Abstract
Background
Colorectal cancer (CRC) treatment commonly involves surgery combined with chemotherapy (CT) and/or radiotherapy (RT), which can trigger acute and chronic immune alterations. Understanding treatment-related inflammation is critical, as persistent immune dysregulation may influence therapeutic response, toxicity, and long-term outcomes. This study investigates longitudinal changes in inflammatory markers among CRC patients from pre-treatment to two years post-diagnosis and compares them to a matched cancer-free control group to isolate treatment-related effects.
Materials and Methods
Data were drawn from the PROCORE study (n = 411), and a sex- and age-matched normative sample (n = 204). Inflammatory markers (IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-17A, IL-22, CRP, IFN-γ, sTNFRI, sTNFRII) were measured at diagnosis (pre-treatment), and 12- and 24-month follow-ups. Linear mixed models assessed longitudinal biomarker trajectories across treatment groups (CT, RT, both, neither), controlling for demographic and clinical covariates. Group differences in inflammatory markers were compared to normative reference values.
Results
Across timepoints, CRC patients exhibited persistently altered biomarker levels compared with controls (higher IFN-γ, IL-1β, IL-10; lower IL-6, IL-8, sTNFRI), partly independent of treatment modality. Significant time x treatment interactions were visible for IL-6, IL-8, IL-17A, IL-22, sTNFRI and sTNFRII, with most post-hoc differences between RT only and CT only groups.
Conclusion
Chronic immune alterations in CRC patients appear only partly attributable to treatment type, suggesting broader cancer-related immune dysregulation. These findings highlight the importance of incorporating immune monitoring into clinical care and raise the potential for therapeutic strategies targeting inflammation to mitigate late effects.
Colorectal cancer (CRC) treatment commonly involves surgery combined with chemotherapy (CT) and/or radiotherapy (RT), which can trigger acute and chronic immune alterations. Understanding treatment-related inflammation is critical, as persistent immune dysregulation may influence therapeutic response, toxicity, and long-term outcomes. This study investigates longitudinal changes in inflammatory markers among CRC patients from pre-treatment to two years post-diagnosis and compares them to a matched cancer-free control group to isolate treatment-related effects.
Materials and Methods
Data were drawn from the PROCORE study (n = 411), and a sex- and age-matched normative sample (n = 204). Inflammatory markers (IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-17A, IL-22, CRP, IFN-γ, sTNFRI, sTNFRII) were measured at diagnosis (pre-treatment), and 12- and 24-month follow-ups. Linear mixed models assessed longitudinal biomarker trajectories across treatment groups (CT, RT, both, neither), controlling for demographic and clinical covariates. Group differences in inflammatory markers were compared to normative reference values.
Results
Across timepoints, CRC patients exhibited persistently altered biomarker levels compared with controls (higher IFN-γ, IL-1β, IL-10; lower IL-6, IL-8, sTNFRI), partly independent of treatment modality. Significant time x treatment interactions were visible for IL-6, IL-8, IL-17A, IL-22, sTNFRI and sTNFRII, with most post-hoc differences between RT only and CT only groups.
Conclusion
Chronic immune alterations in CRC patients appear only partly attributable to treatment type, suggesting broader cancer-related immune dysregulation. These findings highlight the importance of incorporating immune monitoring into clinical care and raise the potential for therapeutic strategies targeting inflammation to mitigate late effects.
| Original language | English |
|---|---|
| Number of pages | 17 |
| Journal | Clinical Colorectal Cancer |
| Volume | 10 |
| Issue number | 53 |
| DOIs | |
| Publication status | Accepted/In press - 10 Dec 2025 |
Keywords
- colorectal cancer
- chemotherapy
- radiotherapy
- Inflammation
- biomarkers
- PROCORE