TY - JOUR
T1 - Effect of M2-like macrophages of the injured-kidney cortex on kidney cancer progression
AU - Ishii, Taisuke
AU - Mimura, Imari
AU - Nagaoka, Koji
AU - Naito, Akihiro
AU - Sugasawa, Takehito
AU - Kuroda, Ryohei
AU - Yamada, Daisuke
AU - Kanki, Yasuharu
AU - Kume, Haruki
AU - Ushiku, Tetsuo
AU - Kakimi, Kazuhiro
AU - Tanaka, Tetsuhiro
AU - Nangaku, Masaomi
N1 - Funding Information:
This work was supported by the Japan Science and Technology Agency SPRING, Grant Number JPMJSP2108 (to TI); the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (20K08604 to IM; 20K08626 to TT; 18H02824 to MN); Takeda Science Foundation (to IM); The Naito Foundation (to IM). We thank Ms. Kahoru Amitani and Mr. Kei Sakuma for their excellent technical support.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41420-022-01255-3
DO - 10.1038/s41420-022-01255-3
M3 - Article
AN - SCOPUS:85143328355
SN - 2058-7716
VL - 8
JO - Cell Death Discovery
JF - Cell Death Discovery
IS - 1
M1 - 480
ER -
