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 C , CD8 C , 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.

T‐cell receptor diversity as a prognostic biomarker in melanoma patients

“…In HCC patients, the T‐cell repertoires in tumor and matched adjacent non‐tumor tissues were found to be different (Chen et al, ), suggesting a distinct T‐cell immune microenvironment. Furthermore, in ovarian cancer patients T‐cell repertoire in tumors and ascites was found to be different (Jang et al, ). The T‐cell repertoire in blood and tumor of patients with advanced colorectal cancer were found to be entirely distinct (Tamura et al, ).…”

TCR sequencing analysis of cancer tissues and tumor draining lymph nodes in colorectal cancer patients

“…We established next-generation sequencing-based TCR repertoire analysis using mRNAs and applied our technology for the TCR analysis of various types of tumor. [15][16][17][18][19][20][21] A detailed TCR transcript analysis has provided a new insight into T cell responses in various disease conditions including characterization of the tumor microenvironment.…”

Identification of shared TCR sequences from T cells in human breast cancer using emulsion RT-PCR

“…The alpha-and beta-chains of the TCR undergo V(D)J recombination and heterodimerize in the thymus, resulting in a diverse T-cell repertoire that specifically recognizes peptide-MHC complexes. Many studies have analyzed the alpha-and beta-chains of TIL TCRs separately using highthroughput sequencing to describe the diversity of TILs (10)(11)(12)(13). Pairs are readily identified after expansion of T-cell clones, although culture of T cells can lead to substantial skewing of the repertoire (14), which may select for T cells of varied affinity or avidity (15).…”