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ANXA10 sensitizes microsatellite instability-high colorectal cancer to anti-PD-1 immunotherapy via assembly of HLA-DR dimers by regulating CD74.
Cell Biol Toxicol
January 2025
Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, Liaoning, China.
Background: Microsatellite instability-high (MSI-H) metastatic colorectal cancer (CRC) patients are the dominant population in immune checkpoint blockade treatments, while more than half of them could not benefit from single-agent immunotherapy. We tried to identify the biomarker of MSI-H CRC and explore its role and mechanism in anti-PD-1 treatments. Tumor-specific MHC-II was linked to a better response to anti-PD-1 in MSI-H CRC and CD74 promoted assembly and transport of HLA-DR dimers.
View Article and Find Full Text PDFComparative Analysis of Systemic Immune Responses and Metastatic Risks in Tumor Ablation: An Animal Study of Radiofrequency Ablation and Irreversible Electroporation with Immune Modulation.
Cardiovasc Intervent Radiol
January 2025
Department of Immunology, Faculty of Medicine, Kindai University, Osaka, Japan.
Purpose: This study aimed to compare systemic immune responses and metastatic effects induced by radiofrequency ablation (RFA) and irreversible electroporation (IRE) in murine tumor models. We assessed cytokine production, growth of treated and untreated metastatic tumors, and synergy with immune checkpoint inhibitors (ICIs).
Materials And Methods: Hep55.
Bile acid synthesis impedes tumor-specific T cell responses during liver cancer.
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 PDFAnti-CTLA-4 generates greater memory response than anti-PD-1 via TCF-1.
Proc Natl Acad Sci U S A
January 2025
Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
The effects of T cell differentiation arising from immune checkpoint inhibition targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) on the immunological memory response remain unclear. Our investigation into the effects of anti-CTLA-4 and anti-PD-1 on memory T cell formation in mice reveals that memory T cells generated by anti-CTLA-4 exhibit greater expansion, cytokine production, and antitumor activity than those from anti-PD-1. Notably, anti-CTLA-4 preserves more T cell factor-1 (TCF-1)+ T cells during priming, while anti-PD-1 leads to more thymocyte selection-associated high mobility group box (TOX)+ T cells.
View Article and Find Full Text PDFPhase 2 Open-Label Trial of Brentuximab Vedotin with Pembrolizumab in PD-1 Pretreated Metastatic Non-Small Cell Lung Cancer and Metastatic Cutaneous Melanoma.
Clin Cancer Res
December 2024
Baylor University Medical Center, Dallast, Texas, United States.
Purpose: Brentuximab vedotin (BV) is hypothesized to selectively deplete T regulatory cells (Tregs) that express CD30 and re-sensitize tumors to anti-(PD-1) therapy. This study evaluated responses to BV+pembrolizumab post PD-1 and explored corresponding biomarkers.
Methods: 55 patients with metastatic non-small cell lung cancer (NSCLC) and 58 with metastatic cutaneous melanoma received ≥1 dose of BV+pembrolizumab.
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