Depletion of CD25+ T cells from hematopoietic stem cell grafts increases posttransplantation vaccine-induced immunity to neuroblastoma

Jing, Weiqing; Yan, Xiaocai; Hallett, William; Gershan, Jill A.; Johnson, Bryon D.

doi:10.1182/blood-2010-12-326108

Cited by 40 publications

(35 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During immune priming, CD4 activity is dominated by helper function. Although it has been reported that CD4 cells are not required for priming, they are required for effective CD8 memory formation (32)(33)(34). CD8 memory cells formed in the absence of CD4 cells had an exhausted phenotype and increased PD-1 expression (32,34).…”

Section: Discussionmentioning

confidence: 99%

Foxp3+ T Cells Inhibit Antitumor Immune Memory Modulated by mTOR Inhibition

et al. 2014

View full text Add to dashboard Cite

Inhibition of mTOR signaling enhances antitumor memory lymphocytes. However, pharmacologic mTOR inhibition also enhances regulatory T-cell (Treg) activity. To counter this effect, Treg control was added to mTOR inhibition in preclinical models. Tregs were controlled with CD4-depleting antibodies because CD4 depletion has high translational potential and already has a well-established safety profile in patients. The antitumor activity of the combination therapy was CD8 dependent and controlled growth of syngeneic tumors even when an adoptive immunotherapy was not used. Lymphocytes resulting from the combination therapy could be transferred into na€ ve mice to inhibit aggressive growth of lung metastases. The combination therapy enhanced CD8 memory formation as determined by memory markers and functional studies of immune recall. Removal of FoxP3-expressing T lymphocytes was the mechanism underlying immunologic memory formation following CD4 depletion. This was confirmed using transgenic DEREG (depletion of regulatory T cells) mice to specifically remove Foxp3 þ T cells. It was further confirmed with reciprocal studies where stimulation of immunologic memory because of CD4 depletion was completely neutralized by adoptively transferring tumor-specific Foxp3 þ T cells. Also contributing to tumor control, Tregs that eventually recovered following CD4 depletion were less immunosuppressive. These results provide a rationale for further study of mTOR inhibition and CD4 depletion in patients. Cancer Res; 74(8); 2217-28. Ó2014 AACR.

show abstract

Section: Discussionmentioning

confidence: 99%

Foxp3+ T Cells Inhibit Antitumor Immune Memory Modulated by mTOR Inhibition

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Several clinical trials are underway investigating their therapeutic properties [166]. Targeting Tregs by anti-CD25 antibodies showed inhibition of neuroblastoma tumors in mice [167]. There are also data demonstrating that activation of the signal transducer and activator of transcription (STAT)3 signaling pathway supports tumor development by inducing accumulations of MDSCs and inhibition of DC differentiation [168]; hence its inactivation leads to inhibition of cancer development by a DC-and Treg-dependent mechanism [169].…”

Section: Molecular Targetsmentioning

confidence: 97%

Immune evasion in cancer: Mechanistic basis and therapeutic strategies

Vinay

Ryan

Pawelec

et al. 2015

Seminars in Cancer Biology

1,248

865

View full text Add to dashboard Cite

Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are a number of factors that contribute to tumor persistence despite having a normal host immune system. Immune editing is one of the key aspects why tumors evade surveillance causing the tumors to lie dormant in patients for years through "equilibrium" and "senescence" before re-emerging. In addition, tumors exploit several immunological processes such as targeting the regulatory T cell function or their secretions, antigen presentation, modifying the production of immune suppressive mediators, tolerance and immune deviation. Besides these, tumor heterogeneity and metastasis also play a critical role in tumor growth. A number of potential targets like promoting Th1, NK cell, γδ T cell responses, inhibiting Treg functionality, induction of IL-12, use of drugs including phytochemicals have been designed to counter tumor progression with much success. Some natural agents and phytochemicals merit further study. For example, use of certain key polysaccharide components from mushrooms and plants have shown to possess therapeutic impact on tumor-imposed genetic instability, anti-growth signaling, replicative immortality, dysregulated metabolism etc. In this review, we will discuss the advances made toward understanding the basis of cancer immune evasion and summarize the efficacy of various therapeutic measures and targets that have been developed or are being investigated to enhance tumor rejection.

show abstract

“…In contrast to the multipronged vaccination strategy used here, those studies required tumor cell vaccination after de novo T-cell genesis following transplant, higher doses of donor T cells (.2.0 3 10 6 ), or presensitization of donor T cells with the tumor vaccine. [67][68][69] One objective of our study was to rapidly elicit T-cell responses by transplanted donor cells prior to de novo production of thymic-derived T cells. Expansion of donor tumor-reactive CD8…”

Section: Discussionmentioning

confidence: 99%