ESTRO 2024 - Abstract Book

S5178

Radiobiology - Immuno-radiobiology

ESTRO 2024

[1] Jain et al., NOX4 links metabolic regulation in pancreatic cancer to endoplasmic reticulum redox vulnerability and dependence on PRDX4. Science Advances 2021 May 7;7(19):eabf7114. doi: 10.1126/sciadv.abf7114.

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Digital Poster

Radiotherapy combined icaritin promote cytotoxic T cell infiltration in tumor microenvironment.

Minmin Cao 1 , Zihao Wang 2 , Jie Yao 3 , Binghua Xiang 2 , Dongmei Hu 2 , Wenjun Liao 4 , Shichuan Zhang 4 , Jinyi Lang 4 , Yiling Wang 4 , Yue Zhao 4 1 Chengdu University of Traditional Chinese Medicine, School of Basic Medical Sciences, Chengdu, China. 2 University of Electronic Science and Technology of China, School of Medicine, Chengdu, China. 3 Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Basic research center, Chengdu, China. 4 Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, China

Purpose/Objective:

Radiotherapy played pivotal roles in curing cancer itself as well as shaping tumor immune microenvironment. Recent studies have been focused on combined strategies to magnify tumor control with local radiotherapy. Icaritin is a prenylflavonoid derivative from plants of the Epimedium genus, recently been implicated as a novel immune-modulator in cancer treatment. Here we investigated the anti-tumor potential of icaritin combined radiotherapy and its immune mechanisms.

Material/Methods:

Mice were inoculated with MC38 (murine colon adenocarcinoma) or LLC (murine lung adenocarcinoma) cell line and treated with radiotherapy (6 Gy × 3) and icaritin (intraperitoneal, 200mg, qd) to evaluate anti-tumor responses in vivo. Tumor volume and mice survival were compared in each group (control, RT, icaritin and RT + icaritin). Tumor infiltrating immune cells were analyzed by flowcytometry and RNA-seq. Cell viability were used to evaluated tumor growth inhibition in vitro with CCK8 among groups (control, RT, icaritin and RT + icaritin).

Results:

RT combined with icaritin significantly dampened tumor growth and prolonged animal survival in MC38 and LLC model (p ＜ 0.001). Mechanistically, RT combined with icaritin decreased both MC38 and LLC cell viability in vitro, and orchestrated tumor immune microenvironmental changes in vivo. The number of CD8 + T cells, especially cytotoxic IFNγ + CD8 + were significantly increased both in peripheral blood and tumor. Besides, the expression level of PD-L1 were upregulated in dendritic cells (CD11b + CD11c + MHCII + ) (data not shown).