Autophagy protein Atg5 regulates CD36 expression and anti-tumor MHC class Ⅱ antigen presentation in dendritic cells

Abstract

Autophagy protein Atg5 regulates CD36 expression and anti-tumor MHC class II antigen presentation in dendritic cells Dong Sun Oh1,2, Heung Kyu Lee1,2,3,* 1 Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea 2 Biomedical Science and Engineering Interdisciplinary Program, KAIST, Daejeon 34141, Republic of Korea 3KAIST Institute for Health Science and Technology, KAIST, Daejeon 34141, Republic of Korea *Corresponding author:

Autophagy has been implicated cytoplasmic and viral antigen presentation on class II major histocompatibility complex (MHC) molecules. However, the role of autophagy in the presentation of phagocytized tumor-associated antigens in vivo remains unclear. Following the administration of apoptotic tumor cells and in vivo chemotherapy, mice with a dendritic cell–specific deletion of Atg5, a key autophagy gene, exhibit reduced CD4+ T-cell priming but not CD8+ cytotoxic T-cell priming. Interestingly, Atg5-deficient dendritic cells have an elevated expression of scavenger receptor CD36 and show excessive lipid accumulation. Atg5-deficient dendritic cells increased CD36-dependent phagocytosis of apoptotic tumor cells. CD36 blockade restores elevated phagocytosis, increases CD4+ T-cell priming in dendritic cells, and intratumoral CD36 blockade inhibits tumor growth. Our results demonstrate that Atg5 is required for proper antigen phagocytosis and presentation to MHC class II via modulation of CD36 in dendritic cells and may be a future therapeutic target for anti-tumor therapy.

Keyword : Autophagy, Dendritic cell, Tumor, Antigen presentation