Interestingly, the combination treatment of VPA and anti-PD-L1 antibody activated IRF1/IRF8 transcriptional axis in MDSCs leading to blockade of their immunosuppressive function by downregulating the expression of IL-10, IL-6, and ARG1 while re-activating CD8<sup>+</sup> T-cells for the production of TNFα to further enhance anti-tumor immunity.
Collectively, our study identifies DCLK1 as an important regulator of PD-L1 expression in pancreatic tumor and highlights a central role of DCLK1 in the regulation of tumor immunity.
We postulate that ADAM10 and/or ADAM17 may contribute to the regulation of the PD-L1/PD-1 pathway and, ultimately, to anti-tumor immunity in triple-negative breast cancer.
We summarize the current state of knowledge about ICOS/ICOSL pathway targeting by immunotherapies.<b>Expert opinion</b>: Due to its multifaceted link with anti-tumor immunity, both antagonist and agonist antibodies might be of interest to target the ICOS/ICOSL pathway for tumor treatment.
We place particular focus on TAM receptors and the recently unraveled role of MERTK in activated T cells and potential consequences for anti-tumor immunity.
We postulate that ADAM10 and/or ADAM17 may contribute to the regulation of the PD-L1/PD-1 pathway and, ultimately, to anti-tumor immunity in triple-negative breast cancer.
In addition, HDAC6 inhibition enhances tumor immunity and has been suggested to strengthen the cytotoxic effects of therapeutic antibodies against myeloma.
The selected DEGs, including interleukin-10, beta-2 microglobulin, C-C motif chemokine ligand 5, cluster of differentiation 74, human leukocyte antigen-DRA, lymphocyte cytosolic protein 2, and myxovirus resistance protein 1, associated with tumor immunity and microenvironment, have prognostic values in grade II/III glioma.
In contrast with this positive regulation of TAM recruitment, we found no evidence of a direct effect of ERK1/2 signaling on two other important aspects of TAM regulation by GBM cells: (1) the expression of the immune checkpoint ligands PD-L1 and PD-L2, expressed at high mRNA levels in GBM compared with other solid tumors; (2) the production of the tumor metabolite lactate recently reported to dampen tumor immunity by interacting with the receptor GPR65 present on the surface of TAM.
Another novel cancer vaccine approach is to stimulate anti-tumor immunity via STING activation in Batf3-dependent dendritic cells (DC) through the use of replication-attenuated VV vectors.
Our results reveal previously unappreciated cooperative roles for T<sub>reg</sub> cell-derived IL-10 and IL-35 in promoting BLIMP1-dependent exhaustion of CD8<sup>+</sup> TILs that limits effective anti-tumor immunity.
We previously demonstrated that the Fap2 outer-surface protein of <i>F. nucleatum</i> binds and activates the human inhibitory receptor TIGIT which is expressed by T and Natural Killer (NK) cells, and inhibits anti-tumor immunity.Here we show that <i>F. nucleatum</i> also binds and activates the human inhibitory receptor CEACAM1 leading to inhibition of T and NK cells activities.
Here, we found that TRAF6-deficient Tregs were dysfunctional <i>in vivo</i>; mice with Treg-restricted deletion of TRAF6 were resistant to implanted tumors and displayed enhanced anti-tumor immunity.
We demonstrate in models of ovarian cancer, melanoma, and glioblastoma that infusions of nanoparticles formulated with mRNAs encoding interferon regulatory factor 5 in combination with its activating kinase IKKβ reverse the immunosuppressive, tumor-supporting state of TAMs and reprogram them to a phenotype that induces anti-tumor immunity and promotes tumor regression.