The intratumoural subsite and relation of CD8+ and FOXP3+ T lymphocytes in colorectal cancer provide important prognostic clues

Abstract

Background:To find improved tools for prognostic evaluation in patients with colorectal cancer (CRC), we have analysed how infiltration of cytotoxic T lymphocytes (CD8+) and regulatory T lymphocytes (FoxP3+) correlates to prognosis, not only according to quantity and relation, but also to subsite within tumours of different molecular characteristics (microsatellite instability and CpG island methylator phenotype status).Methods:CD8 and FOXP3 expression was evaluated by immunohistochemistry in 426 archival tumour tissue samples from patients surgically resected for CRC. The average infiltration of CD8+ and FOXP3+ cells was assessed along the tumour invasive front, in the tumour centre and within the tumour epithelium (intraepithelial).Results:We found that infiltration of CD8+ T lymphocytes within the tumour epithelium provided the strongest prognostic information (P<0.001). At the tumour invasive front and tumour centre, FOXP3 expression withheld the strongest association to prognosis (P<0.001), suggesting FOXP3+ T-lymphocyte infiltration to be a better prognostic tool than CD8+ T lymphocytes at these intratumoural subsites. We further analysed the possible prognostic impact of the relation between these T-cell subsets, finding that a high intraepithelial CD8 expression was associated with a better patient outcome, independent of FOXP3 infiltration. In groups of low intraepithelial CD8 expression, however, a high infiltration rate of FOXP3+ cells at the tumour invasive front, significantly improved prognosis.Conclusions:Analyses of intraepithelial infiltration of CD8+ T lymphocytes, infiltration of FOXP3+ T lymphocytes at the tumour front or centre, and the relation between these subsets, may be a valuable tool for predicting prognosis in colon cancer.

Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers

“…2). The majority support a positive impact on prognosis associated with extensive memory T-cell infiltration in the same cancers we discussed earlier, eg, CRC (Anitei et al, 2014;Boissi ere-Michot et al, 2014;Correale et al, 2012;Kim, Bae, et al, 2015;Ling et al, 2014;Ong et al, 2015;Shinto et al, 2014), bladder (Ingels et al, 2014), breast de Kruijf et al, 2013;García-Martínez et al, 2014;Kim et al, 2013;Mohammed et al, 2013;Park et al, 2012;Rathore et al, 2014;Seo et al, 2013;West et al, 2013), Merkel cell carcinoma (Paulson et al, 2014), glioma (Han et al, 2014), pancreatic (Ino et al, 2013;Tang et al, 2014), head and neck (Balermpas et al, 2014;Czystowska et al, 2013;Millrud et al, 2012;Wallis et al, 2015), cervical (Origoni et al, 2013), NSCLC Hald et al, 2013), gastric Feichtenbeiner et al, 2014;Kim et al, 2014), ovarian (Bachmayr-Heyda et al, 2013;Nielsen et al, 2012;Preston et al, 2013), and HCC (Cariani et al, 2012;Chen et al, 2012;Guo et al, 2007;Huang et al, 2012) (Table 1 and Fig. 2).…”

Arsenic trioxide inhibits lung metastasis of mouse colon cancer via reducing the infiltration of regulatory T cells

“…In addition, a high concentration of local tumor-infiltrating Tregs is the most crucial factor affecting the prognosis of patients with colon cancer [25–27]. Thus, reducing the number of local tumor-infiltrating Tregs may be of more clinical significance.…”

Association of FoxP3 rs3761548 polymorphism with susceptibility to colorectal cancer in the Chinese population

“…Ling's group reported that a high infiltration rate of FOXP3(?) cells at the tumor invasion front pointed to improved prognosis [21]. Thus, FOXP3(?…”