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Published on: November 28, 2019
New hope for tumor immunotherapy: the macrophage-related "do not eat me" signaling pathway
Han Deng1, Guan Wang1, Shengyan Zhao1
1General Practice Ward/International Medical Center, General Practice Medical Center, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan, China.
Abstract:
The "do not eat me" signaling pathway is extremely active in tumor cells, providing a means for these cells to elude macrophage phagocytosis and escape immune surveillance. Representative markers of this pathway, such as CD47 and CD24, are highly expressed in numerous tumors. The interaction of SIRPα with CD47 reduces the accumulation of non-myosin ⅡA on the cell membrane. The combination of CD24 and Siglec10 ultimately leads to the recruitment of SHP-1 or SHP-2 to reduce signal transduction. Both of them weaken the ability of macrophages to engulf tumor cells. Blocking the mutual recognition between CD47-SIRPα or CD24-Siglec10 using large molecular proteins or small molecular drugs represents a promising avenue for tumor immunotherapy. Doing so can inhibit signal transduction and enhance macrophage clearance rates of cancer cells. In this paper, we summarize the characteristics of the drugs that affect the "do not eat me" signaling pathway via classical large molecular proteins and small molecule drugs, which target the CD47-SIRPα and CD24-Siglec10 signaling pathways, which target the CD47-SIRPα and CD24-Siglec10 signaling pathways. We expect it will offer insight into the development of new drugs centered on blocking the "do not eat me" signaling pathway.
Insights
Tumor cells use the "do not eat me" pathway, involving CD47-SIRPα and CD24-Siglec10, to evade immune cells. Blocking these signals with drugs enhances macrophage cancer cell clearance for immunotherapy.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Tumor cells evade immune surveillance via the
- do not eat me
- signaling pathway, actively expressed in many cancers.
- Key markers like CD47 and CD24 are highly expressed on tumor cells, inhibiting macrophage phagocytosis.
- The CD47-SIRPα interaction and CD24-Siglec10 pathway suppress macrophage engulfment of cancer cells.
Purpose of the Study:
- To review drugs targeting the
- do not eat me
- signaling pathway.
- To summarize characteristics of large molecular proteins and small molecule drugs.
- To provide insights for developing novel immunotherapies targeting CD47-SIRPα and CD24-Siglec10.
Main Methods:
- Review of existing literature on drugs targeting the CD47-SIRPα and CD24-Siglec10 pathways.
- Analysis of drug characteristics, including large molecular proteins and small molecule drugs.
- Summary of mechanisms by which these drugs inhibit immune evasion.
Main Results:
- The
- do not eat me
- pathway involves CD47-SIRPα and CD24-Siglec10 interactions.
- Blocking these interactions with drugs enhances macrophage-mediated cancer cell clearance.
- Both large molecule proteins and small molecule drugs show potential in blocking these pathways.
Conclusions:
- Targeting the
- do not eat me
- signaling pathway is a promising cancer immunotherapy strategy.
- Inhibiting CD47-SIRPα or CD24-Siglec10 interactions can restore macrophage phagocytosis.
- Further drug development focusing on this pathway could lead to effective cancer treatments.
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