Prognostic potential of FOXP3 expression in non-small cell lung cancer cells combined with tumor-infiltrating regulatory T cells

Tao, Hiroyuki; Mimura, Yusuke; Aoe, Keisuke; Kobayashi, Seiki; Yamamoto, Hiromasa; Matsuda, Eriko; Okabe, Kazunori; Matsumoto, Tsuneo; Sugi, Kazurou; Ueoka, Hiroshi

doi:10.1016/j.lungcan.2011.06.002

Cited by 218 publications

(165 citation statements)

References 33 publications

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“…Tregs suppress or down-regulate induction and proliferation of effector T cells and have been found to be consistently observed at a high frequency in patients with HNSCC (19,20). Surprisingly, unlike other solid malignancies including lung cancer and renal cell cancer, the presence of Tregs has been found to correlate with good clinical outcome (21)(22)(23). Multiple functions of Tregs explain this paradox, including suppression of inflammation triggered by immune cells, elimination of macrophages that have a protumor effect in cancer development and induction of apoptosis (24).…”

Section: Immune System and Cancer Developmentmentioning

confidence: 99%

The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications

Economopoulou¹,

Perisanidis²,

Giotakis³

et al. 2016

Ann. Transl. Med.

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Head and neck squamous cell carcinoma (HNSCC) carries a poor prognosis, with low survival rates for advanced stage tumors and minimal improvement in survival trends through the past decades. It is becoming increasingly clear that HNSCC oncogenesis and evolution is characterized by profound immune defects, as cancer cells evade immunosurveillance due to accumulation of genetic mutations and tumor heterogeneity. Improved understanding of the role of the immune system in cancer has led to the identification of novel therapeutic targets, which are being investigated for their potential to provide durable responses. In this review, we will summarize the role of the immune system in HNSCC, the rationale behind immunotherapy strategies and their clinical applications.

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Section: Immune System and Cancer Developmentmentioning

confidence: 99%

The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications

Economopoulou¹,

Perisanidis²,

Giotakis³

et al. 2016

Ann. Transl. Med.

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“…In the end, we reviewed 58 studies encompassing 16 different cancer types (Table 1), including bladder (19), breast (21)(22)(23)(24)(25)(26)(27)(28), cervical (29,30), colorectal (12,(31)(32)(33)(34)(35)(36)(37)(38)(39), endometrial (40)(41)(42), gastric (14,(43)(44)(45)(46), head and neck (47), hepatocellular (48)(49)(50)(51)(52), lung (53,54), melanoma (55)(56)(57)(58), mesothelial (59), oral (4,(60)(61)(62)(63), ovarian (2,3,…”

Section: Introductionmentioning

confidence: 99%

The Prognostic Value of FoxP3+ Tumor-Infiltrating Lymphocytes in Cancer: A Critical Review of the Literature

deLeeuw

Kost

Kakal

et al. 2012

Clinical Cancer Research

386

307

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CD8þ tumor-infiltrating lymphocytes (TIL) are associated with survival in a variety of cancers. A second subpopulation of TIL, defined by forkhead box protein P3 (FoxP3) expression, has been reported to inhibit tumor immunity, resulting in decreased patient survival. On the basis of this premise, several groups are attempting to deplete FoxP3þ T cells to enhance tumor immunity. However, recent studies have challenged this paradigm by showing that FoxP3þ T cells exhibit heterogeneous phenotypes and, in some cohorts, are associated with favorable prognosis. These discrepant results could arise from differences in study methodologies or the biologic properties of specific cancer types. Here, we conduct the first systematic review of the prognostic significance of FoxP3þ T cells across nonlymphoid cancers (58 studies from 16 cancers). We assessed antibody specificity, cell-scoring strategy, multivariate modeling, use of single compared with multiple markers, and tumor site. Two factors proved important. First, when FoxP3 was combined with one additional marker, double-positive T cells were generally associated with poor prognosis. Second, tumor site had a major influence. FoxP3þ T cells were associated with poor prognosis in hepatocellular cancer and generally good prognosis in colorectal cancer, whereas other cancer types were inconsistent or understudied. We conclude that FoxP3þ T cells have heterogeneous properties that can be discerned by the use of additional markers. Furthermore, the net biologic effects of FoxP3þ T cells seem to depend on the tumor site, perhaps reflecting microenvironmental differences. Thus, depletion of FoxP3þ T cells might enhance tumor immunity in some patient groups but be detrimental in others.

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“…In breast cancer, FOXP3 was found to be down regulated compared to normal tissue [36].FOXP3expression in melanoma or pancreatic tumor cells may have Treg like activity thus suppressing effector T cell activity [21].From these observations,it seems likely that FOXP3 expression does not influence carcinogenesis and cancer development in uniform manner but it has a rather cancer type-depended function [34]. In NSCLC, [37] found no significant relationship between Treg count and tumor FOXP3status.In their study,patients without tumor FOXP3 expression and high Treg count had significant worse overall and relapse-free survival than other groups. Study suggested that the different expression of FOXP3 in tumor cells and infiltrating lymphocytes is affected by factors present in the tumor microenvironment such as PGE2, COX-2 and TGF-β [9].…”

Section: Results and Discussion:-mentioning

confidence: 99%

Immunohistochemical Estimation of Foxp3 Expression in T-Reg and Cancer Cells in Iraqi Lung Cancer Tissue.

Mugdadi¹,

Hussen²,

Ali³

2017

IJAR

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Prognostic potential of FOXP3 expression in non-small cell lung cancer cells combined with tumor-infiltrating regulatory T cells

Cited by 218 publications

References 33 publications

The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications

The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications

The Prognostic Value of FoxP3+ Tumor-Infiltrating Lymphocytes in Cancer: A Critical Review of the Literature

Immunohistochemical Estimation of Foxp3 Expression in T-Reg and Cancer Cells in Iraqi Lung Cancer Tissue.

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