(1) Background: The expression of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), an immune checkpoint receptor on T cells, has been associated with dismal outcomes and advanced tumor stages in various solid tumors. The blockade of TIM-3 is currently under examination in several clinical trials. This study examines TIM-3 expression in high-risk soft tissue sarcomas (HR-STS). (2) Methods: Tumor cell expression of TIM-3 on protein level was analyzed in pre-treatment biopsies of patients with HR-STS. TIM-3 expression was correlated with clinicopathological parameters including tumor-infiltrating lymphocyte (TIL) counts, programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PDL-1) expression in patients with HR-STS. Survival dependent on the expression of TIM-3 was analyzed. (3) Results: TIM-3 expression was observed in 101 (56%) out of 179 pre-treatment biopsies of patients with HR-STS. TIM-3 expression was significantly more often observed in undifferentiated pleomorphic sarcomas (UPS) compared to other histological subtypes ( < 0.001), high TIL counts ( < 0.001), and high PD-1 ( < 0.001) and PD-L1 expression ( < 0.001). TIM-3 expression did not have a prognostic impact on survival in patients with HR-STS. (4) Conclusions: This is the first study to demonstrate a significant tumor cell expression of TIM-3 in specific subsets of patients with HR-STS. TIM-3 qualifies as a potential immunotherapeutic target in HR-STS.
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http://dx.doi.org/10.3390/cancers15102735 | DOI Listing |
Staphylococcus aureus prosthetic joint infections (PJIs) are broadly considered incurable, and clinical diagnostics that guide conservative vs. aggressive surgical treatments do not exist. Multi-omics studies in a humanized NSG-SGM3 BLT mouse model demonstrate human T cells: 1) are remarkably heterogenous in gene expression and numbers, and 2) exist as a mixed population of activated, progenitor-exhausted, and terminally-exhausted Th1/Th17 cells with increased expression of immune checkpoint proteins (LAG3, TIM-3).
View Article and Find Full Text PDFClin Colorectal Cancer
December 2024
Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland. Electronic address:
Background: Special AT-rich binding protein-2 (SATB2) is a nuclear matrix associated protein regulating gene expression which is normally expressed in colonic tissue. Loss of SATB2 expression in colorectal cancer (CRC) has negative implications for prognosis and has been associated with chemotherapy resistance. Furthermore, recent evidence suggests SATB2 may influence immune checkpoint (IC) expression.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Background: The transmembrane protein T-cell immunoglobulin and mucin-domain containing molecule 3 (TIM-3) is an immune checkpoint receptor that is expressed by a variety of leukocyte subsets, particularly in the tumor microenvironment. An effective TIM-3-targeting therapy should account for multiple biological factors, including the disease setting, the specific cell types involved and their varying sensitivities to the four putative TIM-3 ligands (galectin-9, phosphatidylserine, high mobility group protein B1 and carcinoembryonic antigen cell adhesion molecule 1), each of which engages a unique binding site on the receptor's variable immunoglobulin domain. The primary objectives of this study were to assess the prevalence and function of TIM-3 natural killer (NK) cells in patients with head and neck squamous cell carcinoma (HNSCC), determine whether the four TIM-3 ligands differentially affect TIM-3 NK cell functions, identify the most immunosuppressive ligand, and evaluate whether targeting ligand-mediated TIM-3 signaling enhances NK cell effector functions.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University, 66421 Homburg, Germany.
Head and neck squamous cell carcinomas (HNSCC) have an overall poor prognosis, especially in locally advanced and metastatic stages. In most cases, multimodal therapeutic approaches are required and show only limited cure rates with a high risk of tumor recurrence. Anti-PD-1 antibody treatment was recently approved for recurrent and metastatic cases but to date, response rates remain lower than 25%.
View Article and Find Full Text PDFBiomedicines
November 2024
Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.
Compared to other immune checkpoint molecules, T cell immunoglobulin domain and mucin domain-3 (TIM-3) is highly expressed on natural killer (NK) cells, but its functional role and prognostic significance in acute myeloid leukemia (AML) remains unclear. This study aims to evaluate the role of TIM-3 expression on the cytotoxic and killing capacity of NK cells and its prognostic significance in AML. AML public single-cell RNA sequencing (scRNAseq) data were used to analyze the correlation of transcript levels between (encoding TIM-3) and cytotoxic molecules in NK cells.
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