Development of a novel immunotherapy for lung cancer targeting Interleukin(IL)-38

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15507
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kyushu University (2023); National Hospital Organization, Kyushu Cancer Center (2021-2022)
• Principal Investigator: KINOSHITA Fumihiko 九州大学, 大学病院, 助教 (20875794)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 原発性肺癌 / 肺腺癌 / 腫瘍微小環境 / Interleukin / Interleukin-38 / 腫瘍関連好中球 / 腫瘍関連マクロファージ

Outline of Final Research Achievements

In this study, we evaluated the expression of Interleukin (IL)-38 in tumor cells, tumor-associated neutrophils (TANs), and tumor-associated macrophages (TAMs) through immunohistochemical staining in 209 specimens of surgically resected lung adenocarcinoma. Additionally, we established a mouse model by subcutaneously injecting lung cancer cell lines overexpressing IL-38 and assessed TANs and TAMs within the tumors. High expression of IL-38 in lung adenocarcinoma was significantly correlated with increased infiltration of TANs and TAMs. Consistently, in the mouse model, IL-38 overexpression resulted in elevated infiltration of TANs and TAMs. Our findings elucidate that IL-38 induces the infiltration of TANs and TAMs, suggesting the potential of IL-38 as a therapeutic target for lung cancer.

Free Research Field

腫瘍微小環境

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害薬の登場によって、原発性肺癌を含む多くの悪性腫瘍の治療成績が向上するとともに腫瘍微小環境への注目が高まった。我々は本研究において、2001年に発見された新規サイトカインのInterleukin (IL)-38の腫瘍微小環境における意義を研究した。本研究では臨床検体を用いた実験と動物実験を行い、IL-38によって腫瘍関連好中球(TANs)、腫瘍随伴マクロファージ(TAMs)の浸潤が誘導されることが明らかとなった。IL-38の原発性肺癌の腫瘍微小環境における役割がさらに明らかとなって新規免疫療法の開発に繋がれば、肺癌の治療成績が向上することが期待される。