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

Abstract

ProblemWe 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 studyT 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.ResultsWe 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.ConclusionThe identified immune clusters serve as the basis for interrogation of the peritoneal immune environment and the development of novel immunologic modalities against ovarian cancer.

Malignant Ascites in Ovarian Cancer: Cellular, Acellular, and Biophysical Determinants of Molecular Characteristics and Therapy Response

“…In one study, a higher proportion of CD8+ T c (median 51.6%) was observed in tumor-infiltrating lymphocytes relative to peripheral blood leukocytes (23.9%), while ascites samples contained similar proportions of CD4+ T h and CD8+ T c (46.5% and 44.5%, respectively) [191]. Another study examining T cell diversity in the ascites of HGSOC patients compared to peripheral blood of post-menopausal healthy donors found that 3/15 patients had very low levels of CD3+ T cells, while the relative abundance of CD3+ T cells ranged from 25%-42% of total live CD45+ immune cells in 8/15 patients [192]. Additionally, flow cytometry data showed that HGSOC ascites contained a high proportion of activated CD4+ and effector memory T cells (CD4+ and CD8+) [192].…”

“…Further analysis examining dendritic cell presence and distribution found that DC presence increased in HGSOC ascites and that plasmacytoid DCs were the most represented subtype [192]. Additionally, when examining innate lymphoid cell (ILC) presence in HGSOC ascites, NK cells were found in higher proportion compared to ILC3s and lymphoid tissue inducer-like cells [192]. Specifically, Vazquez et al [192] found a significant increase in the proportion of CD56 bright NK cells, which are compromised in cytolyzing cancer targets yet efficient at producing cytokines.…”

“…Additionally, flow cytometry data showed that HGSOC ascites contained a high proportion of activated CD4+ and effector memory T cells (CD4+ and CD8+) [192]. Further analysis examining dendritic cell presence and distribution found that DC presence increased in HGSOC ascites and that plasmacytoid DCs were the most represented subtype [192]. Additionally, when examining innate lymphoid cell (ILC) presence in HGSOC ascites, NK cells were found in higher proportion compared to ILC3s and lymphoid tissue inducer-like cells [192].…”

“…Another study examining T cell diversity in the ascites of HGSOC patients compared to peripheral blood of post-menopausal healthy donors found that 3/15 patients had very low levels of CD3+ T cells, while the relative abundance of CD3+ T cells ranged from 25%-42% of total live CD45+ immune cells in 8/15 patients [192]. Additionally, flow cytometry data showed that HGSOC ascites contained a high proportion of activated CD4+ and effector memory T cells (CD4+ and CD8+) [192]. Further analysis examining dendritic cell presence and distribution found that DC presence increased in HGSOC ascites and that plasmacytoid DCs were the most represented subtype [192].…”

Dendritic Cell Vaccines in Ovarian Cancer

“…The ratio of cDC and pDC varies between peripheral blood, ascites and tumor sites. According to The most prominent subsets of DCs is pDC in ascites ( 50 ) and tumor sites ( 34 ), while cDC is more than pDC in the peripheral blood ( 35 ), which suggests that peripheral blood could be a proper resource of the DCs for manufacturing.…”