Tumor-Infiltrating FoxP3+ Tregs and CD8+ T Cells Affect the Prognosis of Hepatocellular Carcinoma Patients

Abstract

Purpose: Tumor-infiltrating lymphocytes are considered to represent a host immune response against tumor. This study was carried out to analyze the effect of both FoxP3+ regulatory T cells (Tregs) and CD8+ T lymphocytes in prognostic value of hepatocellular carcinoma (HCC) patients. Methods: Expressions of FoxP3, CD4, CD8 and CD34 in patient-matched tumors and peritumoral tissues were assessed by immunohistochemistry for 54 HCC patients. The prognostic effect of groups with high and low numbers was evaluated by the Kaplan-Meier and Cox model analysis using median values as a cutoff. Results: Compared with the corresponding peritumoral tissue, the density of intratumoral Tregs was significantly higher, while the density of intratumoral CD8+ T cells was lower (p < 0.001 and p = 0.013, respectively). In addition, tumor-infiltrating Tregs were positively correlated with microvessel density in tumors (r = 0.334, p = 0.020). The high intratumoral Tregs density group showed a significantly lower survival rate (overall survival, p = 0.018; disease-free survival, p = 0.029). Multivariate Cox analysis revealed that intratumoral Tregs density was an independent prognostic factor for HCC. Conclusions: Tumor-infiltrating Tregs may promote HCC progression by fostering angiogenesis and decreasing CD8+ T cells. High tumor-infiltrating Tregs are thought to be an unfavorable prognostic indicator for HCC.

B7-H1 and B7-H4 expression in colorectal carcinoma: Correlation with tumor FOXP3+ regulatory T-cell infiltration

“…These results provided the evidence that B7-H1 and B7-H1 molecules can clinically be used as a predictor of poor prognosis in CRC. Tregs have been shown to inhibit tumor-specific T cells immunity and thereby may contribute to the progression of human tumors (Nomura and Sakaguchi, 2005;Yuan et al, 2010;Huang et al, 2012;Kashimura et al, 2012;Gai et al, 2013). In the present study, we also detected tumor-infiltrating Tregs in the CRC tumor tissues and adjacent tissues.…”

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).…”

Prognostic significance of regulatory T lymphocytes in patients with hepatocellular carcinoma

“…Our search strategy yielded 573 primary articles, of which 16 were eventually identified fulfilling the eligibility criteria (Fu et al, 2007;Gao et al, 2007;Kobayashi et al, 2007;Sasaki et al, 2008;Cai et al, 2009;Ju et al, 2009a;2009b;Zhou et al, 2009;2010;Chen et al, 2011;Shen et al, 2011;Huang et al, 2012;Mathai et al, 2012;Wang et al, 2012;Lin et al, 2013) (Fig. 1).…”