Coagulation factor VIIa enhances programmed death-ligand 1 expression and its stability in breast cancer cells to promote breast cancer immune evasion

Coagulation Protease-Driven Cancer Immune Evasion: Potential Targets for Cancer Immunotherapy

“…The treatment of cells with PAR2 activation peptide shows a similar induction of PD-L1 expression to that of FVIIa and PAR2 knock-down, which significantly down-regulates FVIIa-driven PD-L1 expression [136]. Mechanistically, the authors indicate that TF/FVIIa/PAR2 signaling triggers the inactivation of LATS1, thereby resulting in the loss of YAP/TAZ phosphorylation, leading to their subsequent localization into the nucleus [136]. The Knock-down of PAR2 or blocking cell surface TF dramatically reduced FVIIa-mediated LATS1 inactivation and the nuclear translocation of YAP/TAZ [136].…”

“…Although the role of FVIIa is well established in cancer growth and metastasis, its contribution to cancer immune evasion remains understudied. In a recent study, Paul et al, for the first time, showed that the TF/FVIIa-dependent activation of PAR2 triggers the immune evasion of breast cancer via the induction of programmed death-ligand 1 (PD-L1) expression and its stability [136]. PD-L1 is shown to be expressed in various cancer cells, and its receptor, PD-1, is found in the tumor-infiltrating lymphocytes.…”

“…In their study, Paul et al demonstrated that the TF/FVIIa-mediated activation of PAR2 promotes the expression of PD-L1 in human triple-negative breast cancer (TNBC) cells, leading to a down-regulation of CD8 + T-cell activity [136]. The treatment of cells with PAR2 activation peptide shows a similar induction of PD-L1 expression to that of FVIIa and PAR2 knockdown, which significantly down-regulates FVIIa-driven PD-L1 expression [136]. Mechanistically, the authors indicate that TF/FVIIa/PAR2 signaling triggers the inactivation of LATS1, thereby resulting in the loss of YAP/TAZ phosphorylation, leading to their subsequent localization into the nucleus [136].…”

“…The interaction of PD-L1/PD-1 not only triggers the down-regulation of lymphocyte proliferation but also induces lymphocyte apoptosis, leading to tumor immune evasion [137,138]. In their study, Paul et al demonstrated that the TF/FVIIa-mediated activation of PAR2 promotes the expression of PD-L1 in human triple-negative breast cancer (TNBC) cells, leading to a downregulation of CD8 + T-cell activity [136]. The treatment of cells with PAR2 activation peptide shows a similar induction of PD-L1 expression to that of FVIIa and PAR2 knock-down, which significantly down-regulates FVIIa-driven PD-L1 expression [136].…”

Potential Roles and Future Perspectives of Chitinase 3-like 1 in Macrophage Polarization and the Development of Diseases

“…Breast cancer, as the most common malignant tumor in women, has been studied by researchers from different fields regarding its pathogenesis. The complex interactions between breast cancer cells and immune cells of the adaptive and innate immune systems play a central role in tumor growth, metastasis, and treatment throughout the entire course of the disease [33,138]. In breast cancer progression, serum CHI3L1 levels are closely related to the degree of malignancy of breast cancer, and TAMs also play an important role.…”