Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy.
Journal
Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119
Informations de publication
Date de publication:
23 Nov 2023
23 Nov 2023
Historique:
received:
17
03
2023
accepted:
11
10
2023
medline:
24
11
2023
pubmed:
24
11
2023
entrez:
23
11
2023
Statut:
aheadofprint
Résumé
Dendritic cells (DCs) are antigen-presenting myeloid cells that regulate T cell activation, trafficking and function. Monocyte-derived DCs pulsed with tumor antigens have been tested extensively for therapeutic vaccination in cancer, with mixed clinical results. Here, we present a cell-therapy platform based on mouse or human DC progenitors (DCPs) engineered to produce two immunostimulatory cytokines, IL-12 and FLT3L. Cytokine-armed DCPs differentiated into conventional type-I DCs (cDC1) and suppressed tumor growth, including melanoma and autochthonous liver models, without the need for antigen loading or myeloablative host conditioning. Tumor response involved synergy between IL-12 and FLT3L and was associated with natural killer and T cell infiltration and activation, M1-like macrophage programming and ischemic tumor necrosis. Antitumor immunity was dependent on endogenous cDC1 expansion and interferon-γ signaling but did not require CD8
Identifiants
pubmed: 37996514
doi: 10.1038/s43018-023-00668-y
pii: 10.1038/s43018-023-00668-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : EVOLVE-725051
Informations de copyright
© 2023. The Author(s).
Références
Spranger, S., Dai, D., Horton, B. & Gajewski, T. F. Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy. Cancer Cell 31, 711–723.e4 (2017).
pubmed: 28486109
pmcid: 5650691
doi: 10.1016/j.ccell.2017.04.003
Zagorulya, M. & Spranger, S. Once upon a prime: DCs shape cancer immunity. Trends Cancer 9, 172–184 (2023).
pubmed: 36357313
doi: 10.1016/j.trecan.2022.10.006
Perez, C. R. & De Palma, M. Engineering dendritic cell vaccines to improve cancer immunotherapy. Nat. Commun. 10, 5408 (2019).
pubmed: 31776331
pmcid: 6881351
doi: 10.1038/s41467-019-13368-y
Cabeza-Cabrerizo, M., Cardoso, A., Minutti, C. M., Pereira da Costa, M. & Reis e Sousa, C. Dendritic cells revisited. Annu. Rev. Immunol. 39, 131–166 (2021).
pubmed: 33481643
doi: 10.1146/annurev-immunol-061020-053707
Gerhard, G. M., Bill, R., Messemaker, M., Klein, A. M. & Pittet, M. J. Tumor-infiltrating dendritic cell states are conserved across solid human cancers. J. Exp. Med. 218, e20200264 (2021).
pubmed: 33601412
doi: 10.1084/jem.20200264
Martinez-Usatorre, A. & De Palma, M. Dendritic cell cross-dressing and tumor immunity. EMBO Mol. Med. 14, e16523 (2022).
pubmed: 35959554
pmcid: 9549722
doi: 10.15252/emmm.202216523
Squadrito, M. L., Cianciaruso, C., Hansen, S. K. & De Palma, M. EVIR: chimeric receptors that enhance dendritic cell cross-dressing with tumor antigens. Nat. Methods 15, 183–186 (2018).
pubmed: 29355847
pmcid: 5833950
doi: 10.1038/nmeth.4579
Palucka, K. & Banchereau, J. Dendritic-cell-based therapeutic cancer vaccines. Immunity 39, 38–48 (2013).
pubmed: 23890062
pmcid: 3788678
doi: 10.1016/j.immuni.2013.07.004
Melief, C. J. M. Cancer immunotherapy by dendritic cells. Immunity 29, 372–383 (2008).
pubmed: 18799145
doi: 10.1016/j.immuni.2008.08.004
Harari, A., Graciotti, M., Bassani-Sternberg, M. & Kandalaft, L. E. Antitumour dendritic cell vaccination in a priming and boosting approach. Nat. Rev. Drug Discov. 19, 635–652 (2020).
pubmed: 32764681
doi: 10.1038/s41573-020-0074-8
Wculek, S. K. et al. Dendritic cells in cancer immunology and immunotherapy. Nat. Rev. Immunol. 20, 7–24 (2020).
pubmed: 31467405
doi: 10.1038/s41577-019-0210-z
Spranger, S. et al. Density of immunogenic antigens does not explain the presence or absence of the T-cell-inflamed tumor microenvironment in melanoma. Proc. Natl Acad. Sci. USA 113, E7759–E7768 (2016).
pubmed: 27837020
pmcid: 5137753
doi: 10.1073/pnas.1609376113
Scheper, W. et al. Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers. Nat. Med. 25, 89–94 (2019).
pubmed: 30510250
doi: 10.1038/s41591-018-0266-5
Mayer, C. T. et al. Selective and efficient generation of functional Batf3-dependent CD103
pubmed: 25100743
pmcid: 4260363
doi: 10.1182/blood-2013-12-545772
Helft, J. et al. GM-CSF mouse bone marrow cultures comprise a heterogeneous population of CD11c
pubmed: 26084029
doi: 10.1016/j.immuni.2015.05.018
Schraml, B. U. et al. Genetic tracing via DNGR-1 expression history defines dendritic cells as a hematopoietic lineage. Cell 154, 843–858 (2013).
pubmed: 23953115
doi: 10.1016/j.cell.2013.07.014
Edelson, B. T. et al. Peripheral CD103
pubmed: 20351058
pmcid: 2856032
doi: 10.1084/jem.20091627
Hammerich, L. et al. Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination. Nat. Med. 25, 814–824 (2019).
pubmed: 30962585
doi: 10.1038/s41591-019-0410-x
Salmon, H. et al. Expansion and activation of CD103
pubmed: 27096321
pmcid: 4980762
doi: 10.1016/j.immuni.2016.03.012
Zundler, S. & Neurath, M. F. Interleukin-12: functional activities and implications for disease. Cytokine Growth Factor Rev. 26, 559–568 (2015).
pubmed: 26182974
doi: 10.1016/j.cytogfr.2015.07.003
Bonini, C. et al. Safety of retroviral gene marking with a truncated NGF receptor. Nat. Med. 9, 367–369 (2003).
pubmed: 12669036
doi: 10.1038/nm0403-367
Wu, R. et al. SOX2 promotes resistance of melanoma with PD-L1 high expression to T-cell-mediated cytotoxicity that can be reversed by SAHA. J. Immunother. Cancer 8, e001037 (2020).
pubmed: 33158915
pmcid: 7651737
doi: 10.1136/jitc-2020-001037
Shi, G., Scott, M., Mangiamele, C. G. & Heller, R. Modification of the tumor microenvironment enhances anti-PD-1 immunotherapy in metastatic melanoma. Pharmaceutics 14, 2429 (2022).
pubmed: 36365247
pmcid: 9695203
doi: 10.3390/pharmaceutics14112429
Baer, C. et al. Suppression of microRNA activity amplifies IFN-γ-induced macrophage activation and promotes anti-tumour immunity. Nat. Cell Biol. 18, 790–802 (2016).
pubmed: 27295554
doi: 10.1038/ncb3371
Beltraminelli, T., Perez, C. R. & De Palma, M. Disentangling the complexity of tumor-derived extracellular vesicles. Cell Rep. 35, 108960 (2021).
pubmed: 33826890
doi: 10.1016/j.celrep.2021.108960
Crescitelli, R., Lässer, C. & Lötvall, J. Isolation and characterization of extracellular vesicle subpopulations from tissues. Nat. Protoc. 16, 1548–1580 (2021).
pubmed: 33495626
doi: 10.1038/s41596-020-00466-1
Kammertoens, T. et al. Tumour ischaemia by interferon-γ resembles physiological blood vessel regression. Nature 545, 98–102 (2017).
pubmed: 28445461
pmcid: 5567674
doi: 10.1038/nature22311
Yuan, F. et al. Time-dependent vascular regression and permeability changes in established human tumor xenografts induced by an anti-vascular endothelial growth factor/vascular permeability factor antibody. Proc. Natl Acad. Sci. USA 93, 14765–14770 (1996).
pubmed: 8962129
pmcid: 26210
doi: 10.1073/pnas.93.25.14765
Cianciaruso, C. et al. Molecular profiling and functional analysis of macrophage-derived tumor extracellular vesicles. Cell Rep. 27, 3062–3080.e11 (2019).
pubmed: 31167148
pmcid: 6581796
doi: 10.1016/j.celrep.2019.05.008
Mombaerts, P. et al. RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68, 869–877 (1992).
pubmed: 1547488
doi: 10.1016/0092-8674(92)90030-G
Percin, G. I. et al. CSF1R regulates the dendritic cell pool size in adult mice via embryo-derived tissue-resident macrophages. Nat. Commun. 9, 5279 (2018).
pubmed: 30538245
pmcid: 6290072
doi: 10.1038/s41467-018-07685-x
Köberle, B. & Schoch, S. Platinum complexes in colorectal cancer and other solid tumors. Cancers 13, 2073 (2021).
pubmed: 33922989
pmcid: 8123298
doi: 10.3390/cancers13092073
Molina-Sánchez, P. et al. Cooperation between distinct cancer driver genes underlies intertumor heterogeneity in hepatocellular carcinoma. Gastroenterology 159, 2203–2220.e14 (2020).
pubmed: 32814112
doi: 10.1053/j.gastro.2020.08.015
Ruiz de Galarreta, M. et al. β-Catenin activation promotes immune escape and resistance to anti-PD-1 therapy in hepatocellular carcinoma. Cancer Discov. 9, 1124–1141 (2019).
pubmed: 31186238
doi: 10.1158/2159-8290.CD-19-0074
Marofi, F. et al. CAR T cells in solid tumors: challenges and opportunities. Stem Cell Res. Ther. 12, 81 (2021).
pubmed: 33494834
pmcid: 7831265
doi: 10.1186/s13287-020-02128-1
Genoud, V. et al. Responsiveness to anti-PD-1 and anti-CTLA-4 immune checkpoint blockade in SB28 and GL261 mouse glioma models. Oncoimmunology 7, e1501137 (2018).
pubmed: 30524896
pmcid: 6279422
doi: 10.1080/2162402X.2018.1501137
Prapa, M. et al. GD2 CAR T cells against human glioblastoma. npj Precis. Oncol. 5, 93 (2021).
pubmed: 34707200
pmcid: 8551169
doi: 10.1038/s41698-021-00233-9
Majzner, R. G. et al. GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Nature 603, 934–941 (2022).
pubmed: 35130560
pmcid: 8967714
doi: 10.1038/s41586-022-04489-4
Fares, I. et al. Cord blood expansion. Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal. Science 345, 1509–1512 (2014).
pubmed: 25237102
pmcid: 4372335
doi: 10.1126/science.1256337
Breton, G., Lee, J., Liu, K. & Nussenzweig, M. C. Defining human dendritic cell progenitors by multiparametric flow cytometry. Nat. Protoc. 10, 1407–1422 (2015).
pubmed: 26292072
pmcid: 4607256
doi: 10.1038/nprot.2015.092
Gupta, A. O. & Wagner, J. E. Umbilical cord blood transplants: current status and evolving therapies. Front. Pediatr. 8, 570282 (2020).
pubmed: 33123504
pmcid: 7567024
doi: 10.3389/fped.2020.570282
Iancu, E. M. et al. Clonotype selection and composition of human CD8 T cells specific for persistent herpes viruses varies with differentiation but is stable over time. J. Immunol. 183, 319–331 (2009).
pubmed: 19542443
doi: 10.4049/jimmunol.0803647
Neubert, N. J. et al. T cell-induced CSF1 promotes melanoma resistance to PD1 blockade. Sci. Transl. Med. 10, eaan3311 (2018).
pubmed: 29643229
pmcid: 5957531
doi: 10.1126/scitranslmed.aan3311
Maraskovsky, E. et al. Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified. J. Exp. Med. 184, 1953–1962 (1996).
pubmed: 8920882
doi: 10.1084/jem.184.5.1953
Gocher, A. M., Workman, C. J. & Vignali, D. A. A. Interferon-γ: teammate or opponent in the tumour microenvironment? Nat. Rev. Immunol. 22, 158–172 (2022).
pubmed: 34155388
doi: 10.1038/s41577-021-00566-3
Ashour, D. et al. IL-12 from endogenous cDC1, and not vaccine DC, is required for Th1 induction. JCI Insight 5, e135143 (2020).
pubmed: 32434994
pmcid: 7259537
doi: 10.1172/jci.insight.135143
Broz, M. L. et al. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell 26, 638–652 (2014).
pubmed: 25446897
pmcid: 4254577
doi: 10.1016/j.ccell.2014.09.007
Gardner, A. et al. TIM-3 blockade enhances IL-12-dependent antitumor immunity by promoting CD8
pubmed: 34987021
pmcid: 8734033
doi: 10.1136/jitc-2021-003571
Martínez-López, M., Iborra, S., Conde-Garrosa, R. & Sancho, D. Batf3-dependent CD103
pubmed: 25312824
doi: 10.1002/eji.201444651
Ruffell, B. et al. Macrophage IL-10 blocks CD8
pubmed: 25446896
pmcid: 4254570
doi: 10.1016/j.ccell.2014.09.006
Pfirschke, C. et al. Macrophage-targeted therapy unlocks antitumoral cross-talk between IFNγ-secreting lymphocytes and IL12-producing dendritic cells. Cancer Immunol. Res. 10, 40–55 (2022).
pubmed: 34795032
doi: 10.1158/2326-6066.CIR-21-0326
Curran, M. A. & Allison, J. P. Tumor vaccines expressing Flt3 ligand synergize with CTLA-4 blockade to reject preimplanted tumors. Cancer Res. 69, 7747–7755 (2009).
pubmed: 19738077
pmcid: 2756314
doi: 10.1158/0008-5472.CAN-08-3289
Hegde, S. et al. Dendritic cell paucity leads to dysfunctional immune surveillance in pancreatic cancer. Cancer Cell 37, 289–307.e9 (2020).
pubmed: 32183949
pmcid: 7181337
doi: 10.1016/j.ccell.2020.02.008
Bödder, J. et al. Harnessing the cDC1-NK cross-talk in the tumor microenvironment to battle cancer. Front. Immunol. 11, 631713 (2020).
pubmed: 33679726
doi: 10.3389/fimmu.2020.631713
Rottinghaus, E. K., Vesosky, B. & Turner, J. Interleukin-12 is sufficient to promote antigen-independent interferon-γ production by CD8 T cells in old mice. Immunology 128, e679–e690 (2009).
pubmed: 19740329
pmcid: 2753923
doi: 10.1111/j.1365-2567.2009.03061.x
de Vries, N. L. et al. γδ T cells are effectors of immunotherapy in cancers with HLA class I defects. Nature 613, 743–750 (2023).
pubmed: 36631610
pmcid: 9876799
doi: 10.1038/s41586-022-05593-1
Hsu, J. et al. Contribution of NK cells to immunotherapy mediated by PD-1/PD-L1 blockade. J. Clin. Invest. 128, 4654–4668 (2018).
pubmed: 30198904
pmcid: 6159991
doi: 10.1172/JCI99317
Larson, R. C. et al. CAR T cell killing requires the IFNγR pathway in solid but not liquid tumours. Nature 604, 563–570 (2022).
pubmed: 35418687
doi: 10.1038/s41586-022-04585-5
Boulch, M. et al. Tumor-intrinsic sensitivity to the pro-apoptotic effects of IFN-γ is a major determinant of CD4
pubmed: 37248395
pmcid: 10368531
doi: 10.1038/s43018-023-00570-7
Walsh, M. J. et al. IFNγ is a central node of cancer immune equilibrium. Cell Rep. 42, 112219 (2023).
pubmed: 36881506
pmcid: 10214249
doi: 10.1016/j.celrep.2023.112219
Kruse, B. et al. CD4
pubmed: 37316667
pmcid: 10307640
doi: 10.1038/s41586-023-06199-x
Gungabeesoon, J. et al. A neutrophil response linked to tumor control in immunotherapy. Cell 186, 1448–1464.e20 (2023).
pubmed: 37001504
doi: 10.1016/j.cell.2023.02.032
Aqbi, H. F., Wallace, M., Sappal, S., Payne, K. K. & Manjili, M. H. IFN-γ orchestrates tumor elimination, tumor dormancy, tumor escape, and progression. J. Leukoc. Biol. 103, 1219–1223 (2018).
doi: 10.1002/JLB.5MIR0917-351R
Benci, J. L. et al. Opposing functions of interferon coordinate adaptive and innate immune responses to cancer immune checkpoint blockade. Cell 178, 933–948.e14 (2019).
pubmed: 31398344
pmcid: 6830508
doi: 10.1016/j.cell.2019.07.019
De Palma, M. et al. Tumor-targeted interferon-α delivery by Tie2-expressing monocytes inhibits tumor growth and metastasis. Cancer Cell 14, 299–311 (2008).
pubmed: 18835032
doi: 10.1016/j.ccr.2008.09.004
Escobar, G. et al. Genetic engineering of hematopoiesis for targeted IFN-α delivery inhibits breast cancer progression. Sci. Transl. Med. 6, 217ra3 (2014).
pubmed: 24382895
doi: 10.1126/scitranslmed.3006353
Birocchi, F. et al. Targeted inducible delivery of immunoactivating cytokines reprograms glioblastoma microenvironment and inhibits growth in mouse models. Sci. Transl. Med. 14, eabl4106 (2022).
pubmed: 35857642
doi: 10.1126/scitranslmed.abl4106
Kaczanowska, S. et al. Genetically engineered myeloid cells rebalance the core immune suppression program in metastasis. Cell 184, 2033–2052.e21 (2021).
pubmed: 33765443
pmcid: 8344805
doi: 10.1016/j.cell.2021.02.048
Rossari, F., Birocchi, F., Naldini, L. & Coltella, N. Gene-based delivery of immune-activating cytokines for cancer treatment. Trends Mol. Med. 29, 329–342 (2023).
pubmed: 36828711
doi: 10.1016/j.molmed.2023.01.006
Szymczak-Workman, A. L., Vignali, K. M. & Vignali, D. A. A. Design and construction of 2A peptide-linked multicistronic vectors. Cold Spring Harb. Protoc. 2012, 199–204 (2012).
pubmed: 22301656
doi: 10.1101/pdb.ip067876
Lode, H. N. et al. Gene therapy with a single chain interleukin 12 fusion protein induces T cell-dependent protective immunity in a syngeneic model of murine neuroblastoma. Proc. Natl Acad. Sci. USA 95, 2475–2480 (1998).
pubmed: 9482910
pmcid: 19380
doi: 10.1073/pnas.95.5.2475
De Palma, M., Venneri, M. A., Roca, C. & Naldini, L. Targeting exogenous genes to tumor angiogenesis by transplantation of genetically modified hematopoietic stem cells. Nat. Med. 9, 789–795 (2003).
pubmed: 12740570
doi: 10.1038/nm871
De Palma, M. & Naldini, L. Transduction of a gene expression cassette using advanced generation lentiviral vectors. Methods Enzymol. 346, 514–529 (2002).
pubmed: 11883088
doi: 10.1016/S0076-6879(02)46074-0
Ran, F. A. et al. Genome engineering using the CRISPR–Cas9 system. Nat. Protoc. 8, 2281–2308 (2013).
pubmed: 24157548
pmcid: 3969860
doi: 10.1038/nprot.2013.143
Yuan, D. et al. Kupffer cell-derived Tnf triggers cholangiocellular tumorigenesis through JNK due to chronic mitochondrial dysfunction and ROS. Cancer Cell 31, 771–789.e6 (2017).
pubmed: 28609656
pmcid: 7909318
doi: 10.1016/j.ccell.2017.05.006
Tschaharganeh, D. F. et al. p53-dependent Nestin regulation links tumor suppression to cellular plasticity in liver cancer. Cell 158, 579–592 (2014).
pubmed: 25083869
pmcid: 4221237
doi: 10.1016/j.cell.2014.05.051
Genolet, R. et al. TCR sequencing and cloning methods for repertoire analysis and isolation of tumor-reactive TCRs. Cell Rep. Methods 3, 100459 (2023).
pubmed: 37159666
pmcid: 10163020
doi: 10.1016/j.crmeth.2023.100459