Elucidation and overcoming of the mechanism of chemoresistance by tumor-associated macrophages in esophageal cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17686
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kobe University
• Principal Investigator: Urakawa Naoki 神戸大学, 医学研究科, 助教 (20647763)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 食道癌 / マクロファージ / 化学療法

Outline of Final Research Achievements

Preoperative chemotherapy for cStage II/III esophageal cancer remains associated with poor prognosis, and the mechanisms of resistance to chemotherapy, particularly tumor-associated macrophages (TAMs) and tumor CD8-positive infiltrating lymphocytes (TILs) in the cancer microenvironment, need to be clarified. In the present study, we observed a trend toward an increased percentage of CD163- and CD204-positive TAM infiltration in cancer tissues, a trend toward an enhanced ability of TAMs to suppress antitumor effects under 5-FU and cisplatin in vivo, and changes in INF-γ and TIL cell numbers in the experimental co-culture system TAMs in the co-culture system suggested an inhibitory effect of TAMs on TIL proliferation.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

食道癌に対する化学療法の進展は目覚ましく、近年免疫療法などの導入も積極的に行われている。化学療法や免疫療法による腫瘍微小環境の変化を解明することは、食道癌治療成績の向上へ繋がることが期待される。今回の研究においては、化学療法下における特に腫瘍関連マクロファージの腫瘍進展への関与を解析しており、今後の治療の発展の一助になる可能性が示唆された。