Abstract: PO1851
M2-Like Macrophages in Injured-Kidney Cortex Promoted Kidney Cancer Progression via the Inhibition of CD8 T Cell Infiltration
Session Information
- Cancer and Kidney Diseases: Nephrotoxins, RCC, and More
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Onco-Nephrology
- 1500 Onco-Nephrology
Authors
- Ishii, Taisuke, Tokyo Daigaku, Bunkyo-ku, Tokyo, Japan
- Tanaka, Tetsuhiro, Tokyo Daigaku, Bunkyo-ku, Tokyo, Japan
- Nangaku, Masaomi, Tokyo Daigaku, Bunkyo-ku, Tokyo, Japan
Background
Chronic kidney disease (CKD) affects mortality of the cancer patients, especially kidney cancer. However, the biological mechanism remains unknown. Recently, several studies showed that M2-like macrophages had pro-tumor in the tumor effects as well as pro-fibrotic roll in the injured kidney. We aimed to assess the effect of M2-like macrophages in the injured kidney on kidney cancer progression.
Methods
We injected murine kidney cancer cells on renal subcapsule 14 days after unilateral ischemic reperfusion injury (IRI) or aristolochic acid (AA) administration which were used as an injured kidney model. We evaluated cancer progression 20 days after tumor injection and examined macrophage characteristics and intra-tumor T cell population by flow cytometry. To assess the effect of M2-like macrophages on cancer progression and intra-tumor T cell, we used the adoptive transfer of M2-like macrophages collected from the tumor on IRI-treated kidneys and liposomal clodronate (CL) which removed M2-like macrophages from IRI-treated kidneys. We examined whether the inhibition of T cell infiltration contributed to tumor progression in CL-treated IRI kidneys and sham-treated IRI kidneys by using anti-CD8 or anti-CD4 antibodies.
Results
Kidney cancer on IRI kidneys (IRI-KC) was more progressive than that on sham-operated kidneys (Sham-KC). M2-like macrophages accumulated in the IRI-kidney cortex and IRI-KC. Interestingly, the intra-tumor T cell population decreased in IRI-KC compared to Sham-KC. The same phenomenon was observed in the AA model. T cell function and regulatory T cell infiltration were not different between IRI-KC and Sham-KC. Besides, the adoptive transfer experiment showed that kidney cancer co-injected with M2-like macrophages was more progressive than that with Other-type macrophages and intra-tumor T cell decreased in the M2-like macrophage co-injection group. Contrarily, the CL experiment showed that M2-like macrophage depletion from the IRI-kidney cortex inhibited tumor progression and increased tumor infiltrated CD8 T cell. And CD8 T cell removal after M2-like macrophage depletion abrogated this tumor-inhibiting effect, however, CD4 T cell removal didn’t affect tumor progression.
Conclusion
M2-like macrophages in injured kidneys promoted kidney cancer progression through the inhibition of CD8 T cell infiltration.