Mechanistic insights into extracorporeal photochemotherapy: efficient induction of monocyte-to-dendritic cell maturation

Richard L Edelson, Richard L Edelson

Abstract

Extracorporeal photochemotherapy (ECP) is a widely used immunotherapy for cutaneous T cell lymphoma, as well as immunomodulation of graft-versus-host disease (GVHD) and transplanted organ rejection. ECP's mechanism encompasses large-scale physiologic platelet induction of dendritic cells (DCs). The normal bidirectional immunologic talents of DCs likely contribute heavily to ECP's capacity to immunize against tumor antigens, while also suppressing transplant immunopathology. Our understanding of how ECP physiologically induces monocyte-to-DC maturation can enhance the treatment's potency, potentially broaden its use to other cancers and autoimmune disorders and tailor its application to individual patients' diseases. ECP's next decade is filled with promise.

Keywords: Antigen-presenting cells; Cancer; Dendritic cells; Photopheresis; Tolerance.

Copyright © 2013 Elsevier Ltd. All rights reserved.

Figures

Fig. 1. Platelet driven monocyte-to-dendritic cell maturation
Fig. 1. Platelet driven monocyte-to-dendritic cell maturation
Physiologic interactions between ECP-processed monocytes and ECP-activated platelets induce the monocytes to commence differentiation into DC. Firm binding of passaged platelets, via three receptor-ligand interactions, activate the platelets to instantaneously transport preformed P-selectin and fibronectin to their surface. (A) After plasma fibrinogen coats the UVA transparent plastic surface of the flow chamber, passaged platelets (via their αIIb chain) bind to the γ-chain of immobilized plastic-fibrinogen. (B) Through their αIIbβ3 and α5β1 receptors, platelets bind to repetitive RGD tripeptides of plastic-immobilized fibrinogen. (C) P-selectin on now activated platelets transients binds PSGL-1 on the surface of passaged monocytes, activating the monocytes and resulting in integrin receptor conformational changes. (D) Partially-activated monocytes, via their reconfigured integrin receptors, adhere to additional platelet-expressed ligands, including RGD domains of platelet fibronectin. (E) via these activation signals, monocytes are induced to enter the DC maturational pathway. PUVA, while not involved in any of these interactions, contributes to monocyte differentiation, through secondary uptake of PUVA-induced apoptotic lymphocytes, which are far more sensitive to PUVA than are monocytes.

References

    1. Edelson R, Berger C, Gasparro F, Jegasothy B, Heald P, Wintroub B, et al. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med. 1987;316:297–303.
    1. Heald P, Rook A, Perez M, Wintroub B, Knobler R, Jegasothy B, et al. Treatment of erythrodermic cutaneous T-cell lymphoma with extracorporeal photochemotherapy. J Amer Acad Dermatol. 1992;17:427–433.
    1. Lutzner M, Edelson R, Schein P, Green I, Kirkpatrick C, Ahmed A. Cutaneous T-cell lymphomas: the Sézary syndrome, mycosis fungoides, and related disorders. Ann Intern Med. 1975;83:534–552.
    1. Edelson R, Facktor M, Andrews A, Lutzner M, Schein P. Successful management of the Sezary syndrome. Mobilization and removal of extravascular neoplastic T cells by leukapheresis. N Engl J Med. 1974;291:293–294.
    1. Edelson R, Brown J, Grossman M, Hardy M. Anti-thymocyte globulin in treatment of T-cell lymphoma. Lancet. 1977;8031:249–250.
    1. Yemul S, Berger C, Estabrook A, Suarez S, Edelson R, Bayley H. Selective killing of T lymphocytes by phototoxic liposomes. Proc Natl Acad Sci. 1987;84:246–250.
    1. Santella R, Dharmaraja N, Gasparro F, Edelson R. Monoclonal antibodies to DNA modified by 8-methoxypsoralen and ultraviolet A light. Nucl Acids Res. 1985;13:2533–2544.
    1. Greinix H, Knobler R, editors. Extracorporeal Photoimmunotherapy. First edition. Berlin/Boston: Walter de Gruyter GambH & Co. KG; 2012. pp. 1–215.
    1. Andreu G, Leon A, Heshmati F, Tod M, Menkes C, Baudelot J. Extracorporeal photochemotherapy: evaluation of two techniques and use in connective tissue disorders. Transf Sci. 1994;15:443–454.
    1. Heshmati F. Extracorporeal photochemotherapy (ECP) in acute and chronic GVHD. Transf Apheresis Sci. 2010;43:211–215.
    1. Pierelli L, Perseghin P, Marchetti M, Messina C, Perotti C, Mazzoni A, et al. Extracorporeal photopheresis for the treatment of acute and chronic graft-versus-host disease in adults and children: best practice recommendations from an Italian Society of Hemapheresis and Cell Manipulation (SIdEM) and Italian Group for Bone Marry Transplantation (GITMO) consensus process. Transfusion. 2013 Jan;10 [Epub ahead of print].
    1. Berger C, Longley B, Imaeda S, Christensen I, Heald P, Edelson R. Tumor-specific peptides in cutaneous T-cell lymphoma: association with class I major histocompatibility complex and possible derivation from the clonotypic T-cell receptor. Int J Cancer. 1998;76:304–311.
    1. Barr M, Meiser B, Eisen H, Roberts R, Livi U, Dall’amico R, et al. Photopheresis for the prevention of rejection in cardiac transplantation. Photopheresis transplantation study group. N Engl J Med. 1998;339:1744–1751.
    1. Greinix H, van Besien K, Elmaagacli A, Hillen U, Grigg A, Knobler R, et al. Progressive improvement in cutaneous and extracutaneous chronic graft-versus-host disease after a 24-week course of extracorporeal Photopheresis – results of a crossover randomized study. Biol Blood Marrow Transplant. 2011;17:1775–1782.
    1. Albert M, Sauter B, Bhardwaj N. Dendritic cells acquire antigen from apoptotic cells and induce class I restricted CTLs. Nature. 1998;392:86–89.
    1. Perez M, Berger C, Yamane Y, John L, Laroche L, Edelson R. Inhibition of anti-skin allograft immunity induced by infusions with photoinactivated effector T lymphocytes – the congenic model. Transplantation. 1991;51:1283–1289.
    1. Laroche L, Edelson R, Perez M, Berger C. Antigen-specific tolerance induced by autoimmunization with photoinactivated syngeneic effector cells. Ann NY Acad Sci. 1991;636:113–123.
    1. Schwartz L, Ashwell J, editors. Methods in Cell Biology. San Diego/London: Academic Press; 2001. [Apoptosis].
    1. Maeda A, Schwarz A, Bullinger A, Morita A, Peritt D, Schwarz T. Experimental extracorporeal photopheresis inhibits the sensitization and effector phases of contact hypersensitivity via two mechanisms: generation of IL-10 and induction T regulatory cells. J Immunol. 2008;181:5956–5962.
    1. Berger C, Hoffmann K, Vasquez J, Mane S, Lewis J, Filler R, et al. Rapid generation of maturationally synchronized human dendritic cells: contribution to the clinical efficacy of extracorporeal photochemotherapy. Blood. 2010;116:4838–4847.
    1. Girardi M, Berger C, Wilson L, Christensen I, Thompson K, Glusac E, et al. Transimmunization for cutaneous T cell lymphoma: a Phase I study. Leuk Lymphoma. 2006;47:1495–1503.
    1. Gilboa E. The promise of cancer vaccines. Nat Rev Cancer. 2004;4:401–411.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever