Relationship between CD4 Regulatory T Cells and Anergy In Vivo

Kalekar, Lokesh A.; Mueller, Daniel L.

doi:10.4049/jimmunol.1602031

Cited by 76 publications

(63 citation statements)

References 84 publications

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“…IL-6 and IL-23 can activate STAT3 signaling to promote tumor growth through autocrine or paracrine modes. On the other hand, overexpression of IL-23 can enhance the anti-tumor effect of CTLs by increasing the secretion of INF-γ [5]. Besides, the effect of IL-17 secreted by CD4 + lymphocytes on tumor T cells is also bidirectional [48, 49].…”

Section: Discussionmentioning

confidence: 99%

“…CD3 is a common differentiation antigen of mature T cells, expressed on the surface of mature T cells [4]. CD4 + T cells can promote the proliferation and differentiation of immune cells, and coordinate the interaction between immune cells [5]. CD8 + T cells are the main antitumor effector cells that kill tumor cells by releasing perforin or promoting apoptosis [6].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

Zheng¹,

Song

Shao

et al. 2018

Cell Physiol Biochem

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Background/Aims: Several studies have verified the correlation between tumor-infiltrating lymphocytes (TILs) and survival of patients with esophagus cancer (EC). However, the prognostic role of TILs is still controversial. Therefore, we performed this meta-analysis. Methods: We searched PubMed, Embase and the Cochrane Library (last update by August 30, 2017) to identify studies assessing the effect of TILs on survival of patients with EC. Pooled hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS) and cancer specific survival (CSS) were estimated using fixed-effects models or random-effects models, which depends on the heterogeneity. Results: Data from 22 observational studies including 2909 patients were summarized. Pooled analysis indicated that generalized TILs were favorable prognostic markers for OS in patients with EC (pooled HR = 0.48; 95% CI = 0.38-0.61; P < 0.001). For TIL subsets, CD8⁺ TILs were associated with improved OS (pooled HR = 0.68; 95% CI = 0.58–0.84; P < 0.001) and DFS (pooled HR = 0.90; 95% CI = 0.85-0.95; P < 0.001); FoxP3⁺ TILs were associated with patients’ DFS (pooled HR = 0.88; 95% CI = 0.81-0.96; P = 0.003). High CD57⁺ TILs indicated a better OS in patients with EC (pooled HR = 0.50; 95% CI = 0.35-0.72; P < 0.001). In addition, the pooled results showed that other TIL subsets including CD3⁺, CD4⁺ and CD45RO⁺ TILs were not associated with patients’ survival (P > 0.05). Conclusions: For patients with EC, some TIL subsets could serve as prognostic biomarkers. The application of TILs in the immunotherapy of EC needs to be verified through a large amount of clinical research.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

Zheng¹,

Song

Shao

et al. 2018

Cell Physiol Biochem

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“…In fact, several biological agents, including CTLA4 fusion proteins or anti-TNF antibodies 34 , have the ability to either induce an increase in number or the activity of Tregs. Treg function involves CD73 activity and other mechanisms of action 36 , 37 . Indeed, the importance of CD73 activity has been studied in a murine model of GvDH, demonstrating that the ectonuclease helps control the disease 30 .…”

Section: Discussionmentioning

confidence: 99%

The immunosuppressive effect of the tick protein, Salp15, is long-lasting and persists in a murine model of hematopoietic transplant

Tomás-Cortázar

Martín-Ruiz

Barriales

et al. 2017

Sci Rep

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Salp15, a salivary protein of Ixodes ticks, inhibits the activation of naïve CD4 T cells. Treatment with Salp15 results in the inhibition of early signaling events and the production of the autocrine growth factor, interleukin-2. The fate of the CD4 T cells activated in the presence of Salp15 or its long-term effects are, however, unknown. We now show that Salp15 binding to CD4 is persistent and induces a long-lasting immunomodulatory effect. The activity of Salp15 results in sustained diminished cross-antigenic antibody production even after interruption of the treatment with the protein. Transcriptionally, the salivary protein provokes an acute effect that includes known activation markers, such as Il2 or Cd44, and that fades over time. The long-term effects exerted by Salp15 do not involve the induction of either anergy traits nor increased populations of regulatory T cells. Similarly, the treatment with Salp15 does not result in B cell anergy or the generation of myeloid suppressor cells. However, Salp15 induces the increased expression of the ectoenzyme, CD73, in regulatory T cells and increased production of adenosine. Our study provides a profound characterization of the immunomodulatory activity of Salp15 and suggests that its long-term effects are due to the specific regulation of CD73.

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“…Furthermore, adenosine generated through NT5E was described to restrict inflammatory immune responses through a negative feedback loop on adenosine receptor expressing neutrophils ( 13 ). NT5E has been found expressed on regulatory T cells (T reg ) and at even higher levels on anergic CD4 + T cells, thereby preserving self tolerance in healthy individuals and protecting the fetus from maternal immune attack during pregnancy ( 14 , 15 ).…”

Section: Functions Of Nt5e In Healthy Tissue and Tumorsmentioning

confidence: 99%

Controlling the Immune Suppressor: Transcription Factors and MicroRNAs Regulating CD73/NT5E

2018

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The NT5E (CD73) molecule represents an ecto-5′-nucleotidase expressed on the cell surface of various cell types. Hydrolyzing extracellular adenosine monophosphate into adenosine and inorganic phosphate, NT5E performs numerous homeostatic functions in healthy organs and tissues. Importantly, NT5E can act as inhibitory immune checkpoint molecule, since free adenosine generated by NT5E inhibits cellular immune responses, thereby promoting immune escape of tumor cells. MicroRNAs (miRNAs) are small non-coding RNA molecules regulating gene expression on posttranscriptional level through binding to mRNAs, resulting in translational repression or degradation of the targeted mRNA molecule. In tumor cells, miRNA expression patterns are often altered which in turn might affect NT5E surface expression and eventually influence the efficacy of antitumor immune responses. This review describes the diverse roles of NT5E, summarizes current knowledge about transcription factors controlling NT5E expression, and highlights the significance of miRNAs involved in the posttranscriptional regulation of NT5E expression.

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Relationship between CD4 Regulatory T Cells and Anergy In Vivo

Cited by 76 publications

References 84 publications

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

The immunosuppressive effect of the tick protein, Salp15, is long-lasting and persists in a murine model of hematopoietic transplant

Controlling the Immune Suppressor: Transcription Factors and MicroRNAs Regulating CD73/NT5E

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