Research

Exosomes as a tumor immune escape mechanism: possible therapeutic implications

Thomas E Ichim^1,2,9 , Zhaohui Zhong^{* 3} , Shalesh Kaushal^{* 4} , Xiufen Zheng² , Xiubao Ren⁵ , Xishan Hao⁵ , James A Joyce⁶ , Harold H Hanley⁶ , Neil H Riordan¹ , James Koropatnick² , Vladimir Bogin¹ , Boris R Minev^7,8 , Wei-Ping Min² and Richard H Tullis⁶

¹Medistem Laboratories Inc, San Diego, USA

²Department of Surgery, Pathology, Oncology, Microbiology and Immunology, University of Western Ontario, London, Canada

³Department of Surgery, the Second Xiangya Hospital of Central South University, Changsha, PR China

⁴Department of Ophthalmology, University of Florida, Gainesville, USA

⁵Department of Surgery, Tianjin Medical University, Tianjin, PR China

⁶Aethlon Medical, San Diego, California, USA

⁷Moores UCSD Cancer Centre, San Diego, USA

⁸Division of Neurosurgery, University of California San Diego, San Diego, USA

⁹Medistem Laboratories, 9255 Towne Centre Drive, Suite 450, San Diego, California, 92122, USA

author email corresponding author email* Contributed equally

Journal of Translational Medicine 2008, 6:37doi:10.1186/1479-5876-6-37

Published:	22 July 2008

Abstract

Advances in cancer therapy have been substantial in terms of molecular understanding of disease mechanisms, however these advances have not translated into increased survival in the majority of cancer types. One unsolved problem in current cancer therapeutics is the substantial immune suppression seen in patients. Conventionally, investigations in this area have focused on antigen-nonspecific immune suppressive molecules such as cytokines and T cell apoptosis inducing molecules such as Fas ligand. More recently, studies have demonstrated nanovesicle particles termed exosomes are involved not only in stimulation but also inhibition of immunity in physiological conditions. Interestingly, exosomes secreted by cancer cells have been demonstrated to express tumor antigens, as well as immune suppressive molecules such as PD-1L and FasL. Concentrations of exosomes from plasma of cancer patients have been associated with spontaneous T cell apoptosis, which is associated in some situations with shortened survival. In this paper we place the "exosome-immune suppression" concept in perspective of other tumor immune evasion mechanisms. We conclude by discussing a novel therapeutic approach to cancer immune suppression by extracorporeal removal of exosomes using hollow fiber filtration technology