Abstract
Purpose: To study the role of programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) signaling pathway in patients with epithelial ovarian cancer (EOC). Methods: A total of 10 EOC specimens and 10 benign ovarian tumor were obtained from surgery and the pathological type. We used the methods of immunofluorescence confocal microscopy, western blot, MTT assay, apoptosis detection and co-culture to verify the aim of the research. Results: In the present study, it was validated that the number of PD-L1+ tumor-associated macrophages (TAMs) per field was significantly increased in EOC tissues compared with benign ovarian tumor tissues. Furthermore, it was demonstrated that PD-L1 was expressed on the membrane of TAM-derived exosomes, which may inhibit the proliferation and induce the apoptosis of T cells by activating the caspase 3 signaling pathway. The analysis of the supernatant of T cells co-cultured with TAM drived exosome revealed that the levels of pro-inflammatory cytokines and tumor necrosis factor α decreased compared with those T cells co-cultured with monocyte drived exosome. However, the expression of the immuno-suppressive cytokine, interleukin 10 and markers of T cell exhaustion (the inhibitory molecule lymphocyte activated gene-3, T-cell immunoglobulin and mucin domain-containing protein-3 and PD-1) increased. Conclusions: The present study demonstrated that the M2-derived exosomes regulate immune suppression in the EOC microenvironment. The findings of the present study provide a theoretical basis for future target therapy on exosomes from immune cells to treat EOC.
Mucinous borderline ovarian tumor versus invasive well-differentiated mucinous ovarian cancer: Difference in characteristics and outcomes
