Hepatic RFA Increases T Cell Infiltraion and PD-L1 Expression in Primary Colorecatl Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Study type: Observational

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.
    

Intervention name(s): Hepatic RFA; Primary tumor resection
Intervention type(s): Procedure; Procedure
Intervention description(s): Hepatic RFA was performed under guidace of ultrasonography (US) or computed tomography (CT) before primary tumor resection.; Primary tumor resection were performed pre- or post-RFA for liver metastases.
Observational model: Case-Control
Time perspective: Retrospective
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.
      
Biospecimen description: 
      Paraffin-embedded tissues of endoscopic biopsy specimen and matched resected primary tumor
      specimen