CD4CD25CD127 Treg and CD4CD45R0CD49bLAG3 Tr1 Cells in Bone Marrow and Peripheral Blood Samples from Children with Neuroblastoma

Overview

Journal Oncoimmunology

Specialty Allergy & Immunology

Date 2017 Jan 27

PMID 28123887

Citations 11

Authors

Fabio Morandi

Sarah Pozzi

Sebastiano Barco

Giuliana Cangemi

Loredana Amoroso

Barbara Carlini

Vito Pistoia

Maria Valeria Corrias

Affiliations

Soon will be listed here.

Abstract

Metastatic spread in the bone marrow (BM) at diagnosis is the worst prognostic factor for neuroblastoma (NB) patients. Here, we analyzed the presence of two immunosuppressive cell subsets, CD4CD25CD127 regulatory T (Treg) cells and CD4CD45R0CD49bLAG3 type 1 regulatory (Tr1) cells, in BM and peripheral blood (PB) samples from NB patients and controls. Frequency of both regulatory cell subsets was lower in BM and PB samples from NB patients than in respective healthy controls. No correlation was found between the frequency of Treg and Tr1 cells and prognostic factors at diagnosis, such as age and stage. Only amplification correlated to a higher number of Treg in BM and of Tr1 in PB. These findings suggested an altered trafficking of regulatory T cells in NB, but delineated a limited role of these subsets in BM microenvironment and/or periphery in NB. These observations should be considered designing immunotherapeutic approaches for metastatic NB.

Citing Articles

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References

Morandi F, Corrias M, Pistoia V . Evaluation of bone marrow as a metastatic site of human neuroblastoma. Ann N Y Acad Sci. 2014; 1335:23-31. DOI: 10.1111/nyas.12554. View

Tilak T, Sherawat S, Agarwala S, Gupta R, Vishnubhatla S, Bakhshi S . Circulating T-regulatory cells in neuroblastoma: a pilot prospective study. Pediatr Hematol Oncol. 2014; 31(8):717-22. DOI: 10.3109/08880018.2014.886002. View

Menetrier-Caux C, Gobert M, Caux C . Differences in tumor regulatory T-cell localization and activation status impact patient outcome. Cancer Res. 2009; 69(20):7895-8. DOI: 10.1158/0008-5472.CAN-09-1642. View

Brinkrolf P, Landmeier S, Altvater B, Chen C, Pscherer S, Rosemann A . A high proportion of bone marrow T cells with regulatory phenotype (CD4+CD25hiFoxP3+) in Ewing sarcoma patients is associated with metastatic disease. Int J Cancer. 2009; 125(4):879-86. DOI: 10.1002/ijc.24461. View

Gagliani N, Magnani C, Huber S, Gianolini M, Pala M, Licona-Limon P . Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells. Nat Med. 2013; 19(6):739-46. DOI: 10.1038/nm.3179. View

Morandi F, Croce M, Cangemi G, Barco S, Rigo V, Carlini B . IL-10 and ARG-1 concentrations in bone marrow and peripheral blood of metastatic neuroblastoma patients do not associate with clinical outcome. J Immunol Res. 2015; 2015:718975. PMC: 4417583. DOI: 10.1155/2015/718975. View

Mosse Y, Laudenslager M, Khazi D, Carlisle A, Winter C, Rappaport E . Germline PHOX2B mutation in hereditary neuroblastoma. Am J Hum Genet. 2004; 75(4):727-30. PMC: 1182065. DOI: 10.1086/424530. View

Gregori S, Goudy K, Roncarolo M . The cellular and molecular mechanisms of immuno-suppression by human type 1 regulatory T cells. Front Immunol. 2012; 3:30. PMC: 3342353. DOI: 10.3389/fimmu.2012.00030. View

Zou L, Barnett B, Safah H, LaRussa V, Evdemon-Hogan M, Mottram P . Bone marrow is a reservoir for CD4+CD25+ regulatory T cells that traffic through CXCL12/CXCR4 signals. Cancer Res. 2004; 64(22):8451-5. DOI: 10.1158/0008-5472.CAN-04-1987. View

10.

Cohn S, Pearson A, London W, Monclair T, Ambros P, Brodeur G . The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol. 2008; 27(2):289-97. PMC: 2650388. DOI: 10.1200/JCO.2008.16.6785. View

11.

Baecher-Allan C, Anderson D . Regulatory cells and human cancer. Semin Cancer Biol. 2005; 16(2):98-105. DOI: 10.1016/j.semcancer.2005.11.003. View

12.

Roychoudhuri R, Eil R, Restifo N . The interplay of effector and regulatory T cells in cancer. Curr Opin Immunol. 2015; 33:101-11. DOI: 10.1016/j.coi.2015.02.003. View

13.

Battaglia M, Gregori S, Bacchetta R, Roncarolo M . Tr1 cells: from discovery to their clinical application. Semin Immunol. 2006; 18(2):120-7. DOI: 10.1016/j.smim.2006.01.007. View

14.

Pinto N, Applebaum M, Volchenboum S, Matthay K, London W, Ambros P . Advances in Risk Classification and Treatment Strategies for Neuroblastoma. J Clin Oncol. 2015; 33(27):3008-17. PMC: 4567703. DOI: 10.1200/JCO.2014.59.4648. View

15.

Maris J, Matthay K . Molecular biology of neuroblastoma. J Clin Oncol. 1999; 17(7):2264-79. DOI: 10.1200/JCO.1999.17.7.2264. View

16.

Vicente D, Podesta M, Pitto A, Pozzi S, Lucchetti S, Lamparelli T . Progenitor cells trapped in marrow filters can reduce GvHD and transplant mortality. Bone Marrow Transplant. 2006; 38(2):111-7. DOI: 10.1038/sj.bmt.1705413. View

17.

Zhao E, Wang L, Dai J, Kryczek I, Wei S, Vatan L . Regulatory T cells in the bone marrow microenvironment in patients with prostate cancer. Oncoimmunology. 2012; 1(2):152-161. PMC: 3376984. DOI: 10.4161/onci.1.2.18480. View

18.

Chen J, Chen Z . The effect of immune microenvironment on the progression and prognosis of colorectal cancer. Med Oncol. 2014; 31(8):82. DOI: 10.1007/s12032-014-0082-9. View

19.

Gowda M, Godder K, Kmieciak M, Worschech A, Ascierto M, Wang E . Distinct signatures of the immune responses in low risk versus high risk neuroblastoma. J Transl Med. 2011; 9:170. PMC: 3195752. DOI: 10.1186/1479-5876-9-170. View

20.

Scaruffi P, Morandi F, Gallo F, Stigliani S, Parodi S, Moretti S . Bone marrow of neuroblastoma patients shows downregulation of CXCL12 expression and presence of IFN signature. Pediatr Blood Cancer. 2011; 59(1):44-51. DOI: 10.1002/pbc.23339. View