Regulatory T Cells in Cancer

Mougiakakos, Dimitrios; Choudhury, Aniruddha; Lladser, Álvaro; Kiessling, Rolf; Johansson, C. Christian

doi:10.1016/s0065-230x(10)07003-x

Cited by 345 publications

(303 citation statements)

References 330 publications

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“…Evidence suggests that Tregs contribute to immune suppression by dampening the antitumor immunity elicited by CD4 + T cells, CD8 + T cells, dendritic and NK cells (24)(25)(26)(27). Treg accumulations in tumors and peripheral blood have been linked to unfavorable disease outcomes of tumor invasion, recurrence and shortened survival for many human solid tumors, including hepatocellular carcinoma, ovarian carcinoma, pancreatic ductal carcinoma, cervical cancer, NSCLC and breast cancer (28)(29)(30)(31)(32)(33). In these tumors, Tregs suppress antitumor immunity and mediate immune tolerance that favors tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

Wang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Previous studies have reported that regulatory T cells (Tregs), which are physiologically engaged in the maintenance of immunological self-tolerance, have a critical role in the regulation of the antitumor immune response. Targeting Tregs has the potential to augment cancer vaccine approaches. The current study therefore aimed to evaluate the role of cytokine-induced killer (CIK) cell infusion in modulating Tregs in patients with non-small cell lung cancer (NSCLC). A total of 15 patients with advanced NSCLC were treated by an infusion of CIK cells derived from autologous peripheral blood mononuclear cells (PBMCs). By using flow cytometry and liquid chip analysis, subsets of T cells and natural killer (NK) cells in peripheral blood, and plasma cytokine profiles in the treated patients, were analyzed at 2 and 4 weeks after CIK cell infusion. Cytotoxicity of PBMCs (n=15) and NK cells (n=6) isolated from NSCLC patients was evaluated before and after CIK cell therapy. Progression-free survival (PFS) and overall survival (OS) were also assessed. Analysis of the immune cell populations before and after treatment showed a significant increase in NK cells (P<0.05) concomitant with a significant decrease in Tregs (P<0.01) at 2 weeks post-infusion of CIK cells compared with the baseline. NK group 2D receptor (NKG2D) expression on NK cells was also significantly increased at 2 weeks post-infusion compared with the baseline (P<0.05). There was a positive correlation between NKG2D expression and the infusion number of CIK cells (P<0.05).

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Section: Discussionmentioning

confidence: 99%

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

Wang

et al. 2017

Experimental and Therapeutic Medicine

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“…In humans, defects in FOXP3 induce a generalized autoimmune disorder called immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX), a rare, early onset, disease affecting males and manifesting with severe enlargement of the secondary lymphoid organs, insulin dependent diabetes, eczema, food allergies, and infections. Mice bearing a spontaneous mutation in Foxp3, which are known as "scurfy", manifest a very similar disorder [1,8]. Foxp3 is consider as a specific marker of Tregs in mice but, in humans, activated T cells can transiently expressed it.…”

Section: Regulatory T Cell Subsetsmentioning

confidence: 99%

“…However, as the malignant lesions grow, such immune responses virtually vanish, mostly due to the multipronged immunosuppressive network that develops in the tumor microenvironment [1,2].…”

Section: Introductionmentioning

confidence: 99%

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

Tanchot

Terme

Péré

et al. 2012

Cancer Microenvironment

117

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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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“…CD4 + CD25 + Tregs expressing the transcription factor Foxp3 inhibit autoimmune responses and promote tumor progression (13,14). Accordingly, the depletion of Tregs results in improved antitumor immune responses and delays tumor growth in many tumor models (15).…”

mentioning

confidence: 99%

Tumor-Infiltrating Monocytic Myeloid-Derived Suppressor Cells Mediate CCR5-Dependent Recruitment of Regulatory T Cells Favoring Tumor Growth

Schlecker

Stojanović

Eisen

et al. 2012

The Journal of Immunology

350

273

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Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of myeloid cells in cancer patients and tumor-bearing mice that potently inhibits T cell responses. During tumor progression, MDSCs accumulate in several organs, including the tumor tissue. So far, tumor-infiltrating MDSC subpopulations remain poorly explored. In this study, we performed global gene expression profiling of mouse tumor-infiltrating granulocytic and monocytic (MO-MDSC) subsets compared with MDSCs from peripheral blood. RMA-S lymphoma–infiltrating MO-MDSCs not only produced high levels of NO and arginase-1, but also greatly increased levels of chemokines comprising the CCR5 ligands CCL3, CCL4, and CCL5. MO-MDSCs isolated from B16 melanoma and from skin tumor–bearing ret transgenic mice also expressed high levels of CCL3, CCL4, and CCL5. Expression of CCR5 was preferentially detected on regulatory T cells (Tregs). Accordingly, tumor-infiltrating MO-MDSCs directly attracted high numbers of Tregs via CCR5 in vitro. Intratumoral injection of CCL4 or CCL5 increased tumor-infiltrating Tregs, and deficiency of CCR5 led to their profound decrease. Moreover, in CCR5-deficient mice, RMA-S and B16 tumor growth was delayed emphasizing the importance of CCR5 in the control of antitumor immune responses. Overall, our data demonstrate that chemokines secreted by tumor-infiltrating MO-MDSCs recruit high numbers of Tregs revealing a novel suppressive role of MDSCs with potential clinical implications for the development of cancer immunotherapies.

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Regulatory T Cells in Cancer

Cited by 345 publications

References 330 publications

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

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

Tumor-Infiltrating Monocytic Myeloid-Derived Suppressor Cells Mediate CCR5-Dependent Recruitment of Regulatory T Cells Favoring Tumor Growth

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