title: Characterization of T cell repertoire of blood, tumor, and ascites in ovarian cancer patients using next generation sequencing.
abstract: 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.
authors.affiliation: Department of Medicine; The University of Chicago ; Chicago, IL USA.
authors.forename: Miran
authors.initials: M
authors.lastname: Jang
authors.affiliation: Department of Medicine; The University of Chicago ; Chicago, IL USA.
authors.forename: Poh-Yin
authors.initials: PY
authors.lastname: Yew
authors.affiliation: Department of Gynecologic Oncology; Saitama Medical University International Medical Center ; Hidaka, Saitama, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Department of Medicine; The University of Chicago ; Chicago, IL USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Department of Gynecologic Oncology; Saitama Medical University International Medical Center ; Hidaka, Saitama, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Department of Medicine; The University of Chicago ; Chicago, IL USA.
authors.forename: Gini F
authors.initials: GF
authors.lastname: Fleming
authors.affiliation: Department of Medicine; The University of Chicago ; Chicago, IL USA ; Department of Surgery; The University of Chicago ; Chicago, IL USA.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Medicine; The University of Chicago ; Chicago, IL USA.
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Park
keywords: T cell receptor; malignant ascites; next generation sequencing; ovarian cancer; tumor immunity