Identification of STING agonist transporter in cancer cells by utilizing a lineage barcoding system

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21553
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: KITAJIMA Shunsuke 公益財団法人がん研究会, がん研究所 細胞生物部, 研究員 (90566465)
• Co-Investigator(Kenkyū-buntansha): 日野原 邦彦 名古屋大学, 医学系研究科, 特任准教授 (50549467)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: cGAMP / STING / STINGアゴニスト

Outline of Final Research Achievements

Although STING activation in cancer cells drives antitumor immunity, stimulation of cancer cell-intrinsic STING signaling by STING agonist is limited due to low cell-membrane permeability. In this study, we attempted to identify a novel transporter/regulator of STING agonist by utilizing a lineage barcoding system which can compare the gene expression profile at the single cell level between before and after treatment of STING agonist. We can classify the cells into a cell group showing high sensitivity and low sensitivity, and extract the gene candidates related with the sensitivity to STING agonist. In the future, we will analyze the candidate genes whether they can directly regulate the sensitivity to STING agonist in cancer cells by using in vitro model.

Free Research Field

腫瘍細胞生物学

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害薬はがん治療に革命をもたらしたが、一部のがん患者にしか奏功しない。しかし、抗ウイルス応答を活性化させるSTINGアゴニストをがん細胞内に効率的に導入することで、免疫細胞のがんに対する免疫応答を誘導することができる。STINGアゴニストががん細胞内に取り込まれる分子機構は未解明な点が多く、それらを解き明かし制御することで、免疫チェックポイント阻害薬に対する治療抵抗性の克服を目指す。