Abstract

BackgroundPreliminary experimental studies have suggested that the in situ destruction of tumor tissue by local laser ablation (LA) may also stimulate host immunity against cancer. We investigated local and systemic induction of immune responses after laser ablation in the setting of residual tumor.MethodsA murine colorectal cancer (CRC) liver metastasis model was used. Selected tumors of liver CRC bearing mice and livers of mice without tumor induction were treated with LA. Liver and tumor tissues from the ablation sites and from distant sites were collected at various time points following LA and changes in CD3+ T cells and Kupffer cells (F4/80 marker) infiltration and the expression of interferon gamma (IFNγ) were investigated by immunohistochemistry and ELISpot. Base line levels of CD3+ T cells and Kupffer cells were established in untreated mice.ResultsThe presence of tumor induced significant accumulation of CD3+ T cells and Kupffer cells at the tumor-host interface, within the tumor vascular lakes and increased their baseline concentration within the liver parenchyma. LA of the liver induced accumulation of CD3+ T-cells and Kupffer cells at the site of injury and systemic induction of immune responses as discerned by the presence of IFNγ secreting splenocytes. LA of liver tumors induced significant increase of CD3+ T-cells at site of injury, within normal liver parenchyma, and the tumor-host interface of both ablated and distant tumors. In contrast Kupffer cells only accumulated in ablated tumors and the liver parenchyma but not in distant tumors. IFNγ expression increased significantly in ablated tumors and showed an increasing trend in distant tumors.ConclusionLaser ablation in addition to local tumor destruction induces local and systemic Th1 type immune responses which may play a significant role in inhibiting tumor recurrence from residual micrometastases or circulating tumor cells.

Highlights

  • Preliminary experimental studies have suggested that the in situ destruction of tumor tissue by local laser ablation (LA) may stimulate host immunity against cancer

  • Tumor induces accumulation of CD3+ T cells and Kupffer cells in liver and tumor tissues The presence of liver metastases increased the concentration of both CD3+ T cells and Kupffer cells in the liver parenchyma as seen in Figure 1

  • Laser ablation of liver tissue induces local and systemic immune responses This study examined local and systemic immunological effects of LA treatment on livers from animals with no tumors

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Summary

Introduction

Preliminary experimental studies have suggested that the in situ destruction of tumor tissue by local laser ablation (LA) may stimulate host immunity against cancer. The spatial distribution of metastases, Local thermal ablation was developed to increase the therapeutic options for patients with liver metastases [5,6]. This involves the application of laser, radiofrequency or microwave energy to the tumor. When applied as a minimally invasive technique, thermal ablation has a number of potential advantages including significantly lower morbidity, minimal destruction of normal liver tissue and transient changes in liver function enzymes, leading to a lesser regenerative response and the ability for repeated application [10,11,12,13]

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