*3.2.2 Macrophages and immune cells*

Tumor MVs extravasate through the vessel wall in pancreatic cancer, reach the liver microcirculation and are picked up by perivascular macrophages to prime the liver metastatic niche in a CD36-dependent manner. Furthermore, tumor MVs produced from the B16F10 melanoma cell line was discovered to cause metastases in BALB/c mice, which are generally resistant to the B1610 tumor cell line [27]. TDEs also protect cancer cells from apoptosis by selectively effluxing apoptosis inducer proteins that are delivered by T cells or natural killer (NK) cells. TDEs also reduce the effects of therapy by preventing drug efflux or concealing the binding site of monoclonal antibodies, which could lead to the emergence of chemotherapy-resistant cell populations [28].

Exosome-derived programmed death receptor 1 (PD-1) and programmed deathligand 1 have been linked to an immunological escape mechanism in recent years. PD-1 is mostly found on macrophages, activated T cells, and B cells, whereas PD-L1 is abundant in tumor tissues, antigen-presenting cells (APCs), and stromal cells [29]. T lymphocytes can recognize and destroy tumor cells in normal circumstances. When PD-1 attaches to PD-L1, however, it sends an inhibitory signal to T cells, causing them to die

and inhibiting their activation and proliferation. As a result, blocking the PD-1/PD-L1 pathway may boost the immune response by increasing the killing effect of T cells [30]. T lymphocytes can recognize and destroy tumor cells in normal circumstances. When PD-1 attaches to PD-L1, however, it sends an inhibitory signal to T cells, causing them to die and inhibiting their activation and proliferation (**Figure 1**). As a result, blocking the PD-1/PD-L1 pathway may boost the immune response by increasing the killing effect of T cells. As a result, Exo containing PD-L1 suppress the immune system in the pre-metastatic milieu and promote the establishment of a pre-metastatic niche [31].
