美国宾夕法尼亚大学Malay Haldar研究组近日取得一项新成果，他们揭示了肿瘤产生的维甲酸调节肿瘤内单核细胞分化来促进免疫抑制。该项研究成果于2020年3月12日在线发表在《细胞》杂志上。

Title: Tumor-Derived Retinoic Acid Regulates Intratumoral Monocyte Differentiation to Promote Immune Suppression

Author: Samir Devalaraja, Tsun Ki Jerrick To, Ian W. Folkert, Ramakrishnan Natesan, Md Zahidul Alam, Minghong Li, Yuma Tada, Konstantin Budagyan, Mai T. Dang, Li Zhai, Graham P. Lobel, Gabrielle E. Ciotti, T.S. Karin Eisinger-Mathason, Irfan A. Asangani, Kristy Weber, M. Celeste Simon, Malay Haldar

Issue&Volume: 2020-03-12

Abstract: The immunosuppressive tumor microenvironment (TME) is a major barrier to immunotherapy.Within solid tumors, why monocytes preferentially differentiate into immunosuppressivetumor-associated macrophages (TAMs) rather than immunostimulatory dendritic cells(DCs) remains unclear. Using multiple murine sarcoma models, we find that the TMEinduces tumor cells to produce retinoic acid (RA), which polarizes intratumoral monocytedifferentiation toward TAMs and away from DCs via suppression of DC-promoting transcriptionfactor Irf4. Genetic inhibition of RA production in tumor cells or pharmacologic inhibitionof RA signaling within TME increases stimulatory monocyte-derived cells, enhancesT cell-dependent anti-tumor immunity, and synergizes with immune checkpoint blockade.Furthermore, an RA-responsive gene signature in human monocytes correlates with animmunosuppressive TME in multiple human tumors. RA has been considered as an anti-canceragent, whereas our work demonstrates its tumorigenic capability via myeloid-mediatedimmune suppression and provides proof of concept for targeting this pathway for tumorimmunotherapy.

DOI: 10.1016/j.cell.2020.02.042

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30219-1