Complement factor H: a novel innate immune checkpoint in cancer immunotherapy

Front Cell Dev Biol. 2024 Feb 8:12:1302490. doi: 10.3389/fcell.2024.1302490. eCollection 2024.

Abstract

The elimination of cancer cells critically depends on the immune system. However, cancers have evolved a variety of defense mechanisms to evade immune monitoring, leading to tumor progression. Complement factor H (CFH), predominately known for its function in inhibiting the alternative pathway of the complement system, has recently been identified as an important innate immunological checkpoint in cancer. CFH-mediated immunosuppression enhances tumor cells' ability to avoid immune recognition and produce an immunosuppressive tumor microenvironment. This review explores the molecular underpinnings, interactions with immune cells, clinical consequences, and therapeutic possibilities of CFH as an innate immune checkpoint in cancer control. The difficulties and opportunities of using CFH as a target in cancer immunotherapy are also explored.

Keywords: complement; complement factor H; immune checkpoint; immunosuppression; immunotherapy; tumor micro-environment.

Publication types

  • Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was supported by the Department of Defense through Lung Cancer Research Program Translational Research Partnership Award No. W81XWH-19-1-0342 to EP and Y-WH, and by an award from the Sunny Li Family Fund to Y-WH.