title: PD-1 expression on dendritic cells suppresses CD8+T cell function and antitumor immunity.
abstract: Programmed death one (PD-1) is a well-established co-inhibitory regulator that suppresses proliferation and cytokine production of T cells. Despite remarkable progress in delineating the functional roles of PD-1 on T lymphocytes, little is known about the regulatory role of PD-1 expressed on myeloid cells such as dendritic cells (DCs). Here, we show that CD8+T cells can be more potently activated to secrete IL-2 and IFNγ by PD-1-deficient DCs compared to wild-type DCs. Adoptive transfer of PD-1-deficient DCs demonstrated their superior capabilities in inducing antigen-specific CD8+T cell proliferationin vivo. In addition, we provide first evidence demonstrating the existence of peripheral blood DCs and CD11c+tumor-infiltrating myeloid cells that co-express PD-1 in patients with hepatocellular carcinoma (HCC). The existence of PD-1-expressing HCC-infiltrating DCs (HIDCs) was further supported in a mouse model of HCC. Intratumoral transfer of PD-1-deficient DCs rendered recipient mice resistant to the growth of HCC by promoting tumor-infiltrating CD8+effector T cells to secrete perforin and granzyme B. This novel finding provides a deeper understanding of the role of PD-1 in immune regulation and has significant implications for cancer immunotherapies targeting PD-1.
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), 8A Biomedical Grove, IMMUNOS Building #4, BIOPOLIS, Singapore; A. Menarini Biomarkers Singapore Pte Ltd, 30 Pasir Panjang Road, #08-32, Mapletree Business City, Singapore.
authors.forename: Tong Seng
authors.initials: TS
authors.lastname: Lim
authors.affiliation: SingHealth Translational Immunology and Inflammation Center (STIIC), Duke-NUS Medical School, The Academia , 20 College Road, Discovery Tower Level 8 , Singapore.
authors.forename: Valerie
authors.initials: V
authors.lastname: Chew
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR) , 8A Biomedical Grove, IMMUNOS Building #4, BIOPOLIS , Singapore.
authors.forename: Je Lin
authors.initials: JL
authors.lastname: Sieow
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR) , 8A Biomedical Grove, IMMUNOS Building #4, BIOPOLIS , Singapore.
authors.forename: Siting
authors.initials: S
authors.lastname: Goh
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), 8A Biomedical Grove, IMMUNOS Building #4, BIOPOLIS, Singapore; Department of Pathology, Singapore General Hospital, 20 College Road, Academia, Diagnostics Tower, Singapore.
authors.forename: Joe Poh-Sheng
authors.initials: JP
authors.lastname: Yeong
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR) , 8A Biomedical Grove, IMMUNOS Building #4, BIOPOLIS , Singapore.
authors.forename: Ai Ling
authors.initials: AL
authors.lastname: Soon
authors.affiliation: Genomics, Genetics and Biology Innovation Pole (PoloGGB), Piazza Gambuli, Edificio D, 3° Piano, Perugia, Italy; A. Menarini Biomarkers Singapore Pte Ltd, 30 Pasir Panjang Road, #08-32, Mapletree Business City, Singapore.
authors.forename: Paola
authors.initials: P
authors.lastname: Ricciardi-Castagnoli
keywords: Antitumor immunity; Programmed death one (PD-1); cancer immunotherapy; dendritic cell; hepatocellular carcinoma; liver cancer