Abstract
Epstein-Barr virus (EBV)-related non-Hodgkin's lymphoma (NHL) represents a major problem in hematological clinical studies due to its drug tolerance and refractoriness. EBV infection is a key factor driving the process of tumor growth. Immune therapy is an important biotherapeutic method of treating cancer, which is attracting increasing attention. We hypothesized that combining conventional chemotherapy with immune therapy in the treatment of EBV-related NHL may achieve better outcomes. First, we successfully cloned large numbers of EBV-specific T cells by immune stimulation ex vivo. Subsequently, the combined therapy was applied in a murine model of human EBV-related NHL. As expected, combined therapy inhibited tumor growth more effectively compared with monotherapy. In addition, we continuously tested the tumor-associated immune microenvironment and observed that the numbers of tumor-infiltrating cytotoxic T lymphocytes (CTLs) and macrophages were elevated following combined therapy. These effects suggest that EBV-specific CTLs may indirectly promote an innate immune reaction in lymphoma by activating tumor-infiltrating macrophage proliferation. Our findings may provide a guide for the prospective treatment of EBV-related NHL.
References
Oct 1, 1996·Journal of Virology·B RehermannF V Chisari
Jun 3, 2000·Annual Review of Immunology·P C Doherty, J P Christensen
Mar 29, 2001·Experimental Hematology·B A NijmeijerJ H Falkenburg
Apr 6, 2001·The American Journal of Pathology·L GuedezW G Stetler-Stevenson
Apr 21, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·Z TabiL K Borysiewicz
Feb 28, 2002·Annual Review of Immunology·John H Russell, Timothy J Ley
Dec 31, 2002·Journal of Immunological Methods·Y SunB Autran
Aug 12, 2003·Oncogene·Bruce F Israel, Shannon C Kenney
Jul 17, 2004·Cancer Research·Michelle R StaudtDirk P Dittmer
Nov 24, 2005·Hematology·Helen E Heslop
Mar 23, 2006·Blood·Abel Sánchez-AguileraUNKNOWN Spanish Hodgkin Lymphoma Study Group
Jul 11, 2006·Blood·Joaquim CarrerasAlison H Banham
Dec 19, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Danielle CanioniLuc Xerri
Mar 5, 2008·Journal of Immunotherapy·Laszlo MarkaszLaszlo Szekely
Nov 3, 2009·Blood·Helen E HeslopCliona M Rooney
Mar 12, 2010·The New England Journal of Medicine·Christian SteidlRandy D Gascoyne
Apr 13, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Christian SteidlRandy D Gascoyne
Dec 6, 2011·Blood·Ekaterina DoubrovinaRichard J O'Reilly
Jul 26, 2012·Blood Cancer Journal·F MoriS Iida
Nov 22, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Vanya IchevaTobias Feuchtinger