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Proinflammatory allogeneic dendritic cells enhance the therapeutic efficacy of systemic anti-4-1BB treatment.
- Source :
- Frontiers in Immunology; 2023, p1-11, 11p
- Publication Year :
- 2023
-
Abstract
- As an immune adjuvant, proinflammatory allogeneic dendritic cells (AlloDCs) have demonstrated promising immune-priming effects in several preclinical and clinical studies. The effector cells, including NK cells and T cells are widely acknowledged as pivotal factors in the effectiveness of cancer immunotherapy due to their ability to selectively identify and eradicate malignant cells. 4-1BB, as a costimulatory receptor, plays a significant role in the stimulation of effector cell activation. This study evaluated the anti-tumor effects when combining intratumoral administration of the immune-adjuvant AlloDCs with systemic a4-1BB treatment directly acting on effector cells. In both the CT-26 murine colon carcinoma model and B16 murine melanoma model, AlloDCs demonstrated a significant enhancement in the therapeutic efficacy of α4-1BB antibody. This enhancement was observed through the delayed growth of tumors and prolonged survival. Analysis of the tumor microenvironment (TME) in the combined-treatment group revealed an immune-inflamed TME characterized by increased infiltration of activated endogenous DCs and IFNg+ CD8<superscript>+</superscript> T cells, showing reduced signs of exhaustion. Furthermore, there was an augmented presence of tissue-resident memory (TRM) CD8<superscript>+</superscript> T cells (CD103<superscript>+</superscript>CD49a<superscript>+</superscript>CD69<superscript>+</superscript>). The combination treatment also led to increased infiltration of CD39<superscript>+</superscript>CD103<superscript>+</superscript> tumor-specific CD8<superscript>+</superscript> T cells and neoantigenspecific T cells into the tumor. Additionally, the combined treatment resulted in a less immunosuppressive TME, indicated by decreased infiltration of myeloidderived suppressor cells and Tregs. These findings suggest that the combination of intratumoral AlloDCs administration with systemic agonistic α4-1BB treatment can generate a synergistic anti-tumor response, thereby warranting further investigation through clinical studies. [ABSTRACT FROM AUTHOR]
- Subjects :
- DENDRITIC cells
SUPPRESSOR cells
TREATMENT effectiveness
KILLER cells
CANCER cells
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Database :
- Complementary Index
- Journal :
- Frontiers in Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 171295662
- Full Text :
- https://doi.org/10.3389/fimmu.2023.1146413