Towards Immunotherapy-Induced Normalization of the Tumor Microenvironment

Area of Science:

• Oncology
• Immunology
• Cancer Biology

Background:

• Immunotherapies harness immune cells to fight cancer but are only curative for a subset of patients.
• The tumor microenvironment (TME) often suppresses anti-tumor immunity due to pathological angiogenesis and desmoplasia, impairing blood flow and nutrient delivery.
• Tumor microenvironment (TME) normalization, involving vascular normalization and fibroblast reprogramming, is a strategy to improve immunotherapy efficacy.

Purpose of the Study:

• To review current concepts and progress in TME normalization.
• To examine immunotherapy-induced TME normalization.
• To discuss combining vascular normalizing agents with immunotherapies.

Main Methods:

• Literature review summarizing current concepts in TME normalization.
• Review of studies on immunotherapy-induced TME normalization.
• Discussion of clinical considerations for combination therapies.

Main Results:

• The TME, characterized by abnormal vasculature and fibrosis, poses a significant barrier to immunotherapy.
• TME normalization strategies aim to reverse these abnormalities, potentially enhancing anti-tumor immunity.
• The mechanisms by which immunotherapies induce TME normalization are not fully understood.

Conclusions:

• Further understanding and application of TME normalization could significantly improve immunotherapy outcomes for a broader range of cancer patients.
• Combining vascular normalizing agents with immunotherapies holds promise for synergistic effects.
• Complete TME normalization is a key goal to maximize immunotherapy's potential.