A Toll-like receptor 2 agonist-fused antigen enhanced antitumor immunity by increasing antigen presentation and the CD8 memory T cells population
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Chiao-Chieh Wu1,2, Shih-Jen Liu2,3, Hsin-Wei Chen2,3, Kuan-Yin Shen2, Chih-Hsiang Leng1,2,3
1Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan
2National Institute of Infectious Disease and Vaccinology, National Health Research Institutes, Miaoli County 350, Taiwan
3Graduate Institute of Immunology, China Medical University, Taichung 40402, Taiwan
Chih-Hsiang Leng, email: [email protected]
Keywords: rlipo-immunogen, Toll-like receptor 2, antigen presentation, tumor regression, memory T cells
Received: October 21, 2015 Accepted: March 31, 2016 Published: April 26, 2016
The induction of long-lived effector CD8+ T cells is key to the development of efficient cancer vaccines. In this study, we demonstrated that a Toll-like receptor 2 (TLR2) agonist-fused antigen increased antigen presentation via TLR2 signaling and induced effector memory-like CD8+ T cells against cancer after immunization. The N-terminus of ovalbumin (OVA) was biologically fused with a bacterial lipid moiety TLR2 agonist to produce a recombinant lipidated ovalbumin (rlipo-OVA). We demonstrated that rlipo-OVA activated bone marrow-derived dendritic cells (BM-DCs) maturation and increased antigen presentation by major histocompatibility complex (MHC) class I via TLR2. After immunization, rlipo-OVA skewed the immune response towards T helper (Th) 1 and induced OVA-specific cytotoxic T lymphocyte (CTL) responses. Moreover, immunization with rlipo-OVA induced higher numbers of effector memory (CD44+CD62L−) CD8+ T cells compared with recombinant ovalbumin (rOVA) alone or rOVA mixed with the TLR2 agonist Pam3CSK4. Accordingly, the CD27+CD43+ effector memory CD8+ T cells expressed high levels of the long-lived CD127 marker. The administration of rlipo-OVA could inhibit tumor growth, but the anti-tumor effects were lost after the depletion of CD8 or CD127 cells in vivo. These findings suggested that the TLR2 agonist-fused antigen induced long-lived memory CD8+ T cells for efficient cancer therapy.
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