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

· 2020-06-30

Abstract

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 CD56Hi 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.

Funding

NICHD NIH HHS

K12 HD000849

NCI NIH HHS

P30 CA014520

NIGMS NIH HHS

R25 GM083252

NIH HHS

S10 OD018202

Burroughs Wellcome Fund

1019835

March of Dimes Foundation

5‐FY18‐541

Eunice Kennedy Shriver National Institute of Child Health and Human Development

5K 12HD000849‐28