Differential cytokine and chemokine expression after ablation vs. resection in colorectal cancer liver metastasis

Nicola Frenkel; Susanna Poghosyan; Jan Willem van Wijnbergen; Inne Borel Rinkes; Onno Kranenburg; Jeroen Hagendoorn

doi:10.1016/j.sopen.2024.01.005

Differential cytokine and chemokine expression after ablation vs. resection in colorectal cancer liver metastasis

Surg Open Sci. 2024 Jan 14:18:29-34. doi: 10.1016/j.sopen.2024.01.005. eCollection 2024 Mar.

Authors

Nicola Frenkel¹, Susanna Poghosyan¹, Jan Willem van Wijnbergen¹, Inne Borel Rinkes¹, Onno Kranenburg¹, Jeroen Hagendoorn¹

Affiliation

¹ Laboratory for Translational Oncology, University Medical Center Utrecht and Utrecht University, Heidelberglaan 100, 3584CX Utrecht, the Netherlands.

Abstract

Background: Surgical resection remains the main curative treatment for colorectal liver metastases (CRLM). Radiofrequency ablation (RFA) is increasingly employed for small, deep lying or otherwise inoperable lesions. However, RFA can induce pro-tumorigenic effects on residual tumor cells, hereby possibly promoting tumor recurrence. Contrastingly, post-RFA tumor debris as an antigen source can also generate anti-cancer immune responses. Utilizing this, current studies on combining RFA with immune therapy appear promising. Here, in an attempt to shed light on this controversy, cytokines involved in inflammation, (lymph)angiogenesis, immune cell recruitment and tumor cell invasion were investigated post-RFA versus post-resection in CRLM patients.

Methods: Cytokine and chemokine serum levels pre-operation, 4 h and 24 h post-operation were analyzed in CRLM patients undergoing RFA (n = 8) or partial hepatectomy (n = 9) using Multiplex immunoassays. Statistical analyses were performed between as well as within individual intervention groups.

Results: Post-RFA, significantly increased levels of acute phase proteins SAA1 and S100A8, IL-6, IL-1Ra, MIP3b (CCL19) and MMP9 were observed along with decreases in Fibronectin, MCP-1 (CCL2), and Tie-2. Post-resection, increased levels of PDGFbb, I309 (CCL1), Apelin, MIF, IL-1b and TNFα were seen. All p-values <0.05.

Conclusion: Pro-inflammatory responses mediated by different cytokines were seen after both RFA and resection, possibly influencing residual tumor cells and tumor recurrence. As both ablation and resection trigger inflammation and immune cell recruitment (albeit via distinct mechanisms), these data suggest that further research may explore combining immune therapy with not only RFA but also resection.

Key message: Analysis of patients' serum after radiofrequency ablation versus resection of colorectal liver metastases (CRLM) showed that these interventions trigger inflammation and immune cell recruitment, via different cyto- and chemokine pathways. This suggests a possible future strategy of combining immune therapy with not only ablative techniques but also with resection of CRLM.

Keywords: Chemokine; Colorectal cancer; Cytokine; Hepatectomy; Liver metastasis; Radiofrequency ablation.