Anti-CD80 polyclonal antibody [Biotin]

The expression of PD-L1 on tumor cells or within the tumor microenvironment has been associated with good prognosis and sustained clinical responses in immunotherapeutic regimens based on PD-L1/PD-1/CD80 immune checkpoint blockade. To look into the current controversy in cancer immunotherapy of the relative importance of PD-L1 expression on tumor cells versus non-tumor cells of the tumor microenvironment, a hematological mouse tumor model was chosen. By combining a genetic CRISPR/Cas9 and immunotherapeutic approach and using a syngeneic hematopoietic transplantable tumor model (E.G7-cOVA tumor cells), we demonstrated that dual blockade of PD-L1 interaction with PD-1 and CD80 enhanced anti-tumor immune responses that either delayed tumor growth or led to its complete eradication. PD-L1 expression on non-tumor cells of the tumor microenvironment was required for the promotion of tumor immune escape and its blockade elicited potent anti-tumor responses to PD-L1 WT and to PD-L1-deficient tumor cells. PD-L1(+) tumors implanted in PD-L1-deficient mice exhibited delayed tumor growth independently of PD-L1 blockade. These findings emphasize that PD-L1 expression on non-tumor cells plays a major role in this tumor model. These observations should turn our attention to the tumor microenvironment in hematological malignancies because of its unappreciated contribution to create a conditioned niche for the tumor to grow and evade the anti-tumor immune response.

The embryo is a natural allograft and is the only exception to immune rejection, which reflects maternal immune tolerance towards the embryo. However, pregnancy loss is primarily caused by maternal immune rejection of the embryo. The aim of the present study was to explore the effects of combined treatment of programmed death-ligand 1 (PD-L1) immunoglobulin (Ig) and CD40-ligand (CD40L) monoclonal antibody (mAb) on immune tolerance in an abortion-prone mating model. Mice were divided into the normal, spontaneous abortion, PD-L1 Ig, CD40L mAb and the PD-L1 Ig + CD40L mAb groups. On day 14 of gestation, the embryo resorption abortion rates of all the groups was observed. The maternal hypo-responsiveness to paternal antigens was determined using a mixed lymphocyte response and the splenic CD4(+)CD25(+) T-cell population, major histocompatibility complex (MHC)-II+, CD80(+) and CD86(+) cell populations in pregnant female CBA/J mice were analyzed using flow cytometry. The expression levels of intracellular cytokines in the splenic tissues of pregnant CBA/J female mice were analyzed using western blotting. The PD-L1 Ig + CD40L group displayed the lowest resorption rate compared with the other groups. A significant decrease in the proliferative response of maternal splenic immunocompetent cells against paternal antigens, and a significant increase in the proliferative response of maternal splenic CD4(+)CD25(+) T cells was observed in the PD-L1 Ig + CD40L group compared with the spontaneous abortion group. The number of MHC-II+, CD80(+) and CD86(+) bone marrow-derived dendritic cells (DCs) generated by female mice, and the levels of tumor necrosis factor-alpha and interferon-gamma in the spleens of female mice were significantly decreased in the PD-L1 Ig + CD40L mAb group compared with the spontaneous abortion group. By contrast, interleukin-4 levels were significantly increased in the PD-L1 Ig + CD40L mAb group compared with the spontaneous abortion group. The results suggested that the administration of PD-L1 Ig + CD40L mAb on day 4 of gestation, the period of peri-implantation, may induce paternal antigen-specific immunotolerance, leading to the embryo resorption rate of the abortion-prone model being similar to that of the normal pregnancy model. The results indicate that the combined treatment of PD-L1 Ig and anti-CD40L mAbs may serve as a potential therapeutic for pregnancy loss.