Elevated stromal Foxp3+ regulatory T cells combined with low density CD8+ cytotoxic T cells are associated with colorectal metastatic tumour progression
Session type: Poster / e-Poster / Silent Theatre session
Several studies in colorectal cancer (CRC) patients indicate a relationship between tumour immune infiltrates and clinical outcome (Galon et al., 2006). The aim of our study was to analyse levels of Foxp3+ regulatory T cells (Tregs) and CD8+ cytotoxic T cells in areas of tumour, tumour associated stroma and adjacent non-neoplastic tissue, within primary and metastatic CRC samples. The study aims to correlate these findings with markers of proliferation (Ki67), apoptosis (cleaved caspase-3), hypoxia (HIF-1α) and vasculature (CD31).
Primary CRC with matched hepatic metastatic (n=7), primary CRC alone (n=18) and primary CRC with matched normal (n=40) FFPE tissue were analysed immunohistochemically. Automated quantitative image analysis of tumour, stroma and non-neoplastic regions using GenieTM pattern recognition software (Aperio Technologies Ltd.) was carried out, combined with appropriate analytical algorithms for each marker.
A significant increase in the prevalence of Tregs (p<0.0001, p<0.05) and CD8 (p<0.0001, p<0.05) cells was observed in the stroma of primary and metastatic CRC, respectively, compared to infiltration of tumour. A direct comparison between non-metastatic primary CRC (MET-) and primary CRC that resulted in metastasis (MET+) was conducted. Elevated Tregs (p<0.05) and reduced numbers of CD8 (p>0.05) were observed in MET+ compared to MET- samples. Within MET+ tissue, Tregs were elevated in adjacent non-neoplastic tissue, compared to distant non-neoplastic samples (p<0.0001).
Our study adds to the ongoing discussion on the role of immune cells in metastatic development. Increased numbers of immune infiltrates are observed within stroma compared to tumour. A metastatic phenotype has been alluded to, where elevation of Tregs and low density cytotoxic T cells, within primary tumour, is associated with metastasis. Accumulating evidence points to a critical role of immune infiltrates in allowing metastatic development, where Tregs may support tumour growth by suppressing the host anti-tumour immune response.