Tumor Antigen-Specific FOXP3+ CD4 T Cells Identified in Human Metastatic Melanoma: Peptide Vaccination Results in Selective Expansion of Th1-like Counterparts

被引：35

作者：

Jandus, Camilla ^{[1
]}

Bioley, Gilles ^{[1
]}

Dojcinovic, Danijel ^{[4
]}

Derre, Laurent ^{[1
]}

Baitsch, Lukas ^{[1
]}

Wieckowski, Sebastien ^{[2
]}

Rufer, Nathalie ^{[2
]}

Kwok, William W. ^{[5
]}

Tiercy, Jean-Marie ^{[6
]}

Luescher, Immanuel F. ^{[4
]}

Speiser, Daniel E. ^{[1
,3
]}

Romero, Pedro ^{[1
,3
]}

机构：

[1] Hop Orthoped, Ludwig Inst Canc Res Ltd, Div Clin Oncoimmunol, Lausanne Branch, CH-1011 Lausanne, Switzerland

[2] Univ Lausanne, CHUV, Fac Biol & Med, Dept Res, Lausanne, Switzerland

[3] Ludwig Inst Canc Res Ltd, Lausanne Branch, Natl Ctr Competence Res, Epalinges, Switzerland

[4] Ludwig Inst Canc Res Ltd, Lausanne Branch, Mol Immunol Grp, Epalinges, Switzerland

[5] Virginia Mason, Benaroya Res Inst, Seattle, WA USA

[6] Univ Hosp Geneva, Div Immunol & Allergol, Transplantat Immunol Unit, Natl Reference Lab Histocompatibil, Geneva, Switzerland

来源：

CANCER RESEARCH | 2009年 / 69卷 / 20期

关键词：

EX-VIVO CHARACTERIZATION; REPLICATIVE HISTORY; CANCER-PATIENTS; CD8+T CELLS; MHC CLASS; CD8(+); RESPONSES; LYMPHOCYTES; IMMUNOTHERAPY; EPITOPE;

D O I：

10.1158/0008-5472.CAN-09-2226

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We have previously shown that vaccination of HLA-A2 metastatic melanoma patients with the analogue Melan-A(26-35(A27L)) peptide emulsified in a mineral oil induces; ex vivo detectable specific CD8 T cells. These are further enhanced when a TLR9 agonist is codelivered in the same vaccine formulation. Interestingly, the same peptide can be efficiently recognized by HLA-DQ6-restricted CD4 T cells. We use HLA-DQ6 multimers to assess the specific CD4 T-cell response in both healthy individuals and melanoma patients. We report that the majority of melanoma patients carry high frequencies of naturally circulating HLA-DQ6-restricted Melan-A-specilic CD4 T cells, a high proportion of which express FOXP3 and proliferate poorly in response to the cognate peptide. Upon vaccination, the relative frequency of multimer+ CD4 T cells did not change significantly. In contrast, we found a marked shift to FOXP3-negative CD4 T cells, accompanied by robust CD4 T-cell proliferation upon in vitro stimulation with cognate peptide. A concomitant reduction in TCR diversity was also observed. This is the first report on direct ex vivo identification of antigen-specific FOXP3+ T cells by multimer labeling in cancer patients and on the direct assessment of the impact of peptide vaccination on immunoregulatory T cells. [Cancer Res 2009;69(20):8085-93]

引用

页码：8085 / 8093

页数：9