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

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.

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Key information

Conditions

Colorectal Cancer Colonic Diseases Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases

Age range

32 year–78 year

Sex eligibility

All sexes

Study type

Observational

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

Preoperative CT, RT and other antitumor treatment
Emergency surgery
Initial hepatectomy
No qualified endoscopic biopsy

Treatment and study plan

Hepatic RFA

Procedure

Hepatic RFA was performed under guidace of ultrasonography (US) or computed tomography (CT) before primary tumor resection.

Primary Tumor Resection

Procedure

Primary tumor resection were performed pre- or post-RFA for liver metastases.

Primary outcomes

Number of T cell infiltraion in primary tumor

Time frame: 2 weeks

Number of T cell infiltraion in primary tumor was evaluated by immunohistochemical staining
PD-L1 expression in primary tumor

Time frame: 2 weeks

PD-L1 expression in primary tumor was evaluated by immunohistochemical staining

Sponsors and collaborators

Lead sponsor

The First People's Hospital of Changzhou

Other

Registry information

Official study title

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

Important dates

Study start: 2007
Primary completion: 2015
Study completion: 2015
First posted: Jun 19, 2015
Registry last updated: Jun 19, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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