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Open Access 01-12-2016 | Original Article

Blockade of programmed death-1/programmed death ligand pathway enhances the antitumor immunity of human invariant natural killer T cells

Authors: Toshiko Kamata, Akane Suzuki, Naoko Mise, Fumie Ihara, Mariko Takami, Yuji Makita, Atsushi Horinaka, Kazuaki Harada, Naoki Kunii, Shigetoshi Yoshida, Ichiro Yoshino, Toshinori Nakayama, Shinichiro Motohashi

Published in: Cancer Immunology, Immunotherapy | Issue 12/2016

Abstract

The role of invariant natural killer T (iNKT) cells in antitumor immunity has been studied extensively, and clinical trials in patients with advanced cancer have revealed a prolonged survival in some cases. In recent years, humanized blocking antibodies against co-stimulatory molecules such as PD-1 have been developed. The enhancement of T cell function is reported to improve antitumor immunity, leading to positive clinical effects. However, there are limited data on the role of PD-1/programmed death ligand (PDL) molecules in human iNKT cells. In this study, we investigated the interaction between PD-1 on iNKT cells and PDL on antigen-presenting cells (APCs) in the context of iNKT cell stimulation. The blockade of PDL1 at the time of stimulation resulted in increased release of helper T cell (Th) 1 cytokines from iNKT cells, leading to the activation of NK cells. The direct antitumor function of iNKT cells was also enhanced after stimulation with anti-PDL1 antibody-treated APCs. According to these results, we conclude that the co-administration of anti-PDL1 antibody and alpha-galactosylceramide (αGalCer)-pulsed APCs enhances iNKT cell-mediated antitumor immunity.

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Kawano T, Koezuka Y, Toura I et al (1997) CD1d-restricted and TCR-mediated activation of Vα14 NKT cells by glycosylceramides. Science 278:1626–1629. doi:10.1126/science.278.5343.1626 CrossRefPubMed

Vivier E, Ugolini S, Blaise D, Chabannon C, Brossay L (2012) Targeting natural killer cells and natural killer T cells in cancer. Nat Rev Immunol 12:239–252. doi:10.1038/nri3174 CrossRefPubMed

Taniguchi M, Seino K, Nakayama T (2003) The NKT cell system: bridging innate and acquired immunity. Nat Immunol 4:1164–1165. doi:10.1038/ni1203-1164 CrossRefPubMed

Fujii S, Motohashi S, Shimizu K, Nakayama T, Yoshiga Y, Taniguchi M (2010) Adjuvant activity mediated by iNKT cells. Semin Immunol 22:97–102. doi:10.1016/j.smim.2009.10.002 CrossRefPubMed

Konishi J, Yamazaki K, Yokouchi H, Shinagawa N, Iwabuchi K, Nishimura M (2004) The characteristics of human NKT cells in lung cancer-CD1d independent cytotoxicity against lung cancer cells by NKT cells and decreased human NKT cell response in lung cancer patients. Hum Immunol 65:1377–1388. doi:10.1016/j.humimm.2004.09.003 CrossRefPubMed

Motohashi S, Nakayama T (2008) Clinical applications of natural killer T cell-based immunotherapy for cancer. Cancer Sci 99:638–645. doi:10.1111/j.1349-7006.2008.00730.x CrossRefPubMed

Motohashi S, Nakayama T (2009) Invariant natural killer T cell-based immunotherapy for cancer. Immunotherapy 1:73–82. doi:10.2217/1750743X.1.1.73 CrossRefPubMed

Motohashi S, Okamoto Y, Yoshino I, Nakayama T (2011) Anti-tumor immune responses induced by iNKT cell-based immunotherapy for lung cancer and head and neck cancer. Clin Immunol 140:167–176. doi:10.1016/j.clim.2011.01.009 CrossRefPubMed

Shiao SL, Ganesan AP, Rugo HS, Coussens LM (2011) Immune microenvironments in solid tumors: new targets for therapy. Genes Dev 25:2559–2572. doi:10.1101/gad.169029.111 CrossRefPubMedPubMedCentral

10.

Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9:162–174. doi:10.1038/nri2506 CrossRefPubMedPubMedCentral

11.

Flavell RA, Sanjabi S, Wrzesinski SH, Licona-Limon P (2010) The polarization of immune cells in the tumour environment by TGFβ. Nat Rev Immunol 10:554–567. doi:10.1038/nri2808 CrossRefPubMed

12.

Nishikawa H, Sakaguchi S (2010) Regulatory T cells in tumor immunity. Int J Cancer 127:759–767. doi:10.1002/ijc.25429 PubMed

13.

Okazaki T, Chikuma S, Iwai Y, Fagarasan S, Honjo T (2013) A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application. Nat Immunol 14:1212–1218. doi:10.1038/ni.2762 CrossRefPubMed

14.

Ribas A (2012) Tumor immunotherapy directed at PD-1. N Engl J Med 366:2517–2519CrossRefPubMed

15.

Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N (2002) Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA 99:12293–12297. doi:10.1073/pnas.192461099 CrossRefPubMedPubMedCentral

16.

Brahmer JR, Tykodi SS, Chow LQ et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465. doi:10.1056/NEJMoa1200694 CrossRefPubMedPubMedCentral

17.

Topalian SL, Hodi FS, Brahmer JR et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443–2454. doi:10.1056/NEJMoa1200690 CrossRefPubMedPubMedCentral

18.

Durgan K, Ali M, Warner P, Latchman YE (2011) Targeting NKT cells and PD-L1 pathway results in augmented anti-tumor responses in a melanoma model. Cancer Immunol Immunother 60:547–558. doi:10.1007/s00262-010-0963-5 CrossRefPubMedPubMedCentral

19.

Parekh VV, Lalani S, Kim S, Halder R, Azuma M, Yagita H, Kumar V, Wu L, Kaer LV (2009) PD-1/PD-L blockade prevents anergy induction and enhances the anti-tumor activities of glycolipid-activated invariant NKT cells. J Immunol 182:2816–2826. doi:10.4049/jimmunol.0803648 CrossRefPubMedPubMedCentral

20.

Chang WS, Kim YJ, Kim YS, Lee JM, Azuma M, Yagita H, Kang CY (2008) Cutting edge: programmed death-1/programmed death ligand 1 interaction regulates the induction and maintenance of invariant NKT cell anergy. J Immunol 181:6707–6710CrossRefPubMed

21.

Kee SJ, Kwon YS, Park YW et al (2012) Dysfunction of natural killer T cells in patients with active Mycobacterium tuberculosis infection. Infect Immun 80:2100–2108. doi:10.1128/IAI.06018-11 CrossRefPubMedPubMedCentral

22.

Singh A, Dey AB, Mohan A, Mitra DK (2014) Programmed death-1 receptor suppresses gamma-IFN producing NKT cells in human tuberculosis. Tuberculosis 94:197–206. doi:10.1016/j.tube.2014.01.005 CrossRefPubMed

23.

Moll M, Kuylenstierna C, Gonzalez VD, Andersson SK, Bosnjak L, Sonnerborg A, Quigley MF, Sandberg JK (2009) Severe functional impairment and elevated PD-1 expression in CD1d-restricted NKT cells retained during chronic HIV-1 infection. Eur J Immunol 39:902–911. doi:10.1002/eji.200838780 CrossRefPubMedPubMedCentral

24.

Carpenito C, Milone MC, Hassan R et al (2009) Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains. Proc Natl Acad Sci USA 106:3360–3365. doi:10.1073/pnas.0813101106 CrossRefPubMedPubMedCentral

25.

Sugamata R, Sugawara A, Nagao T et al (2014) Leucomycin A3, a 16-membered macrolide antibiotic, inhibits influenza A virus infection and disease progression. J Antibiot 67:213–222. doi:10.1038/ja.2013.132 CrossRefPubMed

26.

Ishikawa E, Motohashi S, Ishikawa A et al (2005) Dendritic cell maturation by CD11c- T cells and Vα24+ natural killer T-cell activation by α-galactosylceramide. Int J Cancer 117:265–273. doi:10.1002/ijc.21197 CrossRefPubMed

27.

Park JJ, Omiya R, Matsumura Y et al (2010) B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance. Blood 116:1291–1298. doi:10.1182/blood-2010-01-265975 CrossRefPubMedPubMedCentral

28.

Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12:252–264. doi:10.1038/nrc3239 CrossRefPubMedPubMedCentral

29.

Akbari O, Stock P, Singh AK, Lombardi V, Lee WL, Freeman GJ, Sharpe AH, Umetsu DT, Dekruyff RH (2010) PD-L1 and PD-L2 modulate airway inflammation and iNKT-cell-dependent airway hyperreactivity in opposing directions. Mucosal Immunol 3:81–91. doi:10.1038/mi.2009.112 CrossRefPubMed

30.

Dong H, Strome SE, Salomao DR et al (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8:793–800. doi:10.1038/nm730 CrossRefPubMed

31.

Parry RV, Chemnitz JM, Frauwirth KA, Lanfranco AR, Braunstein I, Kobayashi SV, Linsley PS, Thompson CB, Riley JL (2005) CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol 25:9543–9553. doi:10.1128/MCB.25.21.9543-9553.2005 CrossRefPubMedPubMedCentral

32.

Jiang K, Zong B, Gilvary DL, Corliss BC, Hong-Geller E, Wei S, Djeu JY (2000) Pivotal role of phosphoinositide-3 kinase in regulation of cytotoxicity in natural killer cells. Nat Immunol 1:419–425CrossRefPubMed

33.

Wang J, Cheng L, Wondimu Z, Swain M, Santamaria P, Yang Y (2009) Cutting edge: CD28 engagement releases antigen-activated invariant NKT cells from the inhibitory effects of PD-1. J Immunol 182:6644–6647. doi:10.4049/jimmunol.0804050 CrossRefPubMed

34.

Godfrey DI, Kronenberg M (2004) Going both ways: immune regulation via CD1d-dependent NKT cells. J Clin Invest 114:1379–1388. doi:10.1172/jci200423594 CrossRefPubMedPubMedCentral

35.

Mise N, Takami M, Suzuki A et al (2016) Antibody-dependent cellular cytotoxicity toward neuroblastoma enhanced by activated invariant natural killer T cells. Cancer Sci 107:233–241. doi:10.1111/cas.12882 CrossRefPubMedPubMedCentral

36.

Rozali EN, Hato SV, Robinson BW, Lake RA, Lesterhuis WJ (2012) Programmed death ligand 2 in cancer-induced immune suppression. Clin Dev Immunol 2012:656340. doi:10.1155/2012/656340 CrossRefPubMedPubMedCentral

37.

Kienzle N, Buttigieg K, Groves P, Kawula T, Kelso A (2002) A clonal culture system demonstrates that IL-4 induces a subpopulation of noncytolytic T cells with low CD8, perforin, and granzyme expression. J Immunol 168:1672–1681. doi:10.4049/jimmunol.168.4.1672 CrossRefPubMed

Title: Blockade of programmed death-1/programmed death ligand pathway enhances the antitumor immunity of human invariant natural killer T cells
Authors: Toshiko Kamata
Akane Suzuki
Naoko Mise
Fumie Ihara
Mariko Takami
Yuji Makita
Atsushi Horinaka
Kazuaki Harada
Naoki Kunii
Shigetoshi Yoshida
Ichiro Yoshino
Toshinori Nakayama
Shinichiro Motohashi
Publication date: 01-12-2016
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 12/2016
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-016-1901-y

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