Tumor-Infiltrating FOXP3<sup>+</sup> T Regulatory Cells Show Strong Prognostic Significance in Colorectal Cancer

Salama, Paul; Phillips, Michael; Grieu, Fabienne; Morris, M. J.; Zeps, Nikolajs; Joseph, David; Platell, Cameron; Iacopetta, Barry

doi:10.1200/jco.2008.18.7229

Cited by 907 publications

(789 citation statements)

References 37 publications

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“…Another explanation to the favourable impact of PD-L1 expression, contradicting results from other types of solid cancer, is that the immune cell infiltration in CRC might be associated with paradoxical features due to the microbiota of the colon. For example, in contrast with the majority of human cancers, the infiltration of FoxP3 + immune cells in CRC has in the herein investigated cohort 14 and others, 30 , 31 been found to be an auspicious prognostic factor. It should however be pointed out that the herein described inter-correlations between different subsets of immune cells merely reflect their co-localization in selected tumour regions.…”

Section: Discussionmentioning

confidence: 59%

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis

et al. 2018

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Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 has been demonstrated to confer a prognostic value in colorectal cancer (CRC), but no studies have investigated whether this association differs according to tumour location. In this study, immunohistochemical expression of PD-1 and PD-L1 was analysed in tissue microarrays with primary tumours from 557 incident CRC cases from a prospective population-based cohort. Univariable and multivariable Cox regression analyses, adjusted for age, sex, TNM stage, differentiation grade and vascular invasion, were applied to determine the impact of biomarker expression on 5-year overall survival (OS), in the entire cohort and in subgroup analysis of right colon, left colon, and rectum. High PD-L1 expression on tumour-infiltrating immune cells was an independent factor of a prolonged OS in the entire cohort (hazard ratio [HR] = 0.49; 95% confidence interval [CI] CI 0.35 – 0.68), and in tumours of the right colon (HR = 0.43; 95% CI 0.25 – 0.74) and the left colon (HR = 0.28; 95% CI 0.13 – 0.61), but not in rectal cancer. Tumour-specific PD-L1-expression was not prognostic, neither in the full cohort nor according to tumour location. High immune cell-specific PD-1 expression was associated with a prolonged OS in the entire cohort and in tumours of the right colon, but not in the left colon or rectum, and only in univariable analysis. In conclusion, these results demonstrate that immune cell-specific PD-L1 and PD-1 expression is prognostic in a site-dependent manner, whereas tumour-specific PD-L1-expression is not prognostic in CRC.

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Section: Discussionmentioning

confidence: 59%

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis

et al. 2018

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“…Such a good prognostic value of Tregs in head and neck cancer has subsequently been confirmed by others [98,99] and extended to additional solid neoplasms including colorectal carcinoma [100,101] and bladder cancer [102]. In some tumor types including hepatocellular carcinoma and breast cancer, high levels of intratumoral Tregs have been clearly associated with bad prognosis, whereas in other types such as colorectal cancer, head and neck carcinoma and lymphoma, robust tumor infiltration by Tregs frequently correlates with improved disease outcome [103,104].…”

Section: Clinical Significance Of Intratumoral Tregsmentioning

confidence: 78%

Tumor-Infiltrating Regulatory T Cells: Phenotype, Role, Mechanism of Expansion In Situ and Clinical Significance

Tanchot

Terme

Péré

et al. 2012

Cancer Microenvironment

119

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In immunocompetent individuals, the immune system initially eradicates potentially tumorigenic cells as they develop, a capacity that is progressively lost when malignant cells acquire alterations that sustain immunosubversion and/or immunoevasion. One of the major mechanisms whereby cancer cells block antitumor immune responses involves a specific class of immunosuppressive T cells that-in the vast majority of cases-express the Forkhead box P3 (FOXP3) transcription factor. Such FOXP3 + regulatory T cells (Tregs) accumulate within neoplastic lesions as a result of several distinct mechanisms, including increased infiltration, local expansion, survival advantage and in situ development from conventional CD4 + cells.

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“…In contrast, Ling et al [98] found no significant difference in Treg density between advanced and earlystage disease, but did not evaluate the association with patient survival. Salama et al [99] showed that a high density of FOXP3 + Tregs in CRC was associated with an improved survival and had a stronger prognostic significance than CD8 + and CD45RO + memory T lymphocytes in CRC. In contrast, a high density of FOXP3 + Tregs in normal colon of CRC patients was associated with worse prognosis.…”

Section: Foxp3 + Tregs Prognosis and Msi-statusmentioning

confidence: 99%

Immune Cells in Colorectal Cancer: Prognostic Relevance and Role of MSI

Deschoolmeester

Baay

Lardon

et al. 2011

Cancer Microenvironment

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There is growing evidence that both local and systemic inflammatory responses play an important role in the progression of a variety of solid tumors. Colorectal cancer (CRC) results from the cumulative effect of sequential genetic alterations, leading to the expression of tumor-associated antigens possibly inducing a cellular antitumor immune response. It is well recognized that cytotoxic lymphocytes (CTLs) constitute one of the most important effector mechanisms of anti-tumor-immunity. However, their potential prognostic influence in CRC remains controversial. In addition, other key players like natural killer cells, tumor associated macrophages and regulatory T cells play an important role in the immune attack against CRC and need further investigation. This review will mainly focus on the role of the adaptive immune system in CRC and particularly in regard to microsatellite instability.

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Tumor-Infiltrating FOXP3⁺ T Regulatory Cells Show Strong Prognostic Significance in Colorectal Cancer

Cited by 907 publications

References 37 publications

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis

Tumor-Infiltrating Regulatory T Cells: Phenotype, Role, Mechanism of Expansion In Situ and Clinical Significance

Immune Cells in Colorectal Cancer: Prognostic Relevance and Role of MSI

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Tumor-Infiltrating FOXP3+ T Regulatory Cells Show Strong Prognostic Significance in Colorectal Cancer

Cited by 907 publications

References 37 publications

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis

Tumor-Infiltrating Regulatory T Cells: Phenotype, Role, Mechanism of Expansion In Situ and Clinical Significance

Immune Cells in Colorectal Cancer: Prognostic Relevance and Role of MSI

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Tumor-Infiltrating FOXP3⁺ T Regulatory Cells Show Strong Prognostic Significance in Colorectal Cancer