Current Challenges in Targeting Tumor Desmoplasia to Improve the Efficacy of Immunotherapy

Area of Science:

• Oncology
• Immunology
• Cancer Metabolism

Background:

• Desmoplasia plays a critical role in the development, progression, and immune evasion of malignancies.
• Targeting desmoplasia-related metabolic pathways presents a novel therapeutic strategy against anti-tumor resistance.

Purpose of the Study:

• To review promising metabolic pathways associated with desmoplasia.
• To discuss emerging strategies for reprogramming desmoplasia to enhance immunotherapy efficacy.

Main Methods:

• Literature review of preclinical and clinical studies.
• Analysis of therapeutic targets including CXCL12/CXCR4 axis, CD40L, FAPα, and DDR2.
• Exploration of metabolic pathway reprogramming in desmoplasia.

Main Results:

• CXCL12/CXCR4 inhibition reduces fibrosis, immunosuppression, and improves PD-1 immunotherapy efficacy.
• CD40L therapy may enhance T-cell activity and prolong survival.
• FAPα antagonists and DDR2 targeting show potential in preclinical models for reducing immune resistance, angiogenesis, and overcoming therapy adaptation.

Conclusions:

• Reprogramming desmoplasia offers a promising approach to enhance current cancer treatments and overcome therapeutic resistance.
• Targeting desmoplasia can potentially cooperate with existing and future therapeutic strategies to improve patient outcomes.