Improvement of cancer immunotherapy by combining molecular targeted therapy

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Constitutive activation of signaling pathways (MAPK, STAT3, β-catenin) in cancer cells drives immunosuppression.
• Tumor microenvironments exhibit immunosuppressive conditions due to cancer-derived molecules and cells.
• Cancer cytokines impair immune cells by activating signaling molecules like STAT3.

Purpose of the Study:

• To investigate how signaling pathways contribute to cancer-induced immunosuppression.
• To explore the potential of targeting these pathways for cancer therapy.

Main Methods:

• Analysis of signaling pathways (MAPK, STAT3, β-catenin) in human cancer cells.
• Identification of immunosuppressive molecules (TGF-β, IL-10, IL-6, VEGF, CCL2) and immune cells (Tregs, DCs, MDSCs).
• Evaluation of signal inhibitors' effects on cancer-immune networks.

Main Results:

• Activated signaling pathways trigger immunosuppressive cascades, producing immunosuppressive molecules and cells.
• Tumor microenvironments are enriched with immunosuppressive factors and cells.
• Signal inhibitors can disrupt these cascades by targeting key regulatory points.

Conclusions:

• Targeting shared signaling pathways simultaneously in cancer and immune cells is a viable therapeutic strategy.
• Combining signal inhibitors with immunotherapy holds promise for enhancing cancer treatment outcomes.