Mechanistic rationales for combining immunotherapy with radiotherapy.

Area of Science:

• Oncology
• Immunology
• Radiation Oncology

Background:

• Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by enhancing antitumor responses.
• Tumor immune micro-environment (TIME) responsiveness, particularly the presence of functional tumor-infiltrating lymphocytes (TILs), is critical for ICI efficacy.
• Tumors can develop resistance to ICIs through various immune escape mechanisms, leading to unresponsive TIME phenotypes.

Purpose of the Study:

• To review the generation and impairment of antitumor immunity.
• To discuss the immunogenic properties of radiotherapy.
• To explore the combined effects of radiotherapy and immunotherapy on antitumor immunity.

Main Methods:

• Literature review focusing on immunotherapy, tumor immune micro-environment, radiotherapy, and their combination.
• Analysis of mechanisms of immune escape and resistance to ICIs.
• Evaluation of radiation's effects on antigenicity and adjuvanticity.

Main Results:

• Radiotherapy can induce antitumor immunity in both primary and distant metastatic sites.
• Radiation enhances antigenicity and adjuvanticity, stimulating immune responses.
• Combining radiotherapy with ICIs can augment antitumor immunity, potentially overcoming resistance.

Conclusions:

• Radiotherapy holds potential for restoring antitumor immunity in tumors with unresponsive TIME.
• Combination therapy with radiotherapy and ICIs may offer a strategy to improve treatment outcomes for ICI-resistant cancers.
• Understanding radiation's immunogenic properties is key to optimizing combination strategies.