Radiation and anti-PD-L1 antibody combinatorial therapy induces T cell-mediated depletion of myeloid-derived suppressor cells and tumor regression
نویسندگان
چکیده
Tumor relapse after radiotherapy may be due to the upregulation of programmed cell death ligand 1 (PD-L1). We demonstrated that anti-PD-L1 antibody synergizes with radiation to control local and distal tumors. CD8+T cells mediated antitumor effects of the combination therapy by the reduction of myeloid-derived suppressor cells (MDSCs) via tumor-necrosis factor (TNF)-mediated signaling. Our study provides insight into immune- and radiation-based combinational therapies.
منابع مشابه
Multiple Low Doses of 5-Fluorouracil Diminishes Immunosuppression by Myeloid Derived Suppressor Cells in Murine Melanoma Model
Background: Melanoma progression and metastasis is suggested to be mediated by increased accumulation of myeloid derived suppressor cells. Various chemotherapeutic drugs such as 5-Fluorouracil in single low concentration have the capacity, at least in part, to reverse tumor progression by reducing myeloid derived suppressor cellsmediated immunosuppression. Objective: To assess whether multiple ...
متن کاملIrradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice.
High-dose ionizing irradiation (IR) results in direct tumor cell death and augments tumor-specific immunity, which enhances tumor control both locally and distantly. Unfortunately, local relapses often occur following IR treatment, indicating that IR-induced responses are inadequate to maintain antitumor immunity. Therapeutic blockade of the T cell negative regulator programmed death-ligand 1 (...
متن کاملAnti-PD-1 antibody significantly increases therapeutic efficacy of Listeria monocytogenes (Lm)-LLO immunotherapy
BACKGROUND One of the significant tumor immune escape mechanisms and substantial barrier for successful immunotherapy is tumor-mediated inhibition of immune response through cell-to-cell or receptor/ligand interactions. Programmed death receptor-1 (PD-1) interaction with its ligands, PD-L1 and PD-L2, is one of the important strategies that many tumors employ to escape immune surveillance. Upon ...
متن کاملTherapeutic PD-1 pathway blockade augments with other modalities of immunotherapy T-cell function to prevent immune decline in ovarian cancer.
The tumor microenvironment mediates induction of the immunosuppressive programmed cell death-1 (PD-1) pathway, and targeted interventions against this pathway can help restore antitumor immunity. To gain insight into these responses, we studied the interaction between PD-1 expressed on T cells and its ligands (PD-1:PD-L1, PD-1:PD-L2, and PD-L1:B7.1), expressed on other cells in the tumor microe...
متن کاملAnti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells.
PURPOSE To determine the antitumor efficacy and toxicity of a novel combination approach involving adoptive T-cell immunotherapy using chimeric antigen receptor (CAR) T cells with an immunomodulatory reagent for blocking immunosuppression. EXPERIMENTAL DESIGN We examined whether administration of a PD-1 blocking antibody could increase the therapeutic activity of CAR T cells against two diffe...
متن کامل