Strategies to Improve Cancer Immune Checkpoint Inhibitors Efficacy, Other Than Abscopal Effect: A Systematic Review

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, particularly for melanoma and non-small cell lung cancer.
• However, response rates to ICIs remain low in several malignancies, including gastrointestinal cancers, breast cancer, sarcomas, and some genitourinary cancers.
• Predictive biomarkers like PD-L1 expression and tumor mutational burden are used to identify potential responders.

Purpose of the Study:

• To systematically review the literature on combination therapies aimed at improving ICI efficacy.
• To identify therapeutic strategies that modify the tumor immune microenvironment to enhance ICI response.
• To determine which novel agents are closest to clinical validation for combination therapy with ICIs.

Main Methods:

• Systematic literature review of studies investigating combination therapies with ICIs.
• Analysis of therapeutic approaches including microbiota modifiers, co-inhibitory receptor antagonists, anti-angiogenic agents, small molecules, and oncolytic viruses.
• Evaluation of evidence supporting the enhancement of ICI efficacy through modulation of the tumor immune microenvironment.

Main Results:

• Several combination strategies are under investigation to overcome ICI resistance.
• Therapies targeting the tumor immune microenvironment, such as microbiota modifiers and oncolytic viruses, show potential.
• Radiotherapy and anti-angiogenic agents are also explored for their synergistic effects with ICIs.

Conclusions:

• Combination therapies are crucial for improving ICI efficacy in a broader range of cancers.
• Further clinical validation is needed for novel agents like microbiota modifiers and oncolytic viruses.
• Optimizing the tumor immune microenvironment is key to enhancing responses to immune checkpoint inhibitors.