Role of Foxp3-positive Tumor-infiltrating Lymphocytes in the Histologic Features and Clinical Outcomes of Hepatocellular Carcinoma

Mathai, Alka Mary; Kapadia, Monesh; Alexander, Jacob; Kernochan, Lauren E.; Swanson, Paul E.; Yeh, Matthew M.

doi:10.1097/pas.0b013e31824e9b7c

Cited by 60 publications

(45 citation statements)

References 33 publications

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“…An intra-epithelial location of CTLs could possibly mean a more effective protection in that aspect. Tregs have been known to counteract the anti-tumour immune response in some cancers (Deschoolmeester et al , 2011; Mathai et al , 2012), but its role cannot be assessed as unambiguous as we still cannot see the whole picture. In this study, a high infiltration of FOXP3 + cells seems to be a protective factor, associated with a very good patient outcome, whereas the reverse can be said for patients with a very low infiltration, results that are consistent with the works of Salama et al (2009), Ladoire et al (2011b) and Frey et al (2010).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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“…Increased levels of CD4+ CD25+ Tregs have been reported in peripheral blood and the tumor microenvironment of patients with non–small cell lung carcinoma [89], gastrointestinal malignancies [90], ovarian cancer [91], SCC of the head and neck [92], hepatocellular carcinoma [93], breast cancer, pancreatic cancer [94] and prostate carcinoma [95]. Tregs variably present within the tumor microenvironment [96].…”

Section: Immune Cells With Pro-tumor Functionsmentioning

confidence: 99%

Clinical evaluation of systemic and local immune responses in cancer: time for integration

Gutkin

Shurin

2013

Cancer Immunol Immunother

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The immune system has a dual role in cancer development and progression. On the one hand, it can eradicate emerging malignant cells, but on the other hand, it can actively promote growth of malignant cells, their invasive capacities and their ability to metastasize. Immune cells with predominantly anti-tumor functionality include cells of the innate immune system, such as natural killer cells, and cells of adaptive immunity, such as conventional dendritic cells and cytotoxic T lymphocytes. Immune cells with predominantly pro-tumor functionality include a broad spectrum of cells of the innate and adaptive immune system, such as type 2 neutrophils and macrophages, plasmacytoid DC, myeloid-derived suppressor cells and regulatory T lymphocytes. The presence of immune cells with tumor-suppressive and tumor-promoting activity in the cancer microenvironment and in peripheral blood is usually associated with good clinical outcomes and poor clinical outcomes, respectively. Significant advances in experimental and clinical oncoimmunology achieved in the last decade open an opportunity for the use of modern morphologic, flow cytometric and functional tests in clinical practice. In this review, we describe an integrated approach to clinical evaluation of the immune status of cancer patients for diagnostic purposes, prognostic/predictive purposes (evaluation of patient prognosis and response to treatment) and for therapeutic purposes.

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“…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).…”

Section: Study Characteristicsmentioning

confidence: 99%

Prognostic significance of regulatory T lymphocytes in patients with hepatocellular carcinoma

Zhang

Qian

Zheng

2016

J. Zhejiang Univ. Sci. B

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Abstract:We investigated the prognostic role of regulatory T cells (Tregs) in patients with hepatocellular carcinoma (HCC). Relevant evidence regarding prognostic significance of Tregs was systematically searched in MEDLINE and Embase databases. A meta-analysis was performed to compare survival in patients with high or low Tregs level (either in peripheral blood or tumor). Eighteen studies were identified that fulfilled for the eligibility criteria and were included for data synthesis. Our pooled hazard ratios (HRs) demonstrated that increased Tregs intratumoral accumulation was significantly associated with worse overall survival (HR=2.04, 95% confidence interval (CI): 1.72-2.42) and diseasefree survival (HR=1.82, 95% CI: 1.58-2.09). Three studies evaluated the role of Tregs in peripheral blood, and all of them showed that increased peripheral Tregs correlated with shortened disease-free and overall survival. Collectively, our results showed that the increased Tregs count is tightly associated with the shortened survivals. Its measurement in either primary tumor or even circulation might be a candidate marker of prognostic significance in HCC patients.

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Role of Foxp3-positive Tumor-infiltrating Lymphocytes in the Histologic Features and Clinical Outcomes of Hepatocellular Carcinoma

Cited by 60 publications

References 33 publications

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

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

Clinical evaluation of systemic and local immune responses in cancer: time for integration

Prognostic significance of regulatory T lymphocytes in patients with hepatocellular carcinoma

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