Intracellular bacterial vectors that induce CD8⁺ T cells with similar cytolytic abilities but disparate memory phenotypes provide contrasting tumor protection

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DOIResolve DOI: http://doi.org/10.1158/0008-5472.CAN-08-3160
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TypeArticle
Journal titleCancer Research
Volume69
Issue10
Pages43274334; # of pages: 8
AbstractInduction of a functional CD8⁺ T-cell response is the important criterion for cancer vaccines, and it is unclear whether acute or chronic live vectors are better suited for cancer antigen delivery. We have evaluated the tumor protective ability of two recombinant vectors, Listeria monocytogenes (LM) and Salmonella typhimurium (ST), both expressing ovalbumin (OVA). Although both vectors induced a similar OVA-specific CD8⁺ T-cell response in the long term, LM-OVA induced mainly central-phenotype (TCM, CD44highCD62Lhigh), whereas ST-OVA induced mainly effector- phenotype (TEM, CD44highCD62Llow) cells. Both vectors induced functional OVA-specific CD8⁺ T cells that expressed IFN-γ and killed targets specifically in vivo. However, only LMOVA– vaccinated mice were protected against B16-OVA tumors. This correlated to the ability of CD8⁺ T cells generated against LM-OVA, but not against ST-OVA, to produce interleukin 2 and exhibit profound homeostatic and antigen- induced proliferation in vivo. Furthermore, adoptive transfer of memory CD8⁺ T cells generated against LM-OVA (but not against ST-OVA) into recipient mice resulted in their trafficking to tumor-draining lymph nodes conferring protection. Although cytotoxicity and IFN-γ production are considered to be the principal functions of memory CD8⁺ T cells, the vaccine delivery strategy may also influence memory CD8⁺ Tcell quality, and ability to proliferate and traffic to tumors. Thus, for efficacy, cancer vaccines should be selected for their ability to induce self-renewing memory CD8⁺ T cells (CD44highIL-7RAhighCD62Lhigh) besides their effector functions.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Biological Sciences
Peer reviewedYes
NPARC number15314092
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Record identifierfcb83a6f-5ecb-4dd9-8555-22295a1b271d
Record created2010-05-17
Record modified2016-05-09
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