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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Procedure: Hepatic RFA
* Procedure: Primary tumor resection


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 32 Years
Maximum Age: 78 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| RFA group<br>patients who received hepatic RFA followed by primary tumor resection were assigned to the RFA group | Procedure: Hepatic RFA<br>* Hepatic RFA was performed under guidace of ultrasonography (US) or computed tomography (CT) before primary tumor resection.<br>Procedure: Primary tumor resection<br>* Primary tumor resection were performed pre- or post-RFA for liver metastases.<br>|
| Non-RFA group<br>patients who received initial primary tumor resection without RFA | Procedure: Primary tumor resection<br>* Primary tumor resection were performed pre- or post-RFA for liver metastases.<br>|

What is the study measuring?
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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 |