Antigen-specific CD4 T cell polarization is altered by immune checkpoint blockade in pancreatic ductal adenocarcinoma
نویسندگان
چکیده
Abstract Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy with poor response to conventional immune checkpoint inhibitors. Early data by our group suggests CD4 T cell depletion abrogates novel combination therapy that transiently curative in murine model of PDA. Given the importance cells PDA control, we now seek describe dynamics at an antigen-specific resolution. To this end, developed tetramer reagent towards recently identified MHC class II epitope. Through this, observe T-cell polarization distinct from bulk population both spleen and tumor microenvironment. Tumor-specific also displayed differential during therapy, suggesting positive mediated part TCR-dependent stimulation compartment.
منابع مشابه
Pancreatic Ductal Adenocarcinoma Contains an Effector and Regulatory Immune Cell Infiltrate that Is Altered by Multimodal Neoadjuvant Treatment
OBJECTIVE The immune response to pancreatic ductal adenocarcinoma (PDA) may play a role in defining its uniquely aggressive biology; therefore, we sought to clearly define the adaptive immune infiltrate in PDA. DESIGN We used immunohistochemistry and flow cytometry to characterize the immune infiltrate in human PDA and compared our findings to the patients' peripheral blood. RESULTS In cont...
متن کاملCytotoxic T lymphocyte antigen-4 and immune checkpoint blockade.
The relationship between cancer and the immune system is complex and provides unique therapeutic opportunities. Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a regulatory molecule that suppresses T cell effector function following initial activation by costimulatory signals. Fully human monoclonal antibodies targeting CTLA-4 have been shown to increase T cell function and antitumor responses in ...
متن کاملCytotoxic T lymphocyte antigen - 4 and immune checkpoint blockade
Introduction The immune system is an important defense against the development and progression of cancer (1). Historically, there has been a waxing and waning enthusiasm for immune therapies to treat cancer due to limited efficacy. Immunotherapies, such as IL-2 and adoptive transfer of autologous tumor-infiltrating lymphocytes, can induce durable tumor responses in a subset of patients, leading...
متن کاملCarcinoembryonic antigen-specific but not antiviral CD4+ T cell immunity is impaired in pancreatic carcinoma patients.
Pancreatic carcinoma is a very aggressive disease with dismal prognosis. Although evidences for tumor-specific T cell immunity exist, factors related to tumor microenvironment and the presence of immunosuppressive cytokines in patients' sera have been related to its aggressive behavior. Carcinoembryonic Ag (CEA) is overexpressed in 80-90% of pancreatic carcinomas and contains epitopes recognize...
متن کاملAntigen-specific T-T interactions regulate CD4 T-cell expansion.
The regulation of CD4 T-cell numbers during an immune response should take account of the amount of antigen (Ag), the initial frequency of Ag-specific T cells, the mix of naive versus experienced cells, and (ideally) the diversity of the repertoire. Here we describe a novel mechanism of T-cell regulation that potentially deals with all of these parameters. We found that CD4 T cells establish a ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.86.10