Low-grade intestinal inflammation two decades after pelvic radiotherapy

Area of Science:

• Oncology
• Gastroenterology
• Immunology

Background:

• Pelvic radiotherapy effectively treats cancer but can cause long-term bowel complications.
• The underlying cause of these chronic bowel symptoms following radiotherapy remains unclear.
• There is ongoing debate regarding the presence of chronic inflammation in the late stages after pelvic radiation.

Purpose of the Study:

• To investigate the potential presence of chronic inflammation in the intestinal mucosa of pelvic cancer survivors.
• To understand the pathophysiology of chronic bowel symptoms after pelvic radiotherapy.

Main Methods:

• Proteomic and transcriptomic profiling of mucosal biopsies from 24 cancer survivors (2-20 years post-radiotherapy) and 4 controls using mass spectrometry and mRNA sequencing.
• Analysis of immune cell populations via flow cytometry.
• Assessment of mucus layer integrity and bacterial infiltration using permeability assays and 16S rRNA detection.

Main Results:

• Differential expression of 942 proteins in mucosa exposed to high versus low radiation doses.
• Evidence of chronic low-grade inflammation with neutrophil activity, confirmed by transcriptomic data and flow cytometry.
• A compromised mucus barrier with bacterial infiltration was observed.

Conclusions:

• Results challenge the notion that radiation-induced intestinal inflammation resolves or becomes fibrotic without progressing to chronic inflammation.
• Findings suggest a chronic inflammatory component in the late phase of pelvic radiotherapy.
• This study provides a basis for developing new strategies to manage chronic bowel symptoms in cancer survivors.