Intestinal intraepithelial T lymphocytes express the α E subunit of integrin αEβ7, which is detected by antibodies to CD103. Accordingly, within T-cell neoplasms, CD103 reactivity has most frequently been reported in enteropathy-associated T-cell lymphomas, which are postulated to arise from intestinal intraepithelial T lymphocytes. However, prior studies of CD103 expression in T-cell neoplasms have been limited by the requirement for fresh or frozen tissue, given the historic lack of an antibody to CD103 for use in paraffin-embedded sections. Thus, a thorough assessment of CD103 expression in a broad spectrum of T-cell neoplasms as categorized by the current classification system has not yet been performed. This study uses a newly described antibody to define the profile of CD103 immunoreactivity in paraffin sections of a wide variety of T-cell neoplasms (184 cases). Overall, 22 T-cell neoplasms (12%) were CD103 positive, including 7 of 15 gastrointestinal lymphomas (3.8% of total cases; 46% of gastrointestinal cases). In intestinal cases, CD103 positivity did not correlate with morphology, presence or absence of enteropathy, or immunohistochemical profile. A history of celiac disease was not documented in any case. Frequent but inconsistent reactivity was also noted for adult T-cell leukemia/lymphoma with 4 of 10 cases (40%) positive. In the remaining T-cell neoplasms representing most entities within the current World Health Organization classification, CD103 reactivity was sporadically observed in 11 of 159 cases (6.9%). CD103 positivity is an unusual feature in T-cell neoplasms and tends to occur in gastrointestinal lymphomas and adult T-cell leukemia/lymphoma but is not a consistent characteristic of these neoplasms.
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http://dx.doi.org/10.1097/PAS.0000000000000296 | DOI Listing |
Science
January 2025
NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA, USA.
The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid-CoA:amino acid -acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy.
View Article and Find Full Text PDFCancer Med
January 2025
Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland.
Background: Immune checkpoint inhibition therapies have provided remarkable results in numerous metastatic cancers, including mismatch repair-deficient (dMMR) colorectal cancer (CRC). To evaluate the potential for PD-1 blockade therapy in a large population-based cohort, we analyzed the tumor microenvironment and reviewed the clinical data and actualized treatment of all dMMR CRCs in Central Finland province between 2000 and 2015.
Material And Methods: Of 1343 CRC patients, 171 dMMR tumors were identified through immunohistochemical screening.
JCI Insight
January 2025
Center for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology and Krantz Family Center for Cancer Research, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
CD4+ T cells contribute to antitumor immunity and are implicated in the efficacy of cancer immunotherapies. In particular, CD4+ T helper 2 (Th2) cells were recently found to block spontaneous breast carcinogenesis. However, the antitumor potential of Th2 cells in targeting established breast cancer remains uncertain.
View Article and Find Full Text PDFJCI Insight
January 2025
Department of Immunology and.
Tumor-associated macrophages (TAMs) are one of the key immunosuppressive components in the tumor microenvironment (TME) and contribute to tumor development, progression, and resistance to cancer immunotherapy. Several reagents targeting TAMs have been tested in preclinical and clinical studies, but they have had limited success. Here, we show that a unique reagent, FF-10101, exhibited a sustained inhibitory effect against colony-stimulating factor 1 receptor by forming a covalent bond and reduced immunosuppressive TAMs in the TME, which led to strong antitumor immunity.
View Article and Find Full Text PDFInt J Med Sci
January 2025
Medical Oncology Department of Gastrointestinal Cancer, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute, No.44 Xiaoheyan Road, Dadong District, Shenyang 110042, Liaoning Province, China.
Gastric cancer (GC) remains a significant global health challenge. This study aimed to comprehensively analyze GC epidemiology and risk factors to inform prevention and intervention strategies. We analyzed the Global Burden of Disease Study 2021 data, conducted 16 different machine learning (ML) models of NHANES data, performed Mendelian randomization (MR) studies on disease phenotypes, dietary preferences, microbiome, blood-based markers, and integrated differential gene expression and expression quantitative trait loci (eQTL) data from multiple cohorts to identify factors associated with GC risk.
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