Oncoimmunology最新文献

{"title":"Broad targeting of HPV E proteins by intratumoral and systemic B cell responses in HPV+ head and neck cancer.","authors":"Ilham Bahhar, Jacob P Conarty, Songzhu Zhao, Mengda Yu, Bhavna Kumar, James W Rocco, Andreas Wieland","doi":"10.1080/2162402X.2026.2728208","DOIUrl":"10.1080/2162402X.2026.2728208","url":null,"abstract":"<p><p>B cells can account for a substantial proportion of tumor-infiltrating lymphocytes (TILs) and have been associated with improved outcomes in several malignancies. Yet, their antigen specificity, a key factor for ascribing a distinct function, is mostly unknown. Here, we demonstrate that in tumors of patients with human papillomavirus-positive head and neck cancer (HPV+ HNC) a substantial proportion of intratumoral antibody-secreting cells (ASCs) are specific for HPV E proteins. Using IgG ELISpots on TILs, we show that HPV E protein-specific ASCs are detectable in virtually all patients and can account for up to almost a third of all intratumoral IgG+ ASCs. ASC responses against the viral proteins E1 and E2 consistently outnumbered those against the classic oncoproteins E6 and E7. HPV-specific intratumoral ASCs correlated strongly between primary tumor and metastatic lymph nodes as well as with plasma IgG titers, indicating that intratumoral tumor-specific ASCs, at least partially, contribute to systemic anti-tumor responses. To further resolve the makeup of tumor-specific antibody responses, we developed a novel Multiplex Antigen Flow-based ImmunoAssay (MAFIA) enabling simultaneous and standardized quantification of HPV E-specific antibodies across all major Ig isotypes and IgG subclasses. Applying MAFIA to plasma samples of patients with HPV+ HNC revealed that HPV-specific plasma antibodies mainly consisted of IgG1, IgG3, and IgA, with the highest median responses directed against E1 and E2. Overall, our study delineates the antigenic hierarchy and makeup of HPV-specific humoral responses in HPV+ HNC, both intratumorally and systemically, thus providing a framework for future biomarker as well as next-generation therapeutics development.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2728208"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901369","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":"HLA-G functions as a tumor-intrinsic driver of growth and survival in renal cell carcinoma.","authors":"Ashwin Ajith, Aparna Geetha Jayaprasad, Useong Chang, Arsha Sreekumar, Mia Lin, Valia Bravo-Egana, Laura L Mulloy, Daniel David Horuzsko, Edgardo D Carosella, Anatolij Horuzsko","doi":"10.1080/2162402X.2026.2717680","DOIUrl":"https://doi.org/10.1080/2162402X.2026.2717680","url":null,"abstract":"<p><p>HLA-G is a non-classical MHC class I molecule with potent immunoregulatory functions that is aberrantly expressed in multiple malignancies, yet its tumor-intrinsic role remains poorly defined. To characterize this potential oncogenic role of HLA-G in clear cell renal cell carcinoma (ccRCC), we utilized integrated transcriptomic, in vitro, and in vivo approaches. Analysis of the Cancer Genome Atlas (TCGA) ccRCC cohort revealed that elevated HLA-G expression was associated with immunosuppressive programs and cell populations. Interrogation of a publicly available ccRCC single-cell RNA sequencing dataset revealed that HLA-G expression within tumor epithelial clusters is associated with hypoxia-driven, metabolic transcriptional programs. Multiplex immunofluorescence of human ccRCC specimens confirmed the presence of tumor cell-intrinsic HLA-G expression in advanced disease. Functional studies using RCC7 cells expressing the full-length canonical HLA-G isoform (RCC7/HLA-G1) demonstrated increased proliferation, migration, clonogenicity, cell-cycle progression, and resistance to apoptosis compared with HLA-G-negative RCC7wt cells. RCC7/HLA-G1 xenografts exhibited accelerated tumor growth accompanied by the activation of proliferative, stemness-related, and metabolic programs. Multi-omics analyses further revealed enhanced mitochondrial activity and redox metabolic adaptation in HLA-G-expressing tumors. Mechanistically, HLA-G expression was associated with increased VEGF-C expression and enhanced VEGFR3 signaling, suggesting the activation of a VEGF-C/VEGFR3-associated pro-survival pathway. In three-dimensional tumor spheroid immune cell co-culture models, HLA-G expression reduced CD8⁺ T-cell-mediated cytotoxicity while promoting regulatory T-cell expansion and macrophage polarization toward an immunosuppressive M2-like phenotype. Collectively, these findings establish HLA-G as a key contributor to tumor progression and immune suppression in ccRCC and support HLA-G as a promising therapeutic target.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2717680"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13475321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760092","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":"Immune cell clustering identifies a CD163⁺/CSF1R⁺ macrophage and neutrophil-enriched phenotype with distinct biological signatures and poor prognosis in angiosarcoma.","authors":"Adrian Georg Simon, Bastian Grothey, Su Ir Lyu, David Stahl, Lars Mortimer Schiffmann, Christiane Josephine Bruns, Peer Eysel, Reinhard Buettner, Roland Tillmann Ullrich, Alexander Quaas","doi":"10.1080/2162402X.2026.2647487","DOIUrl":"10.1080/2162402X.2026.2647487","url":null,"abstract":"<p><p>The tumor immune microenvironment (TIME) influences tumor biology and therapeutic response, yet its composition and clinical relevance in angiosarcoma, an ultrarare and aggressive sarcoma with a dismal prognosis, remain poorly defined. To address this gap, we comprehensively profiled the TIME of 63 angiosarcomas (AS), including primary cutaneous, secondary, and visceral subtypes, with a focus on colony-stimulating factor 1 receptor (CSF1R)-expressing tumor-associated macrophages (TAMs). Using conventional and multiplex immunohistochemistry with quantitative analysis, we found that CD68⁺/CD163⁺ (M2-like) TAMs predominated across all AS subtypes. The enrichment of CD68⁺/CD163⁺/CSF1R⁺ TAMs was strongly associated with shorter overall and disease-free survival. Unsupervised clustering revealed three immune phenotypes, among which a CSF1R-high macrophage/neutrophil-enriched cluster was independently associated with poor overall survival. Proteomic profiling of these high-risk angiosarcomas within this cluster demonstrated upregulation of oxidative phosphorylation, angiogenesis, and neutrophil-associated pathways, alongside downregulation of extracellular matrix organization, indicating a metabolically distinct and immunologically myeloid-driven tumor state and immune phenotype. These findings identify CSF1R⁺ macrophage enrichment as a defining feature of high-risk angiosarcoma and suggest that improved biological understanding of the CSF1R axis may allow additional immunomodulatory therapeutic strategies in this rare and aggressive malignancy.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2647487"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13011603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147500211","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":"Immune evasion in locally advanced mismatch repair-deficient microsatellite instability-high colorectal cancer: Reduced T-cell infiltration and upregulation of epithelial IDO1 expression.","authors":"Sabina Niyazova, Christine Sers, Hendrik Bläker, David Horst, Wolfgang Schmitt, Zehra Karadeniz, Simon Schallenberg, Alexej Ballhausen, Dominik P Modest, Colin M Krüger, Eric P M Lorenz, Michael Hünerbein, Arndt von Kirchbach, Armin Jarosch","doi":"10.1080/2162402X.2026.2700837","DOIUrl":"10.1080/2162402X.2026.2700837","url":null,"abstract":"<p><p>Early-stage colorectal cancer (CRC) with confirmed microsatellite instability generally has a favorable prognosis associated with pronounced immune infiltration. However, some patients still develop metastases. The underlying mechanisms, particularly those related to the tumor immune microenvironment, remain incompletely understood. The study included tissue samples from 217 patients with dMMR/MSI-H CRC, comprising 89 stage III/IV and 128 stage I/II cases. Tissue microarrays and immunohistochemical analyzes were performed for all cases. We evaluated immune markers identifying T cells, B cells, dendritic cells, natural killer cells, macrophages, immunosuppressive markers, and immune checkpoint targets in epithelial and stromal compartments, and additionally performed a cohort-derived immune infiltration score (IIS). The survival analysis assessed the prognostic impact of immune markers stratified by tumor stage. Stage I/II dMMR/MSI-H CRCs showed significantly higher CD3⁺ T-cell and natural killer cell levels, higher IIS metrics across all regions, and higher CD4⁺ T helper cell levels in the stroma. Stage III/IV cases exhibited increased epithelial expression of indoleamine 2,3-dioxygenase 1. Given the limited number of stage IV patients, an additional stage III vs. stage I/II comparison was performed, revealing that these immune differences were already evident at the level of nodal progression. In addition, CD3⁺, CD4⁺, and CD8⁺ T cells and the IIS showed varying prognostic associations across tumor stages. These findings suggest that the overall immunogenicity and prognostic relevance of immune markers in dMMR/MSI-H CRC depend on tumor stage. Immune profiling could be used for early-stage patient stratification and also suggests the potential benefit of early immunotherapeutic intervention.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2700837"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13353779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148425651","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":"Profiling tumor immune microenvironment of epithelial ovarian carcinoma.","authors":"Zeinab Dehghani-Ghobadi, Vasilis S Dionellis, Clara Traber, Jonathan S Moore, Nicolas Samartzis, Stephan Ryser, Dimitrios R Kalaitzopoulos, Nicolas Liaudet, Clothilde Ferreira, Valentine Du Bois, Paula Stancl, Rosa Karlic, Mathias Choschzick, Aurelia Noske, José L Sandoval, Eleftherios Pierre Samartzis, Intidhar Labidi-Galy","doi":"10.1080/2162402X.2026.2722470","DOIUrl":"10.1080/2162402X.2026.2722470","url":null,"abstract":"<p><strong>Background: </strong>Epithelial ovarian carcinoma (EOC) comprises five main histological subtypes: high-grade serous (HGSOC), low-grade serous (LGSOC), clear cell (CCOC), mucinous (MOC), and endometrioid (ENOC). Each histotype harbors specific genomic alterations and clinical outcome. Few studies systematically compared the tumor immune microenvironment across the five subtypes.</p><p><strong>Methods: </strong>We performed 7-plex (CD45, CD8, CD68, CD163, FoxP3, CD20, and cytokeratin) sequential immunohistochemistry on a clinically annotated tissue microarray including 139 EOC representing the five subtypes and 26 borderline tumors (serous and mucinous). Digital pathology was used to quantify immune cell abundance, their spatial distribution (stroma vs tumor core), and correlation with survival.</p><p><strong>Results: </strong>Immune cells were dominated by macrophages and more abundant in the stroma than tumor core across the five subtypes, consistent with immune excluded pattern. Compared to HGSOC, CCOC displayed the highest infiltration by CD45⁺ leukocytes and CD68⁺ macrophages, particularly M2-like CD163⁺ cells, suggesting a macrophage-rich, immunosuppressive phenotype. LGSOC exhibited the highest infiltration by intraepithelial FoxP3⁺ regulatory T cells. Comparison of borderline tumors with invasive carcinoma (LGOSC and MOC) revealed that malignant progression is accompanied by loss of CD8⁺ T cells, enrichment in regulatory T cells and increase of CD163⁺/CD68⁺ ratio, consistent with immune evasion during tumorigenesis. There was a trend toward better survival in HGSOC highly infiltrated by lymphocytes, either intraepithelial (CD8⁺ and FoxP3⁺) or stromal (FoxP3⁺ and CD20⁺).</p><p><strong>Conclusions: </strong>EOC is characterized by histotype-specific immune milieux defined by macrophage dominance, epithelial immune exclusion and dynamic immune remodeling during progression from borderline tumors to invasive carcinomas.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2722470"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13568574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931777","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":"Single-cell landscape of peripheral and tumor-infiltrating immune cells in HPV-negative HNSCC.","authors":"Rômulo Gonçalves Agostinho Galvani, Adolfo Alexis Rojas Hidalgo, Carlos Alberto Biagi-Junior, Bruno Fernandes Matuck, Jelte Martinus Maria Krol, Brittany Rupp, Nikhil Kumar, Khoa Huynh, Jinze Liu, Siddharth Sheth, Vinicius Maracaja-Coutinho, Kevin Matthew Byrd, Patricia Severino","doi":"10.1080/2162402X.2025.2605741","DOIUrl":"10.1080/2162402X.2025.2605741","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. HPV-negative HNSCC, arising in diverse upper airway mucosal niches, is particularly aggressive, with poor 5-y survival and a limited response to immune checkpoint inhibitors. A deeper understanding of the tumor-localized immune landscape is essential to uncover actionable immunotherapeutic targets. Here, we integrated two single-cell RNA sequencing (scRNA-seq) datasets from 29 samples totaling nearly 300,000 immune cells to dissect immune rewiring during tumor progression and lymph node metastasis in HPV-negative HNSCC. We identified distinct shifts in adaptive immune cell populations across 14 peripheral blood mononuclear cell (PBMC) and 21 tumor-infiltrating immune cell (TIC) states. Notably, TICs exhibited enriched interferon response and immunomodulatory gene signatures, in contrast to PBMCs, indicating tumor-specific immune imprinting. Ligand-receptor analysis revealed that immunosuppressive crosstalk between macrophages and cytotoxic cells was associated with advanced disease. To spatially validate these transcriptional states, we conducted multiplexed immunofluorescence profiling on nine locally invasive HPV-negative HNSCCs, all from the ventrolateral tongue mucosa. Spatial proteomics confirmed peritumoral enrichment of activated (CD107a⁺, ICOS⁺) NK and CD8⁺ T cells and intratumoral accumulation of exhausted (PD-1⁺, PD-L1⁺) phenotypes, mirroring pseudotime trajectories inferred from scRNA-seq. These findings highlight spatially localized cytotoxic cell exhaustion as a key immune evasion mechanism in HPV-negative HNSCC and underscore the value of integrating spatial and single-cell data to reveal therapeutic vulnerabilities.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2605741"},"PeriodicalIF":6.5,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145858554","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":"Oncolytic virus OVV-03 enhances CAR-T cell therapy against glioblastoma via immune modulation and specific HER2 upregulation.","authors":"Yi Tang, Qinzhi E, Liang Ma, Xuetao Li, Yang Zhang, Weichao Wang, Zuoyu Jiang, Xuewen Zhang, Yingbo Hou, Jiaming Du, Yang Zhu, Hanmiao Dong, Yeyang Xu, Ting Tian, Longxin Cheng, Qibin Ma, Jian Li, Guoqing Zhou, Yulun Huang","doi":"10.1080/2162402X.2025.2612377","DOIUrl":"10.1080/2162402X.2025.2612377","url":null,"abstract":"<p><p>Glioblastoma (GBM) remains therapeutically challenging due to treatment resistance and immunosuppression. Oncolytic virotherapy offers a promising strategy. This study engineered OVV-03, a novel HER2-armed oncolytic vesicular stomatitis virus (VSV), and evaluated its efficacy against GBM. OVV-03 demonstrated potent infectivity and cytotoxicity in GBM cell lines and patient-derived cells, inducing caspase-dependent apoptosis and suppressing proliferation/clonogenicity. In murine GBM models, OVV-03 significantly suppressed tumor growth, improved survival, and enhanced CD8⁺ T cell infiltration. Single-cell RNA sequencing revealed OVV-03 remodels the tumor immune microenvironment by boosting cytotoxic T cell activity and inhibiting immunosuppressive pathways, notably PD-L1/PD-1 signaling. Mechanistically, OVV-03 downregulated PD-L1 by inhibiting the JNK-c-Fos/c-Jun axis, reversible by TNF-<i>α</i> stimulation. Critically, OVV-03 synergized with B7H3- or HER2-targeted CAR-T cells, inducing superior tumor regression and prolonged survival in orthotopic models. These findings demonstrate that OVV-03 exerts potent antitumor effects through direct oncolysis and immune activation, including PD-L1 modulation. Its synergistic combination with CAR-T cells highlights OVV-03 as a highly promising oncolytic immunovirotherapy platform for GBM.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2612377"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12785206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913733","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":"Trial Watch - bispecific T cell engagers and higher-order multispecific immunotherapeutics.","authors":"Enfu Xue, Xiaolian Deng, Flora Doffe, Guido Kroemer, Oliver Kepp","doi":"10.1080/2162402X.2026.2632421","DOIUrl":"10.1080/2162402X.2026.2632421","url":null,"abstract":"<p><p>Over the past decades, cancer immunotherapy has evolved into clinical practice, with bispecific T cell engagers (TCEs) and other higher-order multispecific immunotherapeutics emerging as approaches for precision immune modulation. These engineered antibodies redirect immune effector cells toward tumor targets, thereby eliciting coordinated antitumor immune responses. While substantial clinical success has been achieved in hematologic malignancies, major challenges, such as limited activity in solid tumors, continue to constrain broader application. In this Trial Watch, we summarize recent preclinical advances in the design and optimization of TCEs and multispecific immune engager platforms together with available clinical trial data. We further examine key pharmacokinetic, safety, resistance, and manufacturing considerations in immune engager development. Collectively, these findings highlight the increasing versatility of immune cell-redirecting immunotherapies and their pivotal role in shaping the next generation of precision cancer therapy.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2632421"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146208017","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":"KRAS-elicited PDIA6 blocks PERK-dependent immunogenic cell death in pancreatic carcinoma.","authors":"Liwei Zhao, Peng Liu, Guido Kroemer, Oliver Kepp","doi":"10.1080/2162402X.2026.2641424","DOIUrl":"10.1080/2162402X.2026.2641424","url":null,"abstract":"<p><p>KRAS-mutant pancreatic ductal adenocarcinoma (PDAC) remains largely refractory to immune checkpoint blockade. Wang et al. identified PDIA6 as a KRAS-driven suppressor of PERK-dependent immunogenic cell death, fostering immune exclusion. PDIA6 inhibition restores CD8⁺ T-cell immunity and sensitizes PDAC to immunotherapy, highlighting a targetable resistance mechanism in KRAS-mutant PDAC.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2641424"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12973465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379244","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":"Intratumoral enrichment and suppressive activity of DP8α regulatory T cells in human colorectal cancer.","authors":"Mathilde Deiber, Cécile Deleine, Nadine Gervois-Segain, Francine Jotereau, Nathalie Labarrière, Frédéric Altare, Anne Jarry, Emmanuelle Godefroy","doi":"10.1080/2162402X.2026.2696069","DOIUrl":"10.1080/2162402X.2026.2696069","url":null,"abstract":"<p><p>Colorectal cancer (CRC) progression is driven by dynamic interactions among tumor cells, immune infiltrates, and the gut microbiota. While regulatory T cells (Tregs) may contribute to immune suppression in CRC, the role of non-conventional Tregs remains poorly defined. We identified a non-conventional population of microbiota-induced Tregs in the human colonic mucosa that co-expressed CD4, CD8α, CXCR6, and CCR6, termed DP8α Tregs, that exert potent immunomodulatory properties in different inflammatory settings. Their status and role in CRC, however, have not been investigated. Here, using multiparametric flow cytometry in a prospective cohort of CRC patients, we showed that DP8α Tregs are significantly enriched in tumors compared to paired non-tumoral colonic mucosa. Tumor-infiltrating DP8α Tregs displayed elevated expression of the CD39/CD73 ectonucleotidases, as well as CCR5, consistent with a suppressive phenotype within the tumor microenvironment. Functional co-culture assays further demonstrated that sorting DP8α Tregs from CRC tumors inhibited both CD4 and CD8 T-cell proliferation, an effect largely reversed by pharmacological inhibition of CD39 and CD73, which was associated with reduced IL-2 levels. Together, these findings show that DP8α Tregs enriched in the CRC tumor microenvironment, are able to suppress effector T-cell responses through the purinergic pathway and support further investigation of their contribution to immune regulation in CRC.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2696069"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148377616","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}