Anticancer effects of chemokine-directed antigen delivery to a cross-presenting dendritic cell subset with immune checkpoint blockade
| Autor: | Keiji Hayata, Mikihito Nakamori, Tomokazu Ohta, Yuji Kitahata, Masahiro Katsuda, Hiroki Yamaue, Hiroaki Hemmi, Izumi Sasaki, Masaki Nakamura, Atsushi Miyamoto, Kenji Matsuda, Takashi Orimo, Soichiro Okura, Toshiyasu Ojima, Yuri Fukuda-Ohta, Yuki Mizumoto, Koji Tamada, Masanaka Sugiyama, Motoki Miyazawa, Tsuneyasu Kaisho |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Chemokine Cancer immunotherapy Immunopotentiator CD8-Positive T-Lymphocytes Cancer Vaccines Article 03 medical and health sciences 0302 clinical medicine Cross-Priming Cell Line Tumor MHC class I Animals Antigens Immune Checkpoint Inhibitors 030304 developmental biology 0303 health sciences biology Chemistry Dendritic cell Dendritic Cells Neoplasms Experimental Fusion protein Immune checkpoint Chemokines C Mice Inbred C57BL Poly I-C Oncology 030220 oncology & carcinogenesis Vaccines Subunit biology.protein Cancer research Immunization CD8 XCL1 |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | BackgroundCancer peptide vaccines show only marginal effects against cancers. Immune checkpoint inhibitors (ICIs) show significant curative effects in certain types of cancers, but the response rate is still limited. In this study, we aim to improve cancer peptide vaccination by targeting Ag peptides selectively to a dendritic cell (DC) subset, XCR1-expressing DCs (XCR1+DCs), with high ability to support CD8+T-cell responses.MethodsWe have generated a fusion protein, consisting of an Ag peptide presented with MHC class I, and an XCR1 ligand, XCL1, and examined its effects on antitumour immunity in mice.ResultsThe fusion protein was delivered to XCR1+DCs in an XCR1-dependent manner. Immunisation with the fusion protein plus an immune adjuvant, polyinosinic:polycytidylic acids (poly(I:C)), more potently induced Ag-specific CD8+T-cell responses through XCR1 than the Ag peptide plus poly(I:C) or the Ag protein plus poly(I:C). The fusion protein plus poly(I:C) inhibited the tumour growth efficiently in the prophylactic and therapeutic tumour models. Furthermore, the fusion protein plus poly(I:C) showed suppressive effects on tumour growth in synergy with anti-PD-1 Ab.ConclusionsCancer Ag targeting to XCR1+DCs should be a promising procedure as a combination anticancer therapy with immune checkpoint blockade. |
| Databáze: | OpenAIRE |
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