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- Title
Effect of M2-like macrophages of the injured-kidney cortex on kidney cancer progression.
- Authors
Ishii, Taisuke; Mimura, Imari; Nagaoka, Koji; Naito, Akihiro; Sugasawa, Takehito; Kuroda, Ryohei; Yamada, Daisuke; Kanki, Yasuharu; Kume, Haruki; Ushiku, Tetsuo; Kakimi, Kazuhiro; Tanaka, Tetsuhiro; Nangaku, Masaomi
- Abstract
Chronic 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.
- Subjects
KIDNEY cortex; RENAL cancer; MACROPHAGES; CANCER invasiveness; CANCER-related mortality; RENAL fibrosis; MONOCLONAL antibodies; T cells
- Publication
Cell Death Discovery, 2022, Vol 8, Issue 1, p1
- ISSN
2058-7716
- Publication type
Article
- DOI
10.1038/s41420-022-01255-3