Effect of M2-like macrophages of the injured-kidney cortex on kidney cancer progression
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 kidne...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-12-01
|
| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-022-01255-3 |
| _version_ | 1811179162737573888 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Taisuke Ishii |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T06:30:07Z |
| format | Article |
| id | doaj.art-fea4fd389da749cf83f77efa217dce65 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-11T06:30:07Z |
| publishDate | 2022-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-fea4fd389da749cf83f77efa217dce652022-12-22T04:40:08ZengNature Publishing GroupCell Death Discovery2058-77162022-12-018111810.1038/s41420-022-01255-3Effect of M2-like macrophages of the injured-kidney cortex on kidney cancer progressionTaisuke Ishii0Imari Mimura1Koji Nagaoka2Akihiro Naito3Takehito Sugasawa4Ryohei Kuroda5Daisuke Yamada6Yasuharu Kanki7Haruki Kume8Tetsuo Ushiku9Kazuhiro Kakimi10Tetsuhiro Tanaka11Masaomi Nangaku12Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of MedicineDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of MedicineDepartment of Immunotherapeutics, The University of Tokyo HospitalDivision of Urology, The University of Tokyo Graduate School of MedicineLaboratory of Clinical Examination/Sports Medicine, Division of Clinical Medicine, Faculty of Medicine, University of TsukubaDepartment of Pathology, The University of Tokyo Graduate School of MedicineDivision of Urology, The University of Tokyo Graduate School of MedicineLaboratory of Clinical Examination/Sports Medicine, Division of Clinical Medicine, Faculty of Medicine, University of TsukubaDivision of Urology, The University of Tokyo Graduate School of MedicineDepartment of Pathology, The University of Tokyo Graduate School of MedicineDepartment of Immunotherapeutics, The University of Tokyo HospitalDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of MedicineDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of MedicineAbstract 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.https://doi.org/10.1038/s41420-022-01255-3 |
| spellingShingle | 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 Effect of M2-like macrophages of the injured-kidney cortex on kidney cancer progression Cell Death Discovery |
| title | Effect of M2-like macrophages of the injured-kidney cortex on kidney cancer progression |
| title_full | Effect of M2-like macrophages of the injured-kidney cortex on kidney cancer progression |
| title_fullStr | Effect of M2-like macrophages of the injured-kidney cortex on kidney cancer progression |
| title_full_unstemmed | Effect of M2-like macrophages of the injured-kidney cortex on kidney cancer progression |
| title_short | Effect of M2-like macrophages of the injured-kidney cortex on kidney cancer progression |
| title_sort | effect of m2 like macrophages of the injured kidney cortex on kidney cancer progression |
| url | https://doi.org/10.1038/s41420-022-01255-3 |
| work_keys_str_mv | AT taisukeishii effectofm2likemacrophagesoftheinjuredkidneycortexonkidneycancerprogression AT imarimimura effectofm2likemacrophagesoftheinjuredkidneycortexonkidneycancerprogression AT kojinagaoka effectofm2likemacrophagesoftheinjuredkidneycortexonkidneycancerprogression AT akihironaito effectofm2likemacrophagesoftheinjuredkidneycortexonkidneycancerprogression AT takehitosugasawa effectofm2likemacrophagesoftheinjuredkidneycortexonkidneycancerprogression AT ryoheikuroda effectofm2likemacrophagesoftheinjuredkidneycortexonkidneycancerprogression AT daisukeyamada effectofm2likemacrophagesoftheinjuredkidneycortexonkidneycancerprogression AT yasuharukanki effectofm2likemacrophagesoftheinjuredkidneycortexonkidneycancerprogression AT harukikume effectofm2likemacrophagesoftheinjuredkidneycortexonkidneycancerprogression AT tetsuoushiku effectofm2likemacrophagesoftheinjuredkidneycortexonkidneycancerprogression AT kazuhirokakimi effectofm2likemacrophagesoftheinjuredkidneycortexonkidneycancerprogression AT tetsuhirotanaka effectofm2likemacrophagesoftheinjuredkidneycortexonkidneycancerprogression AT masaominangaku effectofm2likemacrophagesoftheinjuredkidneycortexonkidneycancerprogression |