| Literature DB >> 33158953 |
Britney Reese1, Ashok Silwal1, Elizabeth Daugherity1, Michael Daugherity2, Mahshid Arabi1, Pierce Daly1, Yvonne Paterson3, Layton Woolford4,5, Alana Christie4,5, Roy Elias4,5, James Brugarolas4,5, Tao Wang5,6, Magdalena Karbowniczek1, Maciej M Markiewski7.
Abstract
Preclinical studies demonstrated that complement promotes tumor growth. Therefore, we sought to determine the best target for complement-based therapy among common human malignancies. High expression of 11 complement genes was linked to unfavorable prognosis in renal cell carcinoma. Complement protein expression or deposition was observed mainly in stroma, leukocytes, and tumor vasculature, corresponding to a role of complement in regulating the tumor microenvironment. Complement abundance in tumors correlated with a high nuclear grade. Complement genes clustered within an aggressive inflammatory subtype of renal cancer characterized by poor prognosis, markers of T cell dysfunction, and alternatively activated macrophages. Plasma levels of complement proteins correlated with response to immune checkpoint inhibitors. Corroborating human data, complement deficiencies and blockade reduced tumor growth by enhancing antitumor immunity and seemingly reducing angiogenesis in a mouse model of kidney cancer resistant to PD-1 blockade. Overall, this study implicates complement in the immune landscape of renal cell carcinoma, and notwithstanding cohort size and preclinical model limitations, the data suggest that tumors resistant to immune checkpoint inhibitors might be suitable targets for complement-based therapy.Entities:
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Year: 2020 PMID： 33158953 PMCID： PMC7703597 DOI： 10.4049/jimmunol.2000511
Source DB: PubMed Journal: J Immunol ISSN： 0022-1767 Impact factor: 5.422