Improving radioresponse through modification of the tumor immunological microenvironment

Area of Science:

• Oncology
• Immunology
• Radiotherapy

Background:

• Tumor microenvironment (TME) components, including endothelial and immune cells, significantly influence radiotherapy outcomes.
• Fractionated radiotherapy efficacy can be reduced by hypoxia-inducible factor-1 α and vascular endothelial growth factor.
• Antiangiogenic therapies may be less effective due to the recruitment of proangiogenic cells to the TME.

Purpose of the Study:

• To emphasize the significance of radiation timing within a vascular normalization window.
• To discuss the critical role of immune cells within the tumor microenvironment in determining radiotherapy success.
• To explore the potential of combining radiotherapy and immunotherapy by modulating the tumor immunological microenvironment.

Main Methods:

• Review of existing literature on the tumor microenvironment's role in radioresponse.
• Analysis of the impact of vascular normalization windows on radiotherapy efficacy.
• Evaluation of the balance between different immune cell populations (favorable vs. unfavorable) in the TME.

Main Results:

• The interplay between endothelial cells, immune cells, and radiotherapy is crucial for treatment outcomes.
• Hypoxia-inducible factor-1 α and vascular endothelial growth factor can attenuate the benefits of fractionated radiotherapy.
• The balance of immune cells, such as cytotoxic T cells, NK cells, dendritic cells, tumor-associated macrophages, and regulatory T cells, dictates tumor control probability.

Conclusions:

• Strategic radiation timing and modulation of the tumor microenvironment are essential for enhancing radiotherapy effectiveness.
• Combining radiotherapy with immunotherapy, by targeting the tumor immunological microenvironment, holds promise for improved cancer treatment.
• A nuanced understanding of the tumor microenvironment's cellular components is key to optimizing cancer therapy.