TGF-beta: a master immune regulator

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Transforming Growth Factor-Beta (TGF-β) is a key regulator of cellular functions, including immune responses.
• In cancer, TGF-β promotes tumor growth through immunosuppression, potentially overriding other immune checkpoints.
• Current immune checkpoint inhibitors benefit only a subset of patients, indicating a need for broader targeting strategies.

Purpose of the Study:

• To review therapeutic agents targeting TGF-β signaling pathways for cancer treatment.
• To propose TGF-β as a master immune checkpoint in cancer.
• To explore TGF-β's role in predicting response to immunotherapies.

Main Methods:

• Literature review of therapeutic agents targeting TGF-β and its signaling pathways.
• Analysis of TGF-β's role in the tumor microenvironment and its association with treatment resistance.
• Evaluation of current biomarkers for immunotherapy response.

Main Results:

• TGF-β overexpression is a common hallmark of multiple cancer types, associated with excluded or "cold" tumors.
• TGF-β presence correlates with resistance to existing immune checkpoint inhibitors.
• Existing biomarkers (PD-1, PD-L1, MSI, TMB) are insufficient for predicting immunotherapy response.

Conclusions:

• TGF-β may function as a master checkpoint, influencing the efficacy of other immune checkpoint inhibitors.
• Targeting TGF-β could represent a novel therapeutic strategy to overcome treatment resistance.
• TGF-β status holds potential as a predictive biomarker for immunotherapy responsiveness.