Age-related increase of tumor susceptibility is associated with myeloid-derived suppressor cell mediated suppression of T cell cytotoxicity in recombinant inbred BXD12 mice

Grizzle, William E.; Xu, Xin; Zhang, Shuangqin; Stockard, Cecil R.; Liu, Cunren; Yu, Shaohua; Wang, Jianhua; Mountz, John D.; Zhang, Huang‐Ge

doi:10.1016/j.mad.2007.10.003

Cited by 102 publications

(81 citation statements)

References 44 publications

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“…As a result, starting at puberty, male mice invariably and progressively develop spontaneous mPIN (weeks [6][7][8][9][10][11][12] TRAMP mice and reached a plateau after week 20. However, a similar variability and increase was found also in age-matched WT animals, as previously reported by others in 12-month-old WT mice (42). We hypothesized that variability in disease stage in TRAMP mice of the same age could account for the variability in CD11b þ cells accrual.…”

Section: Modification Of Myelopoiesis In Tramp Mice Developing Spontasupporting

confidence: 87%

Modulators of Arginine Metabolism Do Not Impact on Peripheral T-Cell Tolerance and Disease Progression in a Model of Spontaneous Prostate Cancer

Rigamonti

Capuano

Ricupito

et al. 2011

Clinical Cancer Research

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Purpose: Chronic inflammation, recruitment of myeloid-derived cells, and perturbation of the arginine metabolism have been all proposed as mechanisms favoring prostate carcinogenesis and tumor immunoescape. Objective of this study was to evaluate whether accumulation of CD11b þ Gr1þ cells, also defined myeloid-derived suppressor cells, occur in mice affected by transplantable or spontaneous prostate cancer (PC). We also investigated whether N(G) nitro-L-arginine methyl ester (L-NAME) and sildenafil, both modulators of the arginine metabolism, restrain tumor growth and restore tumor-specific immunity.Experimental Design: Wild-type C57BL/6 mice bearing TRAMP-C1 PC and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were treated with vehicle, L-NAME or sildenafil, and evaluated for CD11b þ cells accumulation in the blood, several organs, and the tumor mass and for disease progression.organs and especially in the tumor of the two mouse models. L-NAME and sildenafil impaired the immunosuppressive function of CD11b þ cells in both models and restrained TRAMP-C1 growth, but they neither break tumor-specific immune tolerance nor limit tumor progression in TRAMP mice. Conclusions: Collectively, our results emphasize substantial differences in tumor-induced alteration of myelopoiesis and sensitivity to modulators of the arginine metabolism between a transplantable and a spontaneous model of PC. They also suggest that perturbation of the arginine metabolism is dispensable for PC progression and the associated T-cell tolerance.

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Section: Modification Of Myelopoiesis In Tramp Mice Developing Spontasupporting

confidence: 87%

Modulators of Arginine Metabolism Do Not Impact on Peripheral T-Cell Tolerance and Disease Progression in a Model of Spontaneous Prostate Cancer

Rigamonti

Capuano

Ricupito

et al. 2011

Clinical Cancer Research

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“…Reports are now emerging suggesting that increased frequency of MDSCs may play a role in the reduced immune surveillance of cancer. Grizzle et al (2007) showed that Gr1 + CD11b + MDSCs increased in the spleen from young (2-monthold) to mature (12-month-old) BXD12 mice. In the older mice, injected mammary adenocarcinoma (TS/A) cells became established, whereas in young animals, the tumour regressed 4 weeks after implantation.…”

Section: Cancer Mdscs and Ageingmentioning

confidence: 98%

Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease

Bueno

Sant’Anna

Lord

2014

AGE

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Infections, cancer and autoimmune diseases occur more frequently in the elderly, and although many factors contribute to this, the age-related remodelling of the immune system, termed immunosenescence, plays a major role. Over the last two decades, studies have evaluated the effect of ageing on both the adaptive and innate arms of the immune system and demonstrated compromised function in several cells including lymphocytes (naïve, effector and memory), regulatory T and B cells, monocytes, neutrophils and NK cells. In addition, a well-documented feature of ageing is the increase in systemic inflammatory status (inflammageing), with raised serum levels of IL6, TNFα and CRP as well as reduced IL10. Recently, myeloid-derived suppressor cells have been the focus of many reports as these cells show immunosuppressive properties and are present in higher frequency during infections, cancer and autoimmunity. Importantly, there have been publications showing increased numbers of myeloid-derived suppressor cells in aged mice and humans. In this review, we discuss the current literature on myeloid-derived suppressor cells, their possible role in altered immune function in the elderly, and whether it may be possible to manipulate these cells to alleviate age-related immune dysfunction.

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“…18 Purified T cells were cultured at 2 ϫ 10 6 /ml in RPMI 1640 medium containing 10% fetal calf serum, 2 mmol/L L-glutamine, 1 mmol/L sodium pyruvate, penicillin (100 U/ml), streptomycin (100 mg/ml), and 50 mol/L 2-mercaptoethanol in the presence of soluble anti-CD3 (2 g/ml clone; 145 2C11, BD Pharmingen, San Diego, CA) for 3 days. Then, B16 tumor cells were co-cultured with 3-day cultured spleen T cells (B16:spleen T cells ϭ 10:1) as described above for an additional 1 day.…”

Section: Co-culture Of B16 Tumor Cells With Cd3 Activated Spleen T Cellsmentioning

confidence: 99%

TLR2-Mediated Expansion of MDSCs Is Dependent on the Source of Tumor Exosomes

Xiang

Liu

Zhuang

et al. 2010

The American Journal of Pathology

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Exosomes released from tumor cells having been shown to induce interleukin-6 release from myeloidderived suppressor cells in a Toll-like receptor 2/Stat3-dependent manner. In this study, we show that exosomes released from tumor cells re-isolated from syngeneic mice are capable of inducing interleukin-6 in a Toll-like receptor 2-independent manner, whereas the data generated from exosomes of tumor cells having undergone numerous in vitro passages induce interleukin-6 in a Toll-like receptor 2-dependent manner. This discrepancy may be due to the source of tumor cells used to generate the exosomes for this study. These results suggest that exosomes released from tumor cells that are not within a tumor microenvironment may not realistically represent the role of tumor exosomes in vivo. This is an important consideration since frequently passing tumor cells in vivo is an accepted practice for studying tumor exosome-mediated inflammatory responses.

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Age-related increase of tumor susceptibility is associated with myeloid-derived suppressor cell mediated suppression of T cell cytotoxicity in recombinant inbred BXD12 mice

Cited by 102 publications

References 44 publications

Modulators of Arginine Metabolism Do Not Impact on Peripheral T-Cell Tolerance and Disease Progression in a Model of Spontaneous Prostate Cancer

Modulators of Arginine Metabolism Do Not Impact on Peripheral T-Cell Tolerance and Disease Progression in a Model of Spontaneous Prostate Cancer

Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease

TLR2-Mediated Expansion of MDSCs Is Dependent on the Source of Tumor Exosomes

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