Abstract 3212: IL2-mediated modulation of sEV secretion and PD-L1 expression: A novel perspective for neutralizing immune suppression within cancer cells

Abstract IL2 is known to induce anticancer effects by activating immune cells expressing the IL2 receptor complex (IL2R). However, the potential impact of IL2 on cancer cells expressing IL2R, such as melanoma cells, has been understudied. Here, we demonstrate that IL2 significantly reduces the secretion of small extracellular vesicles (sEVs) and expression of programmed death ligand 1 (PD-L1) in melanoma cells, while increasing their sensitivity to CD8+ T cell-mediated cytotoxicity. These effects are mediated through the activation of IL2R-MEK/ERK signaling in melanoma cells. To evaluate the direct effects of IL2 on melanoma cells in vivo, we developed a mouse model in which melanoma cells were engineered to express IL2 on their surface for self-stimulation. In this model, IL2 stimulation inhibited tumor growth and reduced PD-L1 expression in tumor tissues and plasma. Similar patterns were observed in lung cancer clinical samples. Our findings suggest that IL2 can directly elicit an anticancer immune response in IL2R-bearing cancers, highlighting its potential application in immunotherapy as an immune checkpoint modulator. Citation Format: Soojeong Noh, Suyeon Ryu, Dokyung Jung, Sanghee Shin, Inseong Jung, Sung-Min Kang, Christine Seulki Kim, Sung-Jin Choi, Hanchae Cho, Melanie Schwämmle, Youngtae Jeong, Felicitas Bucher, Il-Kyu Choi, Shin Yup Lee, Sin-Hyeog Im, Kyungmoo Yea, Moon-Chang Baek. IL2-mediated modulation of sEV secretion and PD-L1 expression: A novel perspective for neutralizing immune suppression within cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3212.