Tumour radiosensitivity is associated with immune activation in solid tumours.

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Tumor radiosensitivity is a critical factor in radiation therapy efficacy.
• Immune system activation within the tumor microenvironment can influence treatment outcomes.
• Gene expression signatures (GESs) offer a molecular approach to quantify biological processes like radiosensitivity and immune response.

Purpose of the Study:

• To investigate the association between tumor radiosensitivity and immune system activation.
• To analyze this association across a wide range of solid tumor types using two distinct GESs.
• To explore the prognostic significance of these GESs in predicting distant metastasis-free survival (DMFS).

Main Methods:

• Analysis of 10,240 genomically profiled solid primary tumors with available gene expression data.
• Utilized a radiosensitivity index (RSI) GES (10 genes) and a 12-chemokine (12-CK) GES (12 genes).
• Exploratory analysis in 282 early-stage breast cancer patients treated with surgery and radiation alone to assess DMFS.

Main Results:

• RSI-low tumors (higher radiosensitivity) showed significantly higher 12-CK GES values (indicating immune activation) compared to RSI-high tumors (p < 0.001).
• In early-stage breast cancer, a composite model including age, RSI, and 12-CK significantly predicted DMFS (p = 0.02).
• Both RSI and 12-CK demonstrated comparable contributions in predicting DMFS in the breast cancer cohort.

Conclusions:

• Tumor radiosensitivity is demonstrably associated with immune activation, as evidenced by the inverse relationship between the RSI and 12-CK GESs.
• These findings suggest a potential interplay between intrinsic tumor radiosensitivity and the host immune response.
• The study highlights the utility of GESs in understanding complex tumor biology and predicting clinical outcomes.