Elucidation of the molecular basis of chemokine networks and identification of potential therapeutic targets in diffuse large B-cell lymphoma associated with chronic inflammation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08714
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kochi University
• Principal Investigator: Daibata Masanori 高知大学, 教育研究部医療学系基礎医学部門, 教授 (50263976)
• Co-Investigator(Kenkyū-buntansha): 樋口 智紀 高知大学, 教育研究部医療学系基礎医学部門, 講師 (00448771) ; 橋田 裕美子 高知大学, 教育研究部医療学系基礎医学部門, 助教 (00767999)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: リンパ腫 / ウイルス / ケモカイン / 慢性炎症

Outline of Final Research Achievements

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI) develops in the setting of long-standing inflammation. EBV-positive pyothorax-associated lymphoma (PAL) is a prototype of DLBCL-CI. Using a panel of PAL cell lines, we found that PAL cells expressed and secreted CXCL9 and CXCL10 chemokines, the ligands of CXCR3. Culture supernatants from PAL cell lines attracted CXCR3-expressing CD4-positive T cells, CD8-positive T cells, and CD56-positive natural killer cells from human peripheral blood mononuclear cells. PAL cells injected into mice also attracted CXCR3-positive cytotoxic lymphocytes that expressed interferon-gamma. The expression of CXCL9 and CXCL10 was detected in tumor biopsy samples from patients with PAL, and CXCR3-positive lymphocytes were abundant in the tissues. Collectively, these findings suggest that CXCL9 and CXCL10 are produced by PAL cells and can elicit cytotoxic responses via CXCR3.

Free Research Field

血液腫瘍学・ウイルス学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果は、PAL細胞がケモカインCXCL9とCXCL10を分泌することによりCXCR3を発現する腫瘍傷害性リンパ球を腫瘍部位に引き寄せることを示している。誘引された腫瘍傷害性リンパ球によってリンパ腫細胞を排除あるいはその進展を抑制できる可能性があり、このことを活用することにより慢性炎症に伴うびまん性大細胞型B細胞リンパ腫の新規治療法につながることが期待される。