Detailed analysis of inflammatory cell infiltration in colorectal cancer

Abstract

Background:Higher-grade inflammatory infiltrate is a promising marker for better prognosis in colorectal cancer (CRC). However, the knowledge on the interrelationships between different inflammatory cells and classifications is fragmentary.Methods:We analysed the densities of eight types of inflammatory cells in a prospectively recruited group of 117 CRC patients and determined their interrelationships and contributions to Klintrup–Mäkinen (K–M) score of overall peritumoural inflammation. We characterised the inflammatory infiltrate in relation to stage and recurrences in 24-month follow-up.Results:There were high positive correlations between the inflammatory cell densities, with the exception of mast cells and CD1a+ immature dendritic cells. High K–M score associated with high peri- and intratumoural densities of CD3+, CD8+, CD68+, CD83+, and FoxP3+ cells and neutrophils. Advanced stage associated with low K–M score, as well as low CD3+, CD8+, CD83+, and FoxP3+ cell counts, of which low K–M score, low CD3+ T-cell count, and low FoxP3+ T-cell count were linked to higher recurrence rate.Conclusion:The density of CRC inflammatory infiltrate declines as stage advances. Especially, low K–M score and low T-cell counts predict higher recurrence rate. The high positive correlations between the individual inflammatory markers support the value of overall inflammatory reaction scoring.

Diagnostic value of inflammatory cell infiltrates, tumor stroma percentage and disease-free survival in patients with colorectal cancer

“…Moreover, the degree of inflammatory infiltration was negatively correlated with the the presence of lymph node metastasis, its size, exceeding the lymph pouches and infiltration structures near to metastatic lymph nodes. Our results are consistent with the observations of Galon et al (12), Menon et al (24) and Väyrynen et al (25). They confirmed that patients with high TNM stage linked with presence of distant metastases were correlated with lower immune response.…”

172: Serum endostatin levels are elevated in colorectal cancer and correlate with invasion and systemic inflammatory markers

“…Interestingly, we found a negative correlation between serum endostatin levels and the numbers of mast cells and immature DCs in tumour stroma and mature DCs at the invasive front. Our earlier study (Väyrynen et al, 2013) showed that CD1a þ immature DC and mast cell counts, unlike T cell and CD83 þ mature DC counts, do not associate with stage, and these two cell types clustered far apart from other inflammatory cells in the hierarchical clustering, suggesting that these cell types are less relevant in tumourassociated immune responses. Instead, it has been reported that immature DCs and especially mast cells promote angiogenesis in certain conditions (Huang et al, 1994;Maltby et al, 2009;Fainaru et al, 2010).…”

“…Immunohistochemical analyses of collagen XVIII (rabbit polyclonal antibody QH48) and inflammatory cell markers were carried out on formalin-fixed paraffin-embedded 3.5-mm sections as described earlier (Saarela et al, 1998;Väyrynen et al, 2013). The inflammatory cell markers used in this study were CD3 (T cells), CD8 (cytotoxic T cells), FoxP3 (regulatory T cells), CD68 (monocyte-macrophage lineage cells), neutrophil elastase (neutrophilic granulocytes), mast cell tryptase (mast cells), CD83 (mature dendritic cells (DCs)) and CD1a (immature DCs) (Väyrynen et al, 2013). Bound antibodies were detected using peroxidase-based EnVision kit (Dako, Copenhagen, Denmark).…”

“…3,3'-Diaminobenzidine was used as the chromogen and all sections were counterstained with haematoxylin. Cells were quantitated by using image analysis and the quantity of blood vessels surrounded by collagen XVIII-expressing basement membrane was evaluated on a 4-tiered scale from the captured images of the invasive front and the tumour stroma (Väyrynen et al, , 2013.…”

Prognostic Value of the Tumour-Infiltrating Dendritic Cells in Colorectal Cancer: A Systematic Review

“…The anomalous phenotype of the tumour can encourage an infl ow of infl ammatory lymphocytes into tissues around the tumour. This ability of the immune system to function as a prime defence against cancer, to respond, recognise and eradicate any emerging or established tumour areas, acts as an indication of the aggressiveness of the tumour and also as a predictor for disease outcomes (Klintrup et al, 2005;V ä yrynen et al, 2013). Different types of immune cells infi ltrate the tumour microenvironment, comprising cells of both the innate and adaptive immune system.…”