Characterization of T cell repertoire of blood, tumor, and ascites in ovarian cancer patients using next generation sequencing

Tumor-infiltrating lymphocytes (TILs) play an important role in regulating the host immune response and are one of key factors in defining tumor microenvironment. Some studies have indicated that T cell infiltration in malignant ascites is associated with clinical outcome, but few studies have performed detailed characterization of T cell diversity or clonality in malignant effusions. We have applied a next generation sequencing method to characterize T cell repertoire of a set of primary cancers, ascites, and blood from 12 ovarian cancer patients and also analyzed the T cell subtype populations in malignant fluids from 3 ovarian cancer patients. We observed enrichment of certain T cells in tumors and ascites, but most of the enriched T cell receptor (TCR) sequences in tumors and ascites were not common. Moreover, we analyzed TCR sequences of T cell subtypes (CD4⁺, CD8⁺, and regulatory T cells) isolated from malignant effusions and also found clonal expansion of certain T cell populations, but the TCR sequences were almost mutually exclusive among the three subgroups. Although functional studies of clonally expanded T cell populations are definitely required, our approach offers a detailed characterization of T cell immune microenvironment in tumors and ascites that might differently affect antitumor immune response.