The Prognostic Significance of FoxP3+ T Cells and CD8+ T Cells in Colorectal Carcinomas

Argon, Asuman; Vardar, Enver; Kebat, Tülu; Erdinç, Ömer; Erkan, Nazif

doi:10.1615/jenvironpatholtoxicoloncol.2016014602

Cited by 11 publications

(6 citation statements)

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“…A flowchart of study selection is presented in Figure 1 . A total of 18 articles were included in our current meta-analysis (Frey et al, 2010 ; Lee et al, 2010 ; Suzuki et al, 2010 ; Sellitto et al, 2011 ; Salama et al, 2012 ; Kim et al, 2013 ; Xu et al, 2013 ; Chen and Chen, 2014 ; Ganapathi et al, 2014 ; Liu et al, 2014 ; Reimers et al, 2014 ; Zeestraten et al, 2014 ; Vlad et al, 2015 ; Argon et al, 2016 ; Chen et al, 2016 ; Markl et al, 2016 ; Saito et al, 2016 ; Zhu et al, 2016 ), including 5 on CSS (Frey et al, 2010 ; Sellitto et al, 2011 ; Salama et al, 2012 ; Vlad et al, 2015 ; Markl et al, 2016 ), 9 on OS (Lee et al, 2010 ; Suzuki et al, 2010 ; Kim et al, 2013 ; Xu et al, 2013 ; Chen and Chen, 2014 ; Ganapathi et al, 2014 ; Reimers et al, 2014 ; Argon et al, 2016 ; Chen et al, 2016 ), 6 on DFS (Lee et al, 2010 ; Suzuki et al, 2010 ; Reimers et al, 2014 ; Argon et al, 2016 ; Chen et al, 2016 ; Saito et al, 2016 ) and 8 on clinicopathological features (Frey et al, 2010 ; Lee et al, 2010 ; Kim et al, 2013 ; Liu et al, 2014 ; Reimers et al, 2014 ; Zeestraten et al, 2014 ; Markl et al, 2016 ; Zhu et al, 2016 ).…”

Section: Resultsmentioning

confidence: 87%

“…Accumulating evidence demonstrated that, in the majority of solid tumors, a high density of tumor-infiltrating FoxP3 + Tregs predicted an impaired patient survival (Wolf et al, 2005 ; Hiraoka et al, 2006 ; Miller et al, 2006 ; Takenaka et al, 2013 ; O'callaghan et al, 2015 ). Paradoxically, not only no significant correlation between increased frequency of FoxP3 + Tregs and prognosis involving CRC patients was found in recent researches (Suzuki et al, 2010 ; Salama et al, 2012 ; Xu et al, 2013 ), but also several studies even reported that high FoxP3 + Tregs infiltration might be linked with a favorable prognosis in CRC (Reimers et al, 2014 ; Vlad et al, 2015 ; Argon et al, 2016 ; Chen et al, 2016 ).…”

Section: Introductionmentioning

confidence: 97%

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The Clinicopathological and Prognostic Implications of FoxP3+ Regulatory T Cells in Patients with Colorectal Cancer: A Meta-Analysis

Fan

Zhang

et al. 2017

Front. Physiol.

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Background and Objective: Forkhead box P3 (FoxP3) is known as the specific marker for regulatory T lymphocytes (Tregs), which are responsible for self-tolerance and disturb the antitumor immunity. However, the prognostic implication of tumor-infiltrating FoxP3+ Tregs in patients with colorectal cancer (CRC) still remains controversial. The aim of this present study was to investigate the prognostic role of FoxP3+ Tregs in CRC through meta-analysis.Methods: PubMed, Embase and Web of Science were searched for relevant articles up to December 12, 2016. Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated to explore the prognostic value of FoxP3+ Tregs in CRC. Odds ratio (OR) was calculated to investigate the correlation between FoxP3+ Tregs and pathological parameters.Results: A total of 18 studies comprising 3,627 patients with CRC were enrolled in our meta-analysis. The combined HR for FoxP3+ Tregs on cancer-specific survival was 0.70 (95% CI = 0.62–0.80, P < 0.001). High FoxP3+ Tregs level was also associated with favorable prognosis on overall survival (HR = 0.76, 95% CI = 0.58–1.01, P = 0.058), with P-value very close to the statistical threshold. Yet, there was no correlation between FoxP3+ Tregs infiltration and disease-free survival (HR = 0.83, 95% CI = 0.63–1.09, P = 0.182). Moreover, FoxP3+ Tregs infiltration was significantly correlated with pT stage (OR = 0.50, 95% CI = 0.39–0.65, P < 0.001), tumor grade (OR = 0.77, 95% CI = 0.61–0.98, P = 0.032), lymphatic invasion (OR = 0.25, 95% CI = 0.07–0.89, P = 0.033) and vascular invasion (OR = 0.67, 95% CI = 0.52–0.86, P = 0.001).Conclusion: The present meta-analysis suggests that high FoxP3+ Tregs infiltration is inclined to indicate favorable prognosis and is associated with the pathogenesis of CRC. Immunotherapy targeting Tregs in patients with CRC should be further investigated.

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Section: Resultsmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 97%

The Clinicopathological and Prognostic Implications of FoxP3+ Regulatory T Cells in Patients with Colorectal Cancer: A Meta-Analysis

Fan

Zhang

et al. 2017

Front. Physiol.

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“…According to a previous report, the prognostic role of FOXP3+Treg in colorectal cancer is controversial. Nevertheless, in many reports, FOXP3+ TILs were positively related to the survival [21, 59]. In the analysis of different anatomical locations, it appears that FOXP3+ TILs was an independent and positive prognostic factor only in the rectum [28].…”

Section: Discussionmentioning

confidence: 99%

The prognostic value of tumor-infiltrating lymphocytes in colorectal cancer differs by anatomical subsite: a systematic review and meta-analysis

Zhao

et al. 2019

World J Surg Onc

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Purpose In colorectal cancer (CRC), whether the immune score can be used to predict the clinical prognosis of the patient has not been completely established. Besides, the prognostic values of tumor-infiltrating lymphocytes (TILs) in different anatomical locations, counting sites, and subtypes have been controversial. The purpose of this meta-analysis is to analyze and determine the prognostic value of TILs indices including TIL subsets, infiltrating sites, and anatomical sites. Methods Relevant literature was obtained by searching PubMed and Google Scholar. The pooled hazard ratio (HR) of the overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) was computed to investigate the prognostic significance of CD3+, CD8+, CD45RO+, and FOXP3+ T cells. Results A total of 22 studies involving 5108 patients were included in the meta-analysis. In CC, based on T cell subtypes analysis, the final results indicated that CD8+ and FOXP3+ infiltrating cells, but not CD3+ T cells were prognostic markers for DFS and OS. In addition, with regard to the counting location of TILs, subgroup analysis revealed that only high FOXP3+ infiltrates in the tumor stroma (ST) were significantly associated with OS (HR = 0.38, 95% confidence interval (CI) = 0.22–0.67, P = 0.0007), whereas in invasive margin (IM), high density of CD3+ infiltrating cells indicated increased DFS (HR = 0.76, 95% CI = 0.62–0.93, P = 0.008). At the tumor center (TC), high CD8+ T cells infiltration was associated with improved DFS (HR = 0.50, 95% CI = 0.38–0.65, P < 0.00001). In RC, whether CSS or OS, high-density TIL was associated with improved prognosis. Conclusion In a single counting site, high-density TILs reflect favorable prognostic value in CC or RC. For CC, more prospective studies are needed to verify whether different anatomical sites affect the distribution of TILs and thus the prognosis of patients. For RC, further studies should analyze the prognostic value of the immune score. Electronic supplementary material The online version of this article (10.1186/s12957-019-1621-9) contains supplementary material, which is available to authorized users.

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“…In contrast to other types of cancers, initial studies on patients affected by CRC failed to identify any correlation between Treg and disease prognosis [84][85][86]. More recently, a positive correlation with earlier CRC stage and overall survival have been shown [87][88][89].…”

Section: Tregs In Sporadic Crcmentioning

confidence: 99%

Tumor Infiltrating Regulatory T Cells in Sporadic and Colitis-Associated Colorectal Cancer: The Red Little Riding Hood and the Wolf

Fantini

Favale

Onali

et al. 2020

IJMS

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Regulatory T cells represent a class of specialized T lymphocytes that suppress unwanted immune responses and size the activation of the immune system whereby limiting collateral damages in tissues involved by inflammation. In cancer, the accumulation of Tregs is generally associated with poor prognosis. Many lines of evidence indicate that Tregs accumulation in the tumor microenvironment (TME) suppresses the immune response against tumor-associated antigens (TAA), thus promoting tumor progression in non-small cell lung carcinoma (NSLC), breast carcinoma and melanoma. In colorectal cancer (CRC) the effect of Tregs accumulation is debated. Some reports describe the association of high number of Tregs in CRC stroma with a better prognosis while others failed to find any association. These discordant results stem from the heterogeneity of the immune environment generated in CRC in which anticancer immune response may coexists with tumor promoting inflammation. Moreover, different subsets of Tregs have been identified that may exert different effects on cancer progression depending on tumor stage and their location within the tumor mass. Finally, Tregs phenotypic plasticity may be induced by cytokines released in the TME by dysplastic and other tumor-infiltrating cells thus affecting their functional role in the tumor. Here, we reviewed the recent literature about the role of Tregs in CRC and in colitis-associated colorectal cancer (CAC), where inflammation is the main driver of tumor initiation and progression. We tried to explain when and how Tregs can be considered to be the “good” or the “bad” in the colon carcinogenesis process on the basis of the available data concluding that the final effect of Tregs on sporadic CRC and CAC depends on their localization within the tumor, the subtype of Tregs involved and their phenotypic plasticity.

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The Prognostic Significance of FoxP3+ T Cells and CD8+ T Cells in Colorectal Carcinomas

Cited by 11 publications

References 0 publications

The Clinicopathological and Prognostic Implications of FoxP3+ Regulatory T Cells in Patients with Colorectal Cancer: A Meta-Analysis

The Clinicopathological and Prognostic Implications of FoxP3+ Regulatory T Cells in Patients with Colorectal Cancer: A Meta-Analysis

The prognostic value of tumor-infiltrating lymphocytes in colorectal cancer differs by anatomical subsite: a systematic review and meta-analysis

Tumor Infiltrating Regulatory T Cells in Sporadic and Colitis-Associated Colorectal Cancer: The Red Little Riding Hood and the Wolf

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