Clinical & Translational Immunology最新文献

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148077796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148075398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148075397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterisation of tumor-infiltrating gamma-delta T cells in human colorectal cancer with MHC-I loss.","authors":"Tianming A Li, Luke T Quigley, Kok Fei Chan, David S Williams, Lisa A Mielke, Andreas Behren, Jessica Da Gama Duarte","doi":"10.1002/cti2.70097","DOIUrl":"10.1002/cti2.70097","url":null,"abstract":"<p><strong>Objectives: </strong>Gamma-delta (γδ) T cells have been associated with favorable prognoses across several malignancies, underscoring their potential as targets for novel immunotherapies. These unconventional T lymphocytes exhibit an intrinsic tropism for the tumor microenvironment, largely driven by their capacity to recognize stress-induced antigens characteristic of metabolically dysregulated tumors. Unlike the mechanism governing conventional cytotoxic CD8⁺ alpha-beta (αβ) T cells, γδ T-cell receptors can engage tumor cell moieties independent of major histocompatibility complex class-I (MHC-I) and human leukocyte class-I molecules. Therefore, γδ T cells may have a pivotal role in the immune response to beta-2 microglobulin-mutated MHC-I negative (MHC-I^-) colorectal cancers (CRCs) with deficient mismatch repair.</p><p><strong>Methods: </strong>To determine whether γδ T-cell mobilisation extends to diverse aetiologies of MHC-I loss, we used multispectral immunohistochemistry to stain 150 stage I-IV primary CRC tissues, across eight tissue microarrays.</p><p><strong>Results: </strong>Our investigation revealed MHC-I loss in ~30% of CRC primary tumors across all disease stages, with a notable increase in stromal γδ T-cell frequency and activation status among stage III cases. Importantly, these findings extend previous observations largely confined to mismatch repair-deficient CRC by demonstrating that stromal γδ T-cell enrichment associated with MHC-I loss also occurs in mismatch repair-proficient tumors, suggesting a broader role for γδ T cells in immune surveillance of MHC-I-deficient CRC.</p><p><strong>Conclusion: </strong>These data highlight the potential of γδ T cells in counteracting immune evasive MHC-I^- tumors, thereby offering a robust rationale for their strategic deployment in next-generation immunotherapy regimens.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 ","pages":"e70097"},"PeriodicalIF":3.4,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148066743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148066744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel case of autosomal recessive CARD11 loss-of-function underlying impaired antiviral immunity and a review of literature.","authors":"Hamish Anderson, Cecilia Verryt, Paula Keating, Thomas Saunders, Samuel Dalton, Barry D Hock, Liping Goddard, Kylie Drake, Anja Werno, John O'Donnell, Jeffrey R Stinson, Andrew L Snow, Kuang-Chih Hsiao","doi":"10.1002/cti2.70066","DOIUrl":"10.1002/cti2.70066","url":null,"abstract":"<p><strong>Objectives: </strong>Germline <i>CARD11</i> variants lead to a spectrum of disease depending on the effect of signalling augmentation or impairment. Autosomal recessive (AR) CARD11 loss-of-function (LOF) is rare with only 12 cases reported to date.</p><p><strong>Methods: </strong>Clinical and immunological information was collated for a patient with a homozygous <i>CARD11</i> p.(Arg379Pro) variant.</p><p><strong>Results: </strong>The patient (P1, aged 5, female) has a history of developmental delay and growth failure, severe early-onset asthma, impaired clearance of naturally acquired viruses and probable susceptibility to live attenuated vaccines (LAV). Genetic testing revealed that P1 has a hypomorphic homozygous novel missense variant in the coiled-coil (CC) domain of CARD11, leading to LOF. She has combined immunodeficiency with significant T and B cell defects, and impaired nuclear factor kappa B (NF-κB) activity in lymphocytes.</p><p><strong>Conclusion: </strong>We expand the phenotypic spectrum of CARD11-opathies by describing a patient homozygous for a novel AR LOF <i>CARD11</i> variant, demonstrating susceptibility to Japanese encephalitis and varicella LAV and impaired clearance of multiple naturally acquired respiratory viral infections. Inborn errors of immunity affecting the CARD11-BCL10-MALT1 (CBM) complex should be considered in individuals with LAV vaccine susceptibility and recurrent or persistent viral infections.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 ","pages":"e70066"},"PeriodicalIF":3.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148066637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Fc and complement activity of Fc-modified avelumab boosts anti-tumor activity but promotes NK cell fratricide.","authors":"Lachlan J Dobson, Barry D Hock, Ariana Ht Drabble, Liping Goddard, Judith L McKenzie, Sean A MacPherson, Alexander D McLellan","doi":"10.1002/cti2.70098","DOIUrl":"10.1002/cti2.70098","url":null,"abstract":"<p><strong>Objectives: </strong>The anti-PD-L1 antibody avelumab has demonstrated efficacy across multiple cancer types. Avelumab primarily blocks the PD-1/L1 immune checkpoint, while inducing antibody-dependent cellular cytotoxicity (ADCC) from CD16a⁺ NK cells. However, subsets of patients possess lower-affinity CD16a allotypes that limit ADCC capacity of monoclonal antibodies. In this study, we modified the Fc domain of avelumab with characterised mutations to enhance ADCC across all CD16a allotypes.</p><p><strong>Methods: </strong>Comparisons between the wild-type avelumab and modified 'AveFc5M' were carried out to assess the impacts of introduced mutations on PD-L1 blockade, ADCC induction and complement-dependent cytotoxicity (CDC) induction. To assess ADCC, a range of PD-L1⁺ target cells were coated with mab prior to incubation with effector cells, with both high- and low-affinity CD16a allotypes represented. Human serum was employed for assessing CDC.</p><p><strong>Results: </strong>Both antibodies exhibited equivalent PD-L1 blocking activity. Notably, the modified AveFc5M displayed significantly enhanced ADCC across diverse tumor cell-effector cell combinations. Fc mutations also conferred the ability to mediate complement-dependent cytotoxicity (CDC) against a PD-L1⁺ lymphoma cell line. However, short term activation of NK cells or long-term expansion on artificial antigen presenting cells, led to upregulation of PD-L1 on NK cells. Addition of avelumab or AveFc5M to these NK cell populations induced a marked reduction in viable NK cells via ADCC-mediated fratricide.</p><p><strong>Conclusion: </strong>These findings demonstrate that Fc engineering of avelumab can substantially augment ADCC and CDC activity against PD-L1⁺ tumors. However, the enhanced effector function of AveFc5M led to NK cell fratricide, potentially limiting NK cell-dominated anti-cancer responses.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 ","pages":"e70098"},"PeriodicalIF":3.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148066638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}