Role of group 2 innate lymphoid cells in the lung cancer microenvironment

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18210
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Mie University
• Principal Investigator: Ito Atsushi 三重大学, 医学系研究科, リサーチアソシエイト (80783133)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 2型自然リンパ球 / がん / 腫瘍微小環境 / 骨髄由来免疫抑制細胞

Outline of Final Research Achievements

When breast cancer metastasizes to the lung, group 2 innate lymphoid cells (ILC2s) are thought to promote tumor growth via the activation of myeloid-derived suppressor cells (MDSCs). In this study, we aimed to characterize the dynamic interactions of ILC2s and MDSCs during the course of cancer progression from the micrometastatic to the macrometastatic stages. We found that ILC2s were activated in both the micro- and macrometastatic regions, suggesting sustained activation throughout the metastatic cascades. In addition, our findings indicate that ILC2s may induce the immunosuppressive functions of MDSCs during the later stages of metastasis.Concomitantly, ILC2 may instigate extracellular matrix remodeling by polymorphonuclear (PMN)-MDSC activation during the early stages of metastasis.
These metastatic-stage-specific changes may contribute to metastatic tumor growth in the microenvironment of breast cancer lung metastasis.

Free Research Field

呼吸器外科学

Academic Significance and Societal Importance of the Research Achievements

癌治療においては免疫チェックポイント阻害薬の開発により治療成績の向上が目覚ましいが、現状ではまだその効果が得られる患者は10-30%と限定的である。本研究では乳癌肺転移モデルマウスを用いて、乳癌肺転移においては2型リンパ球と骨髄由来免疫抑制細胞の相互作用により腫瘍増殖を許容する微小環境を構築している可能性を見出した。今後、腫瘍微小環境におけるこれらの自然免疫細胞の働きの解明が進むことで、更なる免疫療法の開発や癌予防に繋げていくことが期待される。