Despite limited clinical efficacy in large trials, dendritic cells (DC)-based immunization has yielded impressive responses in some patients. Key questions remain to be solved in order to optimize this therapeutic vaccine. Among them, the nature of the DC type used and its state of maturation are pivotal. Besides myeloid DC which are mostly used in clinical trials, a new DC type has been recently described resulting from the differentiation of monocytes in the presence of type I IFNs. In the present study, we analyze the features of type I IFNs DC generated in the presence of either IL-3 (IL-3-DC) or GM-CSF (GM-CSF-DC) and compare their capacity to respond to poly(I:C) and to subsequently trigger T-cell activation. The two DC types disclose a similar immunophenotype characterized by high levels of chemokines receptors, co-stimulatory and HLA molecules expression. After poly(I:C) maturation, both DC types display a marked upregulation of CD80, CD83 and CD86 and the same pattern of gene expression. In addition, poly(I:C) stimulated them to secrete IFN-alpha and IL-12p70. Both DC types elicit potent allogeneic reactions. Priming of autologous T cells by IL-3-DC or GM-CSF-DC pulsed with an HLA-A2 restricted melan-A derived peptide, lead to the expansion of peptide specific CTL secreting high amounts of IFN-gamma. We conclude that poly(I:C) matured IL-3-DC and GM-CSF-DC share similar phenotype and functional properties including the capacity to prime tumor-associated antigen specific CTL.
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http://dx.doi.org/10.1007/s00262-005-0664-7 | DOI Listing |
Inflamm Res
January 2025
Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, 610041, People's Republic of China.
Background: A significant association between immune cells and sepsis has been suggested by observational studies. However, the precise biological mechanisms underlying this association remain unclear. Therefore, we employed a Mendelian randomization (MR) approach to investigate the causal relationship between immune cells and genetic susceptibility to sepsis, and to explore the potential mediating role of blood metabolites.
View Article and Find Full Text PDFInflamm Res
January 2025
Departments of Oral Medicine, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong Province, China.
Mucosal-associated invariant T (MAIT) cells, a type of T lymphocytes with innate-like characteristics, are crucial in bridging innate and adaptive immunity. When activated, MAIT cells release various inflammatory molecules and swiftly respond to antigens. Notably, numerous studies highlight the significant impact of MAIT cells on tumors and various immune disorders by influencing the immune microenvironment.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Immunology Department, State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Background: Therapeutic efficacy of carcinoembryonic antigen (CEA)-specific chimeric antigen receptor (CAR) T cells against colorectal cancer (CRC) remains limited due to the unique characteristics and distinct microenvironments of tumor tissues. We modified CEA-specific CAR-T cells, aiming to stimulate endogenous CD8 T cell responses against neoantigens that were derived from CEA-positive tumors destroyed by the CAR T cells.
Methods: In a conventional CEA CAR (reg-CAR), we modified it to express lymphotactin XCL1 and interleukin (IL)-7 genes, constructing a modified 7XCL1-CAR.
Hepatol Commun
November 2024
Human Immunology Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.
Background: HCC develops in the context of chronic inflammation; however, the opposing roles the immune system plays in both the development and control of tumors are not fully understood. Mapping immune cell interactions across the distinct tissue regions could provide greater insight into the role individual immune populations have within tumors.
Methods: A 39-parameter imaging mass cytometry panel was optimized with markers targeting immune cells, stromal cells, endothelial cells, hepatocytes, and tumor cells.
Front Immunol
January 2025
Amgen Research, Amgen Inc., South San Francisco, CA, United States.
Tolerogenic vaccines represent a therapeutic approach to induce antigen-specific immune tolerance to disease-relevant antigens. As general immunosuppression comes with significant side effects, including heightened risk of infections and reduced anti-tumor immunity, antigen-specific tolerance by vaccination would be game changing in the treatment of immunological conditions such as autoimmunity, anti-drug antibody responses, transplantation rejection, and hypersensitivity. Tolerogenic vaccines induce antigen-specific tolerance by promoting tolerogenic antigen presenting cells, regulatory T cells, and regulatory B cells, or by suppressing or depleting antigen-specific pathogenic T and B cells.
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