ORIGINAL ARTICLES   

Minerva Biotecnologica 1999 March;11(1):1-6

Copyright © 1999 EDIZIONI MINERVA MEDICA

language: English

Human cytotoxic T lymphocyte responses to Epstein-Barr virus (EBV). Implications for immunotherapy of EBV-Associated malignancies

Gavioli R.

Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy

Epstein-Barr ­virus (EBV) is a wide­spread lym­pho­trop­ic ­herpes ­virus ­which caus­es infec­tious mono­nu­cle­o­sis, and is asso­ciat­ed ­with an increas­ing num­ber of ­human malig­nan­cies. This ­broad dis­ease asso­ci­a­tion is in ­sharp con­trast to the ­spread of the ­virus in all ­human pop­u­la­tions and its capac­ity to per­sist as a ­life-­long asymp­to­mat­ic infec­tion. EBV induc­es ­long-last­ing cyto­tox­ic T-lym­pho­cyte (CTL) mem­o­ry, ­which is ­believed to ­play an impor­tant ­role in con­trol­ling EBV-car­ry­ing ­cells in the infect­ed ­host. The dem­on­stra­tion ­that the immu­no­blas­tic lym­pho­mas occur­ring in immu­no­sup­pressed indi­vid­u­als rep­re­sent the in ­vivo out­growth of EBV-pos­i­tive LCL-­like ­cells empha­siz­es the ­role of ­immune sur­veil­lance in con­trol­ling ­this poten­tial­ly lym­phom­a­gen­ic ­virus. Indeed, EBV-spe­cif­ic CTL-­based treat­ments ­have ­been suc­cess­ful­ly ­applied in var­i­ous cas­es of immu­no­blas­tic B-­cell lym­pho­mas, in ­severe chron­ic ­active EBV-infec­tion, and ­more recent­ly in HD. The ­results of ­these stud­ies sug­gest ­that an anti­gen-spe­cif­ic CTL-­based ther­a­py may be of ben­e­fit in treat­ing EBV-asso­ciat­ed ­tumors ­such as NPC and HD ­that, ­among the immu­no­gen­ic EBV-anti­gens, ­express exclu­sive­ly LMP1 and LMP2. NPC and HD are not asso­ciat­ed ­with sig­nif­i­cant immu­no­sup­pres­sion, imply­ing ­that ­escape ­from EBV-spe­cif­ic immu­nity may ­play an impor­tant ­role in the devel­op­ment of ­these ­tumors. Tumor-­escape may be ­ascribed to the low immu­nog­e­nic­ity of the epi­topes, ­since sub­dom­i­nant epi­topes ­could be inef­fi­cient in trig­ger­ing CTL respons­es ade­quate to con­trol the ­growth of EBV-pos­i­tive malig­nant ­cells in ­vivo. The trans­for­ma­tion of sub­dom­i­nant epi­topes in “improved epi­topes” may rep­re­sent a strat­e­gy to ­enhance stim­u­la­tion of nat­u­ral epi­tope-spe­cif­ic CTL respons­es, and ­could ­prove use­ful for CTL-­based immu­noth­e­ra­pies.