TLR1/TLR2 agonist induces tumor regression by reciprocal modulation of effector and regulatory T cells

Zhang, Y., Luo, F., Cai, Y., Liu, N., Wang, L., Xu, D. and Chu, Y. (2011) TLR1/TLR2 agonist induces tumor regression by reciprocal modulation of effector and regulatory T cells. Journal of Immunology, 186(4), pp. 1963-1969. (doi: 10.4049/jimmunol.1002320) (PMID:21217015)

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Abstract

Using TLR agonists in cancer treatment can have either beneficial or detrimental effects. Therefore, it is important to determine their effect on the tumor growth and understand the underlying mechanisms in animal tumor models. In this study, we report a general immunotherapeutic activity of a synthetic bacterial lipoprotein (BLP), a TLR1/TLR2 agonist, on established lung carcinoma, leukemia, and melanoma in mice. Systemic treatment of 3LL tumor-bearing mice with BLP, but not LPS, led to a dose-dependent tumor regression and a long-lasting protective response against tumor rechallenge. The BLP-mediated tumor remission was neither mediated by a direct tumoricidal activity nor by innate immune cells, because it lacked therapeutic effect in immunodeficient SCID mice. Instead, BLP treatment reduced the suppressive function of Foxp3<sup>+</sup> regulatory T cells (Tregs) and enhanced the cytotoxicity of tumor-specific CTL in vitro and in vivo. Furthermore, adoptive cotransfer of BLP-pretreated but not untreated CTL and Tregs from wild-type but not from TLR2(-/-) mice was sufficient to restore antitumor immunity in SCID mice by reciprocally modulating Treg and CTL function. These results demonstrate that the TLR1/TLR2 agonist BLP may have a general tumor therapeutic property involving reciprocal downregulation of Treg and upregulation of CTL function. This property may play an important role in the development of novel antitumor strategies.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Xu, Dr Damo
Authors: Zhang, Y., Luo, F., Cai, Y., Liu, N., Wang, L., Xu, D., and Chu, Y.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Immunology
Journal Abbr.:J. Immunol.
Publisher:American Association of Immunologists
ISSN:0022-1767
ISSN (Online):1550-6606
Published Online:07 January 2011

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
241511Characterisation of genes differentially expressed on subsets of T lymphocytesFoo LiewMedical Research Council (MRC)G9818261Infection Immunity and Inflammation Medicine