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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Procedure: Hepatic RFA; Procedure: Primary tumor resection

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.

• Study Type: Observational
• Enrollment (Actual): 78

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 32 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

A total of 391 consecutive patients with synchronous colorectal cancer liver metastases were initially included in this study. Among of them, 38 patients who received initial hepatic RFA followed by primary tumor resection were identified as RFA group, and the other 40 patients who received initial primary tumor resection were identified as Non-RFA group.

Description

Inclusion Criteria:

Patients with histologically confirmed asynchronous liver metastases received initial hepatic RFA or initial primary tumor resection.

Exclusion Criteria:

1. Preoperative CT, RT and other antitumor treatment
2. Emergency surgery
3. Initial hepatectomy
4. No qualified endoscopic biopsy

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
RFA group; patients who received hepatic RFA followed by primary tumor resection were assigned to the RFA group	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.
Non-RFA group; patients who received initial primary tumor resection without RFA	Procedure: Primary tumor resection; Primary tumor resection were performed pre- or post-RFA for liver metastases.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of T cell infiltraion in primary tumor	Number of T cell infiltraion in primary tumor was evaluated by immunohistochemical staining	2 weeks
PD-L1 expression in primary tumor	PD-L1 expression in primary tumor was evaluated by immunohistochemical staining	2 weeks

Collaborators and Investigators

• Sponsor: The First People's Hospital of Changzhou
• Investigators: Study Chair: Changping Wu, M.D., The First People's Hospital of Changzhou

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: June 6, 2015
• First Submitted That Met QC Criteria: June 16, 2015
• First Posted (Estimate): June 19, 2015

Study Record Updates

• Last Update Posted (Estimate): June 19, 2015
• Last Update Submitted That Met QC Criteria: June 16, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: RFAOO2