 DOI: 10.1093/jimmun/vkaf220

Agata Bartczak, Dorothy Sims, Kamelia Zerrouki, Brian Naiman, Ariful Qadri, Anna M Hansen, Annie Lau-Kilby

{"title":"FLT3L neutralization reduces dendritic cell numbers, T Cell activation, and salivary gland lymphocyte infiltration in the NOD.H2h4 Sjögren's mouse model.","authors":"Agata Bartczak, Dorothy Sims, Kamelia Zerrouki, Brian Naiman, Ariful Qadri, Anna M Hansen, Annie Lau-Kilby","doi":"10.1093/jimmun/vkaf220","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf220","url":null,"abstract":"The Feline McDonough sarcoma-like tyrosine kinase 3 (FLT3)/FLT3 ligand (FLT3L) pathway is associated with pathogenesis of several autoimmune diseases, including Sjögren's. Inflammatory signals increase FLT3L levels; FLT3L signaling promotes further inflammation through the differentiation, function, and survival of immune cells, including dendritic cells (DCs), monocytes, and B cells. Patients with Sjögren's have elevated FLT3L levels, increased infiltration of DCs, macrophages, and B cells into salivary glands and tertiary lymphoid structures (TLS). We hypothesized that therapeutically neutralizing FLT3L may reduce inflammatory manifestations in the NOD.H2h4 spontaneous Sjögren's mouse model. Female mice aged 15 to 17 wk, an age at which features of Sjögren's have developed, were administered an anti-mouse FLT3L monoclonal antibody or isotype control for 8 wk. Compared with control, anti-FLT3L antibody treatment significantly reduced free serum FLT3L, splenic DC numbers, T cell activation, and salivary gland TLS (P < 0.05 for all). Neutralizing FLT3L may effectively treat Sjögren's and other FLT3L-associated autoimmune diseases.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TGFβ limits proximal CD8+ TCR signaling via PTPN22 following strong and moderate agonism. TGFβ通过PTPN22抑制CD8+ TCR近端信号传导。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-03 DOI: 10.1093/jimmun/vkaf216

Andrew J Gunderson, Kelley Jordan, Tomoko Yamazaki, Hans-Peter Raué, Gwen Kramer, Nathaniel Fox, Mark K Slifka, Michael J Gough, Marka R Crittenden, Kristina H Young

{"title":"TGFβ limits proximal CD8+ TCR signaling via PTPN22 following strong and moderate agonism.","authors":"Andrew J Gunderson, Kelley Jordan, Tomoko Yamazaki, Hans-Peter Raué, Gwen Kramer, Nathaniel Fox, Mark K Slifka, Michael J Gough, Marka R Crittenden, Kristina H Young","doi":"10.1093/jimmun/vkaf216","DOIUrl":"10.1093/jimmun/vkaf216","url":null,"abstract":"Transforming growth factor beta (TGFβ) is an immunosuppressive cytokine that is overexpressed in tumor microenvironments. We have shown that CD8+ T cells with genetic ablation of the TGFβ type I receptor, Alk5 (CD8ΔALK5), were more sensitive to αCD3 stimulation resulting in enhanced proliferation and cytokine production. Based on these data, we hypothesized that TGFβ impaired T-cell receptor (TCR) signaling. We tested in vitro cytotoxicity of wild-type (WT) and CD8ΔALK5 OT-I T cells against murine oral carcinoma models transduced with ovalbumin altered peptide ligands (APLs) of differing affinities and found that loss of TGFβ renders CD8+ T cells more cytotoxic, but with diminishing effect at lower TCR agonism. TGFβ limits proximal TCR signaling intensity and duration, mediated by an interaction between the TGFβ type II receptor, PTPN22, and Zap70 that requires the Alk5 receptor. Downstream TCR signal integration is impaired by TGFβ following high and moderate, but not low TCR agonism. In vitro and in vivo models of chronic antigen stimulation demonstrate that TGFβ promotes both stem-like differentiation and terminal exhaustion, with loss of the more cytotoxic transitory exhausted population. Tumors of mixed APL clonality were implanted into Rag-/- animals followed by adoptive cell transfer of WT or CD8ΔALK5 OT-I T cells and monitored for clonal outgrowth. CD8ΔALK5 OT-I T cells were better able to control tumor clones with moderate TCR agonism compared to WT OT-I T cells. Targeting TGFβ signaling is one approach to enhance TCR signaling following strong or moderate agonism, alter differentiation toward more cytotoxic transitory exhaustion, and reduce terminal exhaustion, to improve antitumor immunity.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12412895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adjuvant conditioning enhances neutrophil function while inducing a suppressive peritoneal macrophage phenotype. 辅助调节增强中性粒细胞功能，同时诱导抑制腹膜巨噬细胞表型。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-02 DOI: 10.1093/jimmun/vkaf206

Thais Boccia, Victor Fattori, Matheus Deroco Veloso Da Silva, Nathan L Asquith, Weikang Pan, Michael S Rogers, Ivan Zanoni, Alex G Cuenca

{"title":"Adjuvant conditioning enhances neutrophil function while inducing a suppressive peritoneal macrophage phenotype.","authors":"Thais Boccia, Victor Fattori, Matheus Deroco Veloso Da Silva, Nathan L Asquith, Weikang Pan, Michael S Rogers, Ivan Zanoni, Alex G Cuenca","doi":"10.1093/jimmun/vkaf206","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf206","url":null,"abstract":"Adjuvants are widely used to boost the immune response during vaccination protocols. Our group has previously reported that repeated intraperitoneal administration of alum in mice, known as adjuvant conditioning (AC), creates an immunosuppressive environment that delays allogeneic graft rejection through NLRP3-dependent MDSC expansion. However, little is known about the effects of AC on the reprogramming of peritoneal cavity cells, particularly the different peritoneal macrophage populations, and the impact on the adaptive immune response. We found a population-specific immune response to alum, with small peritoneal macrophages (SPMs) being more prone to inflammasome activation than large peritoneal macrophages (LPMs) in vitro. In vivo, alum exposure led to NLRP3-dependent macrophage disappearance reaction (MDR) of LPMs, which could be explained by aggregate formation and migration to the omentum. AC also induced the reprogramming of resident macrophages and infiltrating monocytes towards a less inflammatory state, making them more vulnerable to bacterial infections, but recruited neutrophils with enhanced killing ability. This suggests that AC may influence both innate and adaptive immunity in distinct ways, reprogramming cells to different profiles, and indicating its potential as an immunosuppressive treatment for autoimmune diseases and transplant rejection.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glucocorticoid-induced Pneumocystis pneumonia mice developed immune reconstitution inflammatory syndrome after glucocorticoid withdrawal. 糖皮质激素诱导的肺囊虫肺炎小鼠在停用糖皮质激素后出现免疫重建炎症综合征。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-01 DOI: 10.1093/jimmun/vkaf071

Yawei Guo, Liuluan Zhu, Haichao Li

{"title":"Glucocorticoid-induced Pneumocystis pneumonia mice developed immune reconstitution inflammatory syndrome after glucocorticoid withdrawal.","authors":"Yawei Guo, Liuluan Zhu, Haichao Li","doi":"10.1093/jimmun/vkaf071","DOIUrl":"10.1093/jimmun/vkaf071","url":null,"abstract":"Mortality from Pneumocystis pneumonia (PCP) continues to increase among non-human immunodeficiency virus (HIV) patients. Previous studies have reported that a considerable proportion of patients experience deterioration of their disease when glucocorticoids or other immunosuppressants are withdrawn. However, the underlying mechanisms responsible for this phenomenon remain poorly understood. Our findings, based on a comparative analysis of immune function in glucocorticoid-induced PCP mice at the time of glucocorticoid continuation and glucocorticoid withdrawal, suggested that the damage to lung tissues in PCP mice was significantly exacerbated and lung function deteriorated following glucocorticoid withdrawal. Mechanistically, our investigations revealed that PCP mice underwent immune reconstitution and developed immune reconstitution inflammatory syndrome (IRIS) after glucocorticoid withdrawal, which resulted in enhanced immune responses to pre-existing Pneumocystis. Prophylactic G-CSF neutralization in vivo prior to glucocorticoid withdrawal attenuated withdrawal-induced IRIS but also impaired Pneumocystis clearance. This study elucidated that the exacerbation of infection in PCP mice after glucocorticoid withdrawal is analogous to the clinical phenomenon and demonstrated that it is caused by the immune reconstitution that occurs after glucocorticoid withdrawal and resulting IRIS while also showing that G-CSF plays an important role in this process. This provides clinical comprehension of the progression of disease in non-HIV PCP patients.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"2298-2306"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A translational approach to improve therapeutics in atopic dermatitis and beyond. 一种改善特应性皮炎及其他疾病治疗的转化方法。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-01 DOI: 10.1093/jimmun/vkaf049

Daniel Liu, Dev Patel, Megan Lau, Joseph Largen, Benjamin D Hu, Helen He, Emma Guttman-Yassky

{"title":"A translational approach to improve therapeutics in atopic dermatitis and beyond.","authors":"Daniel Liu, Dev Patel, Megan Lau, Joseph Largen, Benjamin D Hu, Helen He, Emma Guttman-Yassky","doi":"10.1093/jimmun/vkaf049","DOIUrl":"10.1093/jimmun/vkaf049","url":null,"abstract":"Atopic dermatitis (AD) and alopecia areata are highly prevalent inflammatory skin/hair conditions. While previously not fully understood and limited in treatment options, AD is currently undergoing a therapeutic revolution. Our increased understanding of the underlying immunologic and barrier dysregulations and disease heterogeneity across its spectrum is facilitating hypothesis-driven therapeutic development. Early transcriptomic analyses in AD skin and blood have identified disease-specific biomarkers and uncovered immune and barrier abnormalities that may contribute to disease pathogenesis. From these findings, various therapeutic targets were then proposed and investigated in clinical trials, leading to the Food and Drug Administration approval of several biologics and small molecule drugs that are now widely used in the clinical setting. Molecular phenotyping of patient samples before and after treatment has further elucidated the specific immunomodulatory effect of each therapeutic, as well as the relative contributions of various immune pathways to disease pathogenesis. This bench-to-bedside cyclical approach has rapidly broadened our understanding of AD and enabled the rapid expansion of the AD therapeutic pipeline. In this brief review, we detail how molecular and blood profiling studies in AD laid the foundation for a therapeutic revolution, discuss currently approved and potential therapeutics for AD resulting from this bench-to-bedside approach, and highlight how this translational approach is being applied to advancing the therapeutic pipeline of alopecia areata.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"2165-2179"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MHC II-restricted presentation of soluble antigen by naïve B cells is impaired upon engagement with membrane-associated antigen: A potential mechanism to mitigate autoreactivity. MHC ii -可溶性抗原的限制性递呈naïve B细胞在与膜相关抗原接触时受损：减轻自身反应性的潜在机制。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-01 DOI: 10.1093/jimmun/vkaf129

Thiago M Steiner, Yu Kato, Peck Szee Tan, Kirsteen M Tullett, Fatma Panetta, Gayle M Davey, Hidde L Ploegh, Mireille H Lahoud, Daniel Fernandez-Ruiz, Irina Caminschi, William R Heath

{"title":"MHC II-restricted presentation of soluble antigen by naïve B cells is impaired upon engagement with membrane-associated antigen: A potential mechanism to mitigate autoreactivity.","authors":"Thiago M Steiner, Yu Kato, Peck Szee Tan, Kirsteen M Tullett, Fatma Panetta, Gayle M Davey, Hidde L Ploegh, Mireille H Lahoud, Daniel Fernandez-Ruiz, Irina Caminschi, William R Heath","doi":"10.1093/jimmun/vkaf129","DOIUrl":"10.1093/jimmun/vkaf129","url":null,"abstract":"T cell tolerance to self can prevent self-reactive B cells from mounting effective autoimmune responses by limiting their available help. However, tolerance may be compromised during infection if small amounts of soluble cross-reactive pathogen antigens containing functional T cell epitopes are released for capture by activated B cells. Here, we assess this scenario and show that naïve B cells engaged and activated by membrane-bound antigens lacking T helper epitopes are impaired in their ability to capture and present additional soluble antigens containing T helper epitopes. This limits their ability to acquire help from cognate CD4+ T cells required for effective antibody responses. Failure to capture and present soluble antigen is due to IgM and IgD downregulation when engaged with membrane-bound antigen. Interestingly, IgG+ B cells are not similarly constrained and effectively capture soluble antigens. Our findings suggest control of naïve B cell tolerance partially depends on efficient receptor downregulation upon antigen engagement.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"2189-2201"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A breakthrough in the genetic and functional understanding of type I conventional dendritic cells. 在I型常规树突状细胞的遗传和功能理解方面的突破。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-01 DOI: 10.1093/jimmun/vkaf178

Boris Reizis

引用次数: 0

CD16a pairs form the basal molecular subunit for the NK-cell ADCC lytic synapse. CD16a对构成nk细胞ADCC裂解突触的基本分子亚基。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-01 DOI: 10.1093/jimmun/vkaf077

Patrick Ross, Tania Cid, Monica Fernández Quintero, Johannes Loeffler, Hijab Fatima, Dan P Leaman, Jessica Matthias, Kathryn Spencer, Michael B Zwick, Scott C Henderson, Andrew B Ward, Emily M Mace, Charles Daniel Murin

{"title":"CD16a pairs form the basal molecular subunit for the NK-cell ADCC lytic synapse.","authors":"Patrick Ross, Tania Cid, Monica Fernández Quintero, Johannes Loeffler, Hijab Fatima, Dan P Leaman, Jessica Matthias, Kathryn Spencer, Michael B Zwick, Scott C Henderson, Andrew B Ward, Emily M Mace, Charles Daniel Murin","doi":"10.1093/jimmun/vkaf077","DOIUrl":"10.1093/jimmun/vkaf077","url":null,"abstract":"NK cells utilize effector functions, including antibody-dependent cellular cytotoxicity (ADCC), for the clearance of viral infection and cellular malignancies. While antibody-induced clustering of FcγRIIIa (CD16a) is thought to drive ADCC, the molecular basis for this activity has not been fully described. We used MINFLUX nanoscopy to map the spatial distribution of CD16a within the NK-cell ADCC immune synapse. In both resting and NK cells activated on supported lipid bilayers by Trastuzumab, we detected pairs of CD16a molecules approximately 18 nm apart that could be homodimers. NK-cell activation results in a modest increase of clusters of 4 or more CD16a localizations without a change in cluster characteristics, while CD16a pair distances do not significantly change, suggesting that subtle structural changes underpin ADCC-based activation. Our results provide the highest spatial resolution yet described for CD16a imaging, offering insight into how CD16a organization within the immune synapse could influence ADCC activity.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"2180-2188"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Defining key parameters of therapeutic activity using mouse cancer neoepitopes. 利用小鼠肿瘤新表位确定治疗活性的关键参数。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-01 DOI: 10.1093/jimmun/vkaf090

Summit Singhaviranon, Joseph P Dempsey, Hakimeh Ebrahimi-Nik, Pramod Kumar Srivastava

{"title":"Defining key parameters of therapeutic activity using mouse cancer neoepitopes.","authors":"Summit Singhaviranon, Joseph P Dempsey, Hakimeh Ebrahimi-Nik, Pramod Kumar Srivastava","doi":"10.1093/jimmun/vkaf090","DOIUrl":"10.1093/jimmun/vkaf090","url":null,"abstract":"Cancer neoepitopes have emerged as strong candidates as cancer vaccines. Mouse models of cancer neoepitopes often test their activity in models of prophylaxis, while the human setting is always in therapy of preexisting disease. We have previously identified 7 MHC I-presented cancer neoepitopes of the BALB/c sarcoma Meth A by mass spectrometry; 3 of the 7 neoepitopes showed anti-tumor activity in assays of prophylaxis. Here, we test these neoepitopes for activity in treatment of preexisting 3-, 10- and 17-d old cancers, and observe that: (i) activity in prophylaxis is not predictive of efficacy in treatment of preexisting cancers. (ii) The higher activity of a neoepitope in therapy, albeit not in prophylaxis, correlates well with the high precursor frequency of CD8 T cells. (iii) Co-immunization with CD4 and CD8 neoepitopes is essential for optimal therapeutic efficacy. CD4 help can be obtained from an MHC II-restricted neoepitope of the tumor, or from an irrelevant MHC II-epitope. (iv) The CTL and helper epitopes, linked or un-linked to each other, are equally effective. These insights stress and stretch some of our current suppositions and shall inform designs for use of neoepitopes in cancer treatment.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"2425-2433"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0