Immune Predictors of Radiotherapy Outcomes in Cervical Cancer

Area of Science:

• Oncology
• Immunology
• Radiotherapy Research

Background:

• The tumor immune microenvironment significantly impacts radiotherapy (RT) sensitivity, but resistance mechanisms are not fully understood.
• Identifying immune predictors is crucial for optimizing RT outcomes and developing personalized treatment strategies.

Purpose of the Study:

• To investigate the dynamic changes in the immune microenvironment following radiotherapy.
• To identify immune cell subsets and molecular interactions that predict patient response to RT.
• To develop a predictive model for stratifying patients based on RT outcomes.

Main Methods:

• Integration of single-cell transcriptomics and machine learning algorithms.
• Comprehensive analysis of immune cell populations, activation states, and intercellular communication (CellChat).
• Validation in preclinical murine models and development of a predictive prognostic model (CCRTIM).

Main Results:

• Radiotherapy alters the tumor microenvironment, characterized by reduced epithelial cells, increased apoptosis, and inflammation.
• Accumulation of M1-like HSPA1B+ macrophages with enhanced antigen-presenting capacity was observed post-RT.
• Increased T and NK cell cytotoxicity alongside exacerbated exhaustion markers (PDCD1, TIGIT) were noted.
• Epithelial-myeloid crosstalk via the C3/C3AR1 axis was identified as critical; C3AR1 antagonism reduced RT efficacy.
• An 8-feature model (CCRTIM) accurately predicted prognosis (AUC=0.76) and enabled risk stratification.

Conclusions:

• Radiotherapy induces significant immune remodeling within the tumor microenvironment.
• The C3/C3AR1 axis and specific macrophage subsets are key players in RT response.
• The developed CCRTIM model provides actionable biomarkers for enhancing precision radiotherapy in cervical cancer.