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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02475889
• Other study ID #: RFAOO2
• Status: Completed
• Phase: N/A
• First received: June 6, 2015
• Last updated: June 16, 2015
• Start date: November 2007
• Est. completion date: January 2015

Study information

• Verified date: June 2015
• Source: The First People's Hospital of Changzhou
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Health and Family Planning Commission of Changzhou
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 32 Years to 78 Years

Eligibility

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 Design

Observational Model: Case Control, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
The First People's Hospital of Changzhou

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of T cell infiltraion in primary tumor	Number of T cell infiltraion in primary tumor was evaluated by immunohistochemical staining	2 weeks	No
Primary	PD-L1 expression in primary tumor	PD-L1 expression in primary tumor was evaluated by immunohistochemical staining	2 weeks	No