Identification of tumor antigens that activate immune responses in heterogeneous breast cancers

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08968
• 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: Fujita Health University (2022); Keio University (2020-2021)
• Principal Investigator: Arima Yoshimi 藤田医科大学, がん医療研究センター, 客員准教授 (20309751)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: がんの不均一性

Outline of Final Research Achievements

Intratumor heterogeneity is a critical factor in cancer progression and therapeutic resistance. To clarify the molecular mechanisms of immunotherapies aimed at eradicating breast cancer, we established various mouse models that reflect the tumor microenvironment (TME), including the immune system. Based on our lung adenocarcinoma mouse models, we found that the TME induced solid-to-acinar transition (SAT) in lung cancer cells and that SAT contributes to tumor heterogeneity. The tumor tissues that formed in our cholangiocarcinoma mouse models were heterogeneous tissue rich in stroma containing fibroblasts and immune cells in addition to cancer cells, and is very similar to the histopathological features of human cholangiocarcinoma. We also reported that the interactions between cancer cells and cancer-associated fibroblasts are involved in tumor immunosuppression in heterogeneous tumor tissues.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

がんはゲノム的にも形質的にも多様であり、異なる性質を持つ不均一ながん細胞の集団と、その微小環境で構成される複雑な組織である。がんの不均一性は、がんのさらなる悪性化を誘導し、治療を困難にする要因と考えられており、また、不均一な腫瘍組織内でのがん細胞と線維芽細胞の相互作用が腫瘍免疫抑制に関与すると考えられている。本研究によって構築したマウスモデルに形成された腫瘍組織は、ヒトの腫瘍組織の病理像と酷似しており、免疫系を含め腫瘍の微小環境を反映したよりヒトに近いマウスモデルである。このマウスモデルを基盤として、乳がんの根治につながる免疫治療法のための分子基盤および分子機構が解明できると考えられる。