Product Citations: 2

Immunological potential of tertiary lymphoid structures surrounding the primary tumor in gastric cancer.

In International Journal of Oncology on 1 July 2020 by Yamakoshi, Y., Tanaka, H., et al.

Tertiary lymphoid structures (TLSs), which consist of B cells, T cells, follicular dendritic cells and high endothelial venules, have recently been found to be associated with effective antitumor immune responses in patients with cancer. Tumor‑infiltrating T cells and B cells have each been demonstrated to be associated with survival in patients with cancer. We hypothesized that TLSs, an assembly of immune cells, may be important for the initiation and/or maintenance of T cell and B cell responses against tumors. The aim of the present study was to examine the cellular mechanism of B cells in TLSs within gastric cancer and to understand the antitumor immune response of TLSs. Each B cell subset in a tumor was examined using flow cytometry to evaluate B cell differentiation and the functional status of B cells. In addition, B cell clonality was investigated by analyzing the B cell antigen receptor gene using PCR, and the function and formation/maintenance of TLSs were evaluated using reverse transcription‑quantitative PCR. Tumor‑infiltrating B cells were more differentiated compared with that in distant non‑tumor tissues and tumor‑draining lymph nodes. The PCR results revealed specific BCR gene expression in tumor‑infiltrating B cells. The expression of co‑stimulatory factors, CD80 and CD86, was observed, in addition to the constantly expressed major histocompatibility complex molecules (HLA‑ABC and HLA‑DR). CD70 was expressed in addition to CD27 in both CD20+ B cells and CD8+ T cells, indicating that these factors are activated together through their interaction. The mRNA expression levels of CCL21, CXCL13, PD‑L1, perforin and granzyme B in TLSs was significantly higher compared with that in non‑TLSs. The majority of tumor‑infiltrating B cells in gastric cancer exist in the form of TLSs around the tumor and have been antigen‑sensitized and differentiated, and proliferated in TLSs but not in the lymph nodes. In addition, B cells in TLSs might primarily function as antigen‑presenting cells and be associated with the induction of cytotoxic T cells.

  • FC/FACS
  • Homo sapiens (Human)
  • Cancer Research
  • Immunology and Microbiology

Trace elements play important roles in human health, but little is known about their functions in humoral immunity. Here, we show an important role for iron in inducing cyclin E and B cell proliferation. We find that iron-deficient individuals exhibit a significantly reduced antibody response to the measles vaccine when compared to iron-normal controls. Mice with iron deficiency also exhibit attenuated T-dependent or T-independent antigen-specific antibody responses. We show that iron is essential for B cell proliferation; both iron deficiency and α-ketoglutarate inhibition could suppress cyclin E1 induction and S phase entry of B cells upon activation. Finally, we demonstrate that three demethylases, KDM2B, KDM3B and KDM4C, are responsible for histone 3 lysine 9 (H3K9) demethylation at the cyclin E1 promoter, cyclin E1 induction and B cell proliferation. Thus, our data reveal a crucial role of H3K9 demethylation in B cell proliferation, and the importance of iron in humoral immunity.

  • ELISA
  • Mus musculus (House mouse)
  • Genetics
  • Immunology and Microbiology
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