American Association for Cancer Research
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Supplementary Figures 1 - 4 from PD-1 and Tim-3 Regulate the Expansion of Tumor Antigen–Specific CD8+ T Cells Induced by Melanoma Vaccines

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posted on 2023-03-30, 22:31 authored by Julien Fourcade, Zhaojun Sun, Ornella Pagliano, Joe-Marc Chauvin, Cindy Sander, Bratislav Janjic, Ahmad A. Tarhini, Hussein A. Tawbi, John M. Kirkwood, Stergios Moschos, Hong Wang, Philippe Guillaume, Immanuel F. Luescher, Arthur Krieg, Ana C. Anderson, Vijay K. Kuchroo, Hassane M. Zarour

PDF file - 292K, Supplementary Figure S1. Phenotype of vaccine-induced NY-ESO-1-specific CD4+ T cells. Supplementary Figure S2. Cytokine production, cytotoxic potential and cytolytic capacities of NY-ESO-1-specific CD8+ T cells following immunization in patients with spontaneous TA-specific CD8+ T cell responses before vaccination. Supplementary Figure S3. PD-1 and Tim-3 blockades increase the proliferation of vaccine-inducedNY-ESO-1-specific CD8+ T cells. Supplementary Figure S4. PD-1 and Tim-3 blockades increase the expansion of vaccine-induced cytokine-producing NY-ESO-1-specific CD8+ T cells.



Although melanoma vaccines stimulate tumor antigen–specific CD8+ T cells, objective clinical responses are rarely observed. To investigate this discrepancy, we evaluated the character of vaccine-induced CD8+ T cells with regard to the inhibitory T-cell coreceptors PD-1 and Tim-3 in patients with metastatic melanoma who were administered tumor vaccines. The vaccines included incomplete Freund's adjuvant, CpG oligodeoxynucleotide (CpG), and the HLA-A2–restricted analog peptide NY-ESO-1 157-165V, either by itself or in combination with the pan-DR epitope NY-ESO-1 119-143. Both vaccines stimulated rapid tumor antigen–specific CD8+ T-cell responses detected ex vivo, however, tumor antigen–specific CD8+ T cells produced more IFN-γ and exhibited higher lytic function upon immunization with MHC class I and class II epitopes. Notably, the vast majority of vaccine-induced CD8+ T cells upregulated PD-1 and a minority also upregulated Tim-3. Levels of PD-1 and Tim-3 expression by vaccine-induced CD8+ T cells at the time of vaccine administration correlated inversely with their expansion in vivo. Dual blockade of PD-1 and Tim-3 enhanced the expansion and cytokine production of vaccine-induced CD8+ T cells in vitro. Collectively, our findings support the use of PD-1 and Tim-3 blockades with cancer vaccines to stimulate potent antitumor T-cell responses and increase the likelihood of clinical responses in patients with advanced melanoma. Cancer Res; 74(4); 1045–55. ©2013 AACR.

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