Comprehensive search for HLA Class II-restricted peptides in breast cancer neoantigens

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08614
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: University of Tsukuba
• Principal Investigator: Bando Hiroko 筑波大学, 医学医療系, 准教授 (00400680)
• Co-Investigator(Kenkyū-buntansha): 宮寺 浩子 筑波大学, 医学医療系, 助教 (40361464)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Neoantigen / HLA / 乳癌 / T細胞エピトープ

Outline of Final Research Achievements

The importance of HLA class II and helper T cells in anti-tumor immunity has been well recognized, but not fully investigated whether there are neoantigens in hormone receptor positive (HR+) breast cancer with poor prognosis. To find a potential target neoantigens, we measured the interaction of HLA class II and public neoantigens commonly found in HR+ breast cancer. We selected frequent missense mutations in ESR1 and PIK3CA from the Catalogue of Somatic Mutations in Cancer (COSMIC) database and searched for peptides that can be presented by the common HLA class II alleles in Japanese, using in silico HLA-peptide binding prediction (NetMHCIIpan4.0). For the selected peptides, we measured their interaction with HLA class II. Among the candidate peptides, we identified seven ESR1 and ten PIK3CA mutated peptides that could be presented by HLA class II. These findings indicate a possibility that these peptides would be candidates for peptide-vaccine.

Free Research Field

乳癌

Academic Significance and Societal Importance of the Research Achievements

がん免疫療法の治療効果は、遺伝子変異が多く免疫原性の高いがんに対して効果的であることが知られているが、近年では免疫原性の低い固形がん領域でも、ネオアンチゲンワクチン併用により効果が高まることが報告され、今まで対象とされなかった癌腫においても効果の高い免疫療法の開発が期待されている。乳癌全体の約7割を占めるホルモン受容体陽性乳癌において免疫原性を示すネオアンチゲンの情報は十分に得られていないことから、本研究では我々はそのような変異を含む領域を見出すことを目的に研究を行った。