T follicular helper cell changes after immune checkpoint inhibitor treatment in melanoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08779
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Kato Junji 札幌医科大学, 医学部, 助教 (00464488)
• Co-Investigator(Kenkyū-buntansha): 亀倉 隆太 札幌医科大学, 医学部, 講師 (70404697)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: Tfh細胞 / 免疫チェックポイント阻害薬 / 悪性黒色腫

Outline of Final Research Achievements

T follicular helper (Tfh) cells are a subset of CD4+ T cells that regulate mainly antibody production by B cells in the follicular center. The proliferation of circulating Tfh (cTfh) cells is observed in autoimmune diseases including rheumatoid arthritis and immunoglobulin G4 (IgG4)-related diseases. Immune checkpoint inhibitors (ICIs) induce various autoimmune adverse events, but the underlying mechanism is not fully understood. We examined the changes of cTfh cells, the activated cTfh ([ICOS]+ cTfh cells), and circulating Tfr (cTfr, Foxp3+ cTfh) cells including their relationships with the clinical response and immune-related adverse events (irAEs) in ICI treatment.The cTfh cells did not change after ICI treatment (p=0.476) in any patient, whereas the activated cTfh cells were significantly increased after ICI treatments in four patients who achieved a clinical response or exhibited serious irAEs compared to the other patients.

Free Research Field

皮膚がん

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害薬(ICI)の効果や副作用にはCD8+T細胞が重要であるが、CD4+T細胞の関連性は未だ不明なことが多い。今回の研究は免疫チェックポイント阻害薬投与前および投与中の末梢血を用いてCD4+T細胞のなか濾胞性ヘルパーT　(Tfh)　細胞に注目して研究を行った。研究でTfh細胞の活性化が免疫チェックポイント阻害薬投与後におこった患者で、免疫が動く（効果や副作用がみられる）ことが観察できた。
Tfh細胞の活性化は投与後早期（2週間後）に観察されることがわかった。そのため, 活性化がおこるかどうかの評価は治療前と投与後約2週間後のツーポイントでに行うことで評価ができそうと考えた。