Abstract
The immuno-inhibitory checkpoint PD-L1, regulated by tumor cells and antigen-presenting cells (APCs), dampened the activation of T cells from the PD-1/PD-L1 axis. PD-L1-expressing APCs rather than tumor cells demonstrated the essential anti-tumor effects of anti-PD-L1 monotherapy in preclinical tumor models. Using the murine tumor model, we investigated whether anti-PD-L1 antibody increased the antigen-specific immune response and anti-tumor effects induced by the antigen-specific protein vaccine, as well as the possible mechanisms regarding activation of APCs. Anti-PD-L1 antibody combined with the PEK protein vaccine generated more potent E7-specific immunity (including the number and cytotoxic activity of E7-specific cytotoxic CD8+ T lymphocytes) and anti-tumor effects than protein vaccine alone. Anti-PD-L1 antibody enhanced the maturation of dendritic cells and the proportion of M1-like macrophages in tumor-draining lymph nodes and tumors in tumor-bearing mice treated with combinatorial therapy. PD-L1 blockade overturned the immunosuppressive status of the tumor microenvironment and then enhanced the E7 tumor-specific antigen-specific immunity and anti-tumor effects generated by an E7-specific protein vaccine through modulation of APCs in an E7-expressing small tumor model. Tumor-specific antigen (like HPV E7 antigen)-specific immunotherapy combined with APC-targeting modality by PD-L1 blockade has a high translational potential in E7-specific cancer therapy.
Highlights
Cancer cells have developed several strategies to escape from immune surveillance, such as loss of antigenicity, loss of immunogenicity, and development of an immunosuppressive microenvironment [1].Loss of immunogenicity, including the expression of programmed death-ligand 1 (PD-L1) on tumor cells, plays a crucial role in tumor evasion of host immune responses [2]
We investigated whether other cell types, such as bone marrow monocyte (BMM)-derived dendritic cells (DCs) and macrophages, expressed PD-L1
T Cellsof the present study revealed that PD-L1 blockade enhanced the antigen-specific anti-tumor effects and cell-mediated immunities of an antigen-specific protein vaccine beyond those of Representative figures depicting the flow cytometric analysis for E7-specific IFN-γ-secreting the protein vaccine alone
Summary
Cancer cells have developed several strategies to escape from immune surveillance, such as loss of antigenicity, loss of immunogenicity, and development of an immunosuppressive microenvironment [1].Loss of immunogenicity, including the expression of programmed death-ligand 1 (PD-L1) on tumor cells, plays a crucial role in tumor evasion of host immune responses [2]. Interaction between programmed death-1 (PD-1) receptor and its ligands PD-L1 and PD-L2 leads to inhibition of the proliferation, cytokine secretion, and cytotoxic activity of T cells [3,4]. When PD-1 expression on T cells binding with PD-L1 and/or PD-L2 expression on APCs occurs, PD-1 inhibits T cell activation by recruiting tyrosine phosphatase SHP2, which directly attenuates TCR signaling through dephosphorylation [5]. Blockade of the PD-1/PD-L1 signaling pathway by anti-PD-1 or anti-PD-L1 immune checkpoint antibody therapy has produced unprecedented and durable responses in the treatment of melanoma and lung cancer patients [7]. PD-L1 expressed on tumor cells as a biomarker can predict the responses of cancer patients treated with anti-PD-L1 antibody therapy, and increased PD-L1 expression on tumor cells is associated with better anti-tumor immunity after
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
