The comprehensive assessment of local immune status of ovarian cancer by the clustering of multiple immune factors

Abstract

The aim of this study was to evaluate the local immune status of human ovarian cancers by the comprehensive analysis of tumor-infiltrating immune cells and immunosuppressive factors, and to elucidate the local immunity in clinical course. The numbers of CD1α+, CD4+, CD8+, CD57+, forkhead box P3+ and programmed cell death-1+ cells were counted, and the intensity of immunosuppressive factors, such as programmed cell death-1 ligand (PD-L)1, PD-L2, cyclooxygenase (COX)-1, COX-2 and transforming growth factor β1, were evaluated in 70 ovarian cancer specimens stained by immunohistochemistry. Then hierarchical clustering of these parameters showed the four clusters into ovarian cancer cases. Cluster 1, which had significantly better prognosis than the others, was characterized by high infiltration of CD4+ and CD8+ cells. In conclusion the comprehensive analysis of local immune status led to subdivide ovarian cancers into groups with better or worse prognoses and may guide precise understanding of the local immunity.

PD-L1 on Tumor Cells Is Induced in Ascites and Promotes Peritoneal Dissemination of Ovarian Cancer through CTL Dysfunction

“…By binding to its receptor PD-1 on lymphocytes, it generates an inhibitory signal toward the T-cell receptor (TCR)-mediated activation of lymphocytes (19,20). We have reported that PD-L1 expression in tumor cells is an independent unfavorable prognostic factor in human ovarian cancer (15), and that PD-L1 expression showed the closest relation to unfavorable prognosis among other immunosuppressive molecules that we have tested (18). These data suggest that PD-L1 has a role in the clinical course of ovarian cancer by affecting the local immune microenvironment and that PD-L1/PD-1 signal could be a potential therapeutic target.…”

“…Immunohistochemical staining for PD-L1 was conducted using a PD-L1 antibody as previously described (15,18). PD-L1 expression was analyzed by 2…”

“…Restoring immune function in cancer microenvironment has immense potential for a new cancer therapy (14). We have attempted to elucidate the mechanism of immune escape in ovarian cancer and reported that in the ovarian cancer microenvironment, molecules such as ULBP2 (NKG2D ligand), COX-1, COX-2, and programmed cell death 1 ligand 1 (PD-L1) or the combined expression of these molecules are related to limited infiltration by lymphocytes and an unfavorable prognosis (15)(16)(17)(18). PD-L1 (also known as B7-H1 or CD274) is a coregulatory molecule that is expressed on the surface of various types of cells, including immune cells and epithelial cells.…”

Immunotherapy against endocrine malignancies: immune checkpoint inhibitors lead the way

“…This supports the idea that complex crosstalk between tumor-infiltrating lymphocytes and ovarian tumor cells may mediate the PD-1/PD-L1 axis activation. It is not surprising that patients with ovarian cancer who were stratified based on high levels of tumor-infiltrating lymphocytes (tumors enriched with CD4+, CD8+ and PD-1+ cells) and low expression of immune regulatory molecules (TGFB1, PD-L1, PD-L2, COX-1 and COX-2) had significantly better prognosis than patients in the other groups (Hamanishi et al 2011). Taken together, the preclinical results led scientists to pursue the blockage of the PD-1/PD-L1 axis as a therapy for patients with ovarian cancer.…”

Tumor infiltrating lymphocytes in ovarian cancer

“…17 Similar results have been reported extensively elsewhere. [18][19][20][21][22][23][24][25][26][27][28][29][30][31] Three other studies indicate that both CD3 and CD8C TILs are of good prognosis in ovarian cancer. [32][33][34] While CD8C TILs appear to be best associated with improved survival, still other reports indicate that CD4C TILs are the subset of value in prognosticating ovarian cancer.…”