Highly clonal regulatory T-cell population in follicular lymphoma – inverse correlation with the diversity of CD8⁺T cells

Abstract

The immune microenvironment in follicular lymphoma (FL) plays an important role in controlling disease characteristics. To characterize the T-cell receptor (TCR) repertoire in follicular lymphoma (FL) tissues, we applied a nextgeneration sequencing platform and deeply sequenced TCR cDNAs of T-cell subset populations present in pretreatment FL biopsy specimens. T regulatory cell (T reg ) TCRs in FL tissues revealed a highly oligoclonal expansion compared to those in control lymph nodes. Furthermore, an inverse correlation was observed between the diversity of T reg and CD8 + TCRs in FL specimens. Interestingly, a tumor from an FL patient, who had not received anticancer treatment for more than 10 years, was found to have missense mutations in the peptide-binding domain of both human leukocyte antigen (HLA) class I and II molecules, which might have presented tumor-specific antigens and enhanced host immune responses. Although further verification is required, our data suggest that the T-cell repertoire is skewed and restricted in FL and support the evolving understanding of the microenvironment in this disease.

Potential targeting of B7‐H4 for the treatment of cancer

“…Treg cells can accumulate in both the peripheral blood and the cancer microenvironment and have been shown to expand during cancer progression suggesting that Treg cells may play a pivotal role in suppressing anti‐tumor immunity . In support of this hypothesis, Treg cell depletion or functional suppression results in augmented T‐cell immune responses against cancer in both mice and humans . As an additional link between B7‐H4 and Treg cells, a study using human cervical carcinoma found that B7‐H4 promoted the growth of Treg cells .…”

“…100 In support of this hypothesis, Treg cell depletion or functional suppression results in augmented T-cell immune responses against cancer in both mice and humans. 101 As an additional link between B7-H4 and Treg cells, a study using human cervical carcinoma found that B7-H4 promoted the growth of Treg cells. 99 Another study demonstrated that B7-H4 promoted cancer tolerance and may contribute to Treg cell development in colorectal cancer.…”

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.…”

Losses of cytokines and chemokines are common genetic features of human cancers: the somatic copy number alterations are correlated with patient prognoses and therapeutic resistance

“…Several studies have revealed the prognostic impact of infiltrating immune cells. 38,39 Arnold Han et al 40 , X. Liu et al 41 and M. Jang et al 42 have characterized the immune repertoire profiles of T cells in colorectal carcinoma, follicular lymphoma and ovarian cancer, respectively. Their studies suggested a profound enrichment of specific T-cell receptor clones in local cancer sites.…”