Effect of M2-like macrophages of the injured-kidney cortex on kidney cancer progression

• DOI: 10.1038/s41420-022-01255-3
• Publication Date: 2022-12-05T11:02:37Z
• Authors: Taisuke Ishii; Imari Mimura; Koji Nagaoka; Akihiro Naito; Takehito Sugasawa; Ryohei Kuroda; Daisuke Yamada; Yasuharu Kanki; Haruki Kume; Tetsuo Ushiku; Kazuhiro Kakimi; Tetsuhiro Tanaka; Masaomi Nangaku
• Keywords: 0301 basic medicine; 03 medical and health sciences; QH573-671; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Cytology; RC254-282; Article; 3. Good health

AbstractChronic kidney disease (CKD) affects kidney cancer patients’ mortality. However, the underlying mechanism remains unknown. M2-like macrophages have pro-tumor functions, also exist in injured kidney, and promote kidney fibrosis. Thus, it is suspected that M2-like macrophages in injured kidney induce the pro-tumor microenvironment leading to kidney cancer progression. We found that M2-like macrophages present in the injured kidney promoted kidney cancer progression and induced resistance to anti-PD1 antibody through its pro-tumor function and inhibition of CD8+ T cell infiltration. RNA-seq revealed Slc7a11 was upregulated in M2-like macrophages. Inhibition of Slc7a11 with sulfasalazine inhibited the pro-tumor function of M2-like macrophages and synergized with anti-PD1 antibody. Moreover, SLC7A11-positive macrophages were associated with poor prognosis among kidney cancer patients. Collectively, this study dissects the characteristic microenvironment in the injured kidney that contributed to kidney cancer progression and anti-PD1 antibody resistance. This insight offers promising combination therapy with anti-PD1 antibody and macrophage targeted therapy.