The Proliferative Role of Immune Checkpoints in Tumors: Double Regulation

Area of Science:

• Oncology
• Immunology
• Cell Biology

Background:

• Cancer immunotherapy is a major treatment modality, necessitating improved efficacy and safety.
• Identifying novel therapeutic targets is crucial for advancing tumor treatment strategies.
• Immune checkpoints play recognized roles in immune regulation and are increasingly implicated in tumor progression.

Purpose of the Study:

• To review the proliferative role of 15 key immune checkpoints in various cancers.
• To identify shared regulatory mechanisms, including cell cycle and signaling pathways.
• To explore potential interactions between immune checkpoints in regulating tumor proliferation.

Main Methods:

• Literature review of studies on immune checkpoints and tumor proliferation.
• Analysis of immune checkpoints including PD1, PD-L1, FGL1, CD155, CD47, SIRPα, CD276, IDO1, SIGLEC-15, TIM3, Galectin-9, CD70, CD27, 4-1BBL, and HVEM.
• Examination of associated signaling pathways such as PI3K, AKT, mTOR, and NF-κB.

Main Results:

• Multiple immune checkpoints (e.g., PD1/PD-L1, FGL1, CD155, CD47/SIRPα, CD276, SIGLEC-15) regulate the cell cycle, notably via Cyclin D1.
• Common signaling pathways (PI3K, AKT, mTOR, NF-κB) are involved in immune checkpoint-mediated proliferation.
• Interactions between PD1/PD-L1, CD47/SIRPα, TIM3/Galectin-9, and CD70/CD27 checkpoints in regulating tumor proliferation have been identified.

Conclusions:

• Most immune checkpoints exhibit a dual role in regulating both immunity and proliferation.
• Targeting proliferation-regulating pathways associated with immune checkpoints offers therapeutic potential.
• IDO1, SIGLEC-15, 4-1BBL, and HVEM show promise as novel targets for cancer therapy due to their role in proliferation.