Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis

Shang, Bin; Liu, Yao; Jiang, Shujuan; Liu, Yi

doi:10.1038/srep15179

Cited by 799 publications

(694 citation statements)

References 50 publications

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“…In the majority of cancers, Treg cells demonstrate a marked negative effect on patient prognosis. High FoxP3 + Treg infiltration is strongly associated with a shorter overall survival in patients with melanoma whereas in other indications the impact of Treg cells is less clear 46. In this study, we demonstrate in an in vitro killing assay, that Treg cells used at an equal proportion with cytotoxic T cells fail to affect IMCgp100‐mediated target cell apoptosis.…”

Section: Discussionmentioning

confidence: 68%

Polyfunctional response by ImmTAC (IMCgp100) redirected CD8⁺ and CD4⁺ T cells

et al. 2017

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SummaryThe success of immune system‐based cancer therapies depends on a broad immune response engaging a range of effector cells and mechanisms. Immune mobilizing monoclonal T cell receptors (TCRs) against cancer (ImmTAC™ molecules: fusion proteins consisting of a soluble, affinity enhanced TCR and an anti‐CD3 scFv antibody) were previously shown to redirect CD8+ and CD4+ T cells against tumours. Here we present evidence that IMCgp100 (ImmTAC recognizing a peptide derived from the melanoma‐specific protein, gp100, presented by HLA‐A*0201) efficiently redirects and activates effector and memory cells from both CD8+ and CD4+ repertoires. Using isolated subpopulations of T cells, we find that both terminally differentiated and effector memory CD8+ T cells redirected by IMCgp100 are potent killers of melanoma cells. Furthermore, CD4+ effector memory T cells elicit potent cytotoxic activity leading to melanoma cell killing upon redirection by IMCgp100. The majority of T cell subsets belonging to both the CD8+ and CD4+ repertoires secrete key pro‐inflammatory cytokines (tumour necrosis factor‐α, interferon‐γ, interleukin‐6) and chemokines (macrophage inflammatory protein‐1α‐β, interferon‐γ‐inducible protein‐10, monocyte chemoattractant protein‐1). At an individual cell level, IMCgp100‐redirected T cells display a polyfunctional phenotype, which is a hallmark of a potent anti‐cancer response. This study demonstrates that IMCgp100 induces broad immune responses that extend beyond the induction of CD8+ T cell‐mediated cytotoxicity. These findings are of particular importance because IMCgp100 is currently undergoing clinical trials as a single agent or in combination with check point inhibitors for patients with malignant melanoma.

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Section: Discussionmentioning

confidence: 68%

Polyfunctional response by ImmTAC (IMCgp100) redirected CD8⁺ and CD4⁺ T cells

et al. 2017

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“…CD4 1 CD25 1 CD127 -/low T regs , a subpopulation of CD4 1 T cells, help to maintain immune homeostasis by inhibiting immune responses under physiological conditions [19]. Recently, emerging evidence indicated that the proportion of T regs is increased in various types of solid tumour, which is associated with poor prognosis [31]. However, the effect of CSCs on the recruitment of T regs remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated that tumour cells develop potent, overlapping mechanisms to foster immune privilege by including the infiltration of T regs into the tumour microenvironment [27][28][29][30]. T regs enriched in ovarian carcinoma lead to reduced survival [27] and this has also been observed in many other solid tumours, including melanomas, renal cancer, breast cancer, cervical cancer [31] and colorectal cancer [32]. T regs infiltrate into tumour sites via various mechanisms, such as trafficking, differentiation, expansion and conversion [33].…”

Section: Introductionmentioning

confidence: 99%

Ovarian cancer stem cells promote tumour immune privilege and invasion via CCL5 and regulatory T cells

You

et al. 2017

Clinical and Experimental Immunology

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SummaryEmerging evidence indicates a link between the increased proportion of regulatory T cells (T regs ) and reduced survival in patients who have been diagnosed with cancer. Cancer stem cells (CSCs) have been indicated to play a vital role in tumour initiation, drug resistance and recurrence. However, the relationship between T regs and CSCs remains largely unknown. Here, we sorted out ovarian cancer stem-like side population (SP) cells and CD133 1 cells to investigate the influence of ovarian CSCs on T regs . Among the various immune-related molecules that we assessed, C-C motif chemokine ligand 5 (CCL5) was the most elevated in ovarian CSCs relative to that in the non-CSCs. The expression of its receptor, C-C motif chemokine receptor 5 (CCR5), was also increased on the surface of T regs in ovarian cancer patients. This receptor-ligand expression profile indicated that ovarian CSCs recruit T regs via CCL5-CCR5 interactions. We further assessed the expression of interleukin (IL)-10 in T regs cultured with different cancer cells. For the first time, to our knowledge, our findings describe the relationship between ovarian CSCs and T regs , and demonstrated that these two cell populations co-operate to promote tumour immune tolerance and enhance tumour progression.

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“…Importantly, decreased ratios of tumor-infiltrating CD8 + T cells to FOXP3 + Treg cells were shown to correlate with poor prognosis, especially in patients with breast [51], gastric [46], and ovarian cancer [48,49]. Furthermore, a recent meta-analysis of previously published data indicated that in majority of solid tumors in the cervix, kidney, breast, and melanomas, high frequency of tumor-infiltrating FOXP3 + cells was significantly negatively correlated with patients' survival [52].…”

Section: Tumor-infiltrating Treg Cellsmentioning

confidence: 99%