Identification of unique clusters of T, dendritic, and innate lymphoid cells in the peritoneal fluid of ovarian cancer patients

Problem: We hypothesize that activated peritoneal immune cells can be redirected to target ovarian tumors. Here, we obtain fundamental knowledge of the peritoneal immune environment through deep immunophenotyping of T cells, dendritic cells (DC), and innate lymphoid cells (ILC) of ovarian cancer patients.

Method of study: T cells, DC, and ILC from ascites of ovarian cancer patients (n = 15) and peripheral blood of post-menopausal healthy donors (n = 6) were immunophenotyped on a BD Fortessa cytometer using three panels-each composed of 16 antibodies. The data were analyzed manually and by t-SNE/DensVM. CA125 levels were obtained from patient charts.

Results: We observed decreased CD3⁺ T cells and a higher proportion of activated CD4⁺ and effector memory CD4⁺ /CD8⁺ T cells, plasmacytoid DC, CD1c⁺ and CD141⁺ myeloid DC and CD56^Hi NK cells in ascites. t-SNE/DensVM identified eight T cell, 17 DC, and 17 ILC clusters that were unique in the ascites compared to controls. Hierarchical clustering of cell frequency distinctly segregated the T-cell and ILC clusters from controls. Increased CA125 levels were associated with decreased CD8⁺ /CD45RA⁺ /CD45RO^- /CCR7^- T cells.

Conclusion: The identified immune clusters serve as the basis for interrogation of the peritoneal immune environment and the development of novel immunologic modalities against ovarian cancer.