NCT02475889

Hepatic RFA Increases T Cell Infiltraion and PD-L1 Expression in Primary Colorecatl Cancer

Hepatic Radiofrequency Ablation Increases T Cell Infiltraion and PD-L1 Expression in Primary Tumor in Patients With Synchronous Colorectal Cancer Liver Metastases

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 78 (actual)
• Sponsor: The First People's Hospital of Changzhou · Academic / Other
• Sex: All
• Age: 32 Years – 78 Years
• Healthy volunteers: Not accepted

Summary

It has been shown that RFA induced systemic tumor antigen-specific T cell responses in human carcinoma. However, there are insufficient studies on the immune modulation of tumor microenviroment (TME) outside of the ablation zone. In order to study how RFA modifies TME in human cancer patients, investigators performed a retrospective study of a unique cohort of patients who suffered from synchronous CRCLM.

Detailed description

Radiofrequency ablation (RFA) is widely used as a local treatment for tumors such as small hepatocellular carcinomas, renal cancer and solitary colorectal cancer liver metastases (CRCLM). RFA induces localized coagulation necrosis and leads to the release of large amounts of cellular debris in situ, which can serve as a source of tumor antigens to elicit host adaptive immune responses against tumors. Several studies on preclinical animal models have shown that localized tumor ablation by RFA can induce systemic T-cell mediated antitumor immunity. Antigen-specific T cell immune responses were also observed in patients with hepatic tumors after RFA therapy. However, the RFA-induced immune responses are not sufficient to prevent tumor recurrence. The underlying mechanisms remain obscure. Programmed death-ligand 1 (PD-L1), an important immune checkpoint molecule, is often up-regulated on tumor cells and tumor associated myeloid cells. It impairs T cell-mediated immune responses upon engagement with its cognate co-inhibitory receptor PD-1, which is always highly expressed on tumor-infiltrating lymphocytes. PD-L1 expression can be induced by pro-inflammatory cytokines, especially type I interferon (IFN), as an important self-limiting mechanism to prevent rampant autoimmunity. Recent studies show that PD-L1 expression on tumor cells is associated with T cell infiltration, suggesting PD-L1 is actively involved in suppressing antitumor immune responses in the tumor microenvironment (TME). Whether the PD-L1/PD1 axis is involved in modulating the antitumor T cell immune responses induced by RFA is unclear. The objective of this investigation was to study the RFA-induced immune responses in tumor tissues from cancer patients.

Conditions

• Colorectal Cancer

Interventions

Type	Name	Description
PROCEDURE	Hepatic RFA	Hepatic RFA was performed under guidace of ultrasonography (US) or computed tomography (CT) before primary tumor resection.
PROCEDURE	Primary tumor resection	Primary tumor resection were performed pre- or post-RFA for liver metastases.

Timeline

• Start date: 2007-11-01
• Primary completion: 2015-01-01
• Completion: 2015-01-01
• First posted: 2015-06-19
• Last updated: 2015-06-19