A dietary commensal microbe enhances antitumor immunity by activating tumor macrophages to sequester iron.
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
25 Apr 2024
25 Apr 2024
Historique:
received:
21
12
2023
accepted:
13
03
2024
medline:
26
4
2024
pubmed:
26
4
2024
entrez:
25
4
2024
Statut:
aheadofprint
Résumé
Innate immune cells generate a multifaceted antitumor immune response, including the conservation of essential nutrients such as iron. These cells can be modulated by commensal bacteria; however, identifying and understanding how this occurs is a challenge. Here we show that the food commensal Lactiplantibacillus plantarum IMB19 augments antitumor immunity in syngeneic and xenograft mouse tumor models. Its capsular heteropolysaccharide is the major effector molecule, functioning as a ligand for TLR2. In a two-pronged manner, it skews tumor-associated macrophages to a classically active phenotype, leading to generation of a sustained CD8
Identifiants
pubmed: 38664585
doi: 10.1038/s41590-024-01816-x
pii: 10.1038/s41590-024-01816-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.
Références
Demaria, O. et al. Harnessing innate immunity in cancer therapy. Nature 574, 45–56 (2019).
pubmed: 31578484
doi: 10.1038/s41586-019-1593-5
Gajewski, T. F., Schreiber, H. & Fu, Y. X. Innate and adaptive immune cells in the tumor microenvironment. Nat. Immunol. 14, 1014–1022 (2013).
pubmed: 24048123
pmcid: 4118725
doi: 10.1038/ni.2703
Ganz, T. & Nemeth, E. Iron homeostasis in host defence and inflammation. Nat. Rev. Immunol. 15, 500–510 (2015).
pubmed: 26160612
pmcid: 4801113
doi: 10.1038/nri3863
Belkaid, Y. & Hand, T. W. Role of the microbiota in immunity and inflammation. Cell 157, 121–141 (2014).
pubmed: 24679531
pmcid: 4056765
doi: 10.1016/j.cell.2014.03.011
Vetizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015).
pubmed: 26541610
pmcid: 4721659
doi: 10.1126/science.aad1329
Sivan, A. et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350, 1084–1089 (2015).
pubmed: 26541606
pmcid: 4873287
doi: 10.1126/science.aac4255
Giunta, E. F. et al. Baseline IFN-γ and IL-10 expression in PBMCs could predict response to PD-1 checkpoint inhibitors in advanced melanoma patients. Sci. Rep. 10, 17626 (2020).
pubmed: 33077770
pmcid: 7573589
doi: 10.1038/s41598-020-72711-2
Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature 486, 222–227 (2012).
pubmed: 22699611
pmcid: 3376388
doi: 10.1038/nature11053
Li, K. et al. CD8(+) T cell immunity blocks the metastasis of carcinogen-exposed breast cancer. Sci. Adv. 7, eabd8936 (2021).
pubmed: 34144976
pmcid: 8213232
doi: 10.1126/sciadv.abd8936
Watowich, M. B., Gilbert, M. R. & Larion, M. T cell exhaustion in malignant gliomas. Trends Cancer 9, 270–292 (2023).
pubmed: 36681605
pmcid: 10038906
doi: 10.1016/j.trecan.2022.12.008
Douglas, G. M. et al. PICRUSt2 for prediction of metagenome functions. Nat. Biotechnol. 38, 685–688 (2020).
pubmed: 32483366
pmcid: 7365738
doi: 10.1038/s41587-020-0548-6
Remus, D. M. et al. Impact of 4 Lactobacillus plantarum capsular polysaccharide clusters on surface glycan composition and host cell signaling. Micro. Cell Fact. 11, 149 (2012).
doi: 10.1186/1475-2859-11-149
Garcia-Vello, P. et al. Structural features and immunological perception of the cell surface glycans of Lactobacillus plantarum: a novel rhamnose-rich polysaccharide and teichoic acids. Carbohydr. Polym. 233, 115857 (2020).
pubmed: 32059908
doi: 10.1016/j.carbpol.2020.115857
Tietze, J. K. et al. The proportion of circulating CD45RO(+)CD8(+) memory T cells is correlated with clinical response in melanoma patients treated with ipilimumab. Eur. J. Cancer 75, 268–279 (2017).
pubmed: 28242504
doi: 10.1016/j.ejca.2016.12.031
Zhao, X., Shan, Q. & Xue, H. H. TCF1 in T cell immunity: a broadened frontier. Nat. Rev. Immunol. https://doi.org/10.1038/s41577-021-00563-6 (2021).
doi: 10.1038/s41577-021-00563-6
pubmed: 34127847
Roh, W. et al. Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance. Sci. Transl. Med. 9, eaah3560 (2017).
pubmed: 28251903
pmcid: 5819607
doi: 10.1126/scitranslmed.aah3560
Rudqvist, N. P. et al. Radiotherapy and CTLA-4 blockade shape the TCR repertoire of tumor-infiltrating T cells. Cancer Immunol. Res. 6, 139–150 (2018).
pubmed: 29180535
doi: 10.1158/2326-6066.CIR-17-0134
Huang, C. P., Liu, L. X. & Shyr, C. R. Tumor-associated macrophages facilitate bladder cancer progression by increasing cell growth, migration, invasion and cytokine expression. Anticancer Res. 40, 2715–2724 (2020).
pubmed: 32366417
doi: 10.21873/anticanres.14243
Yost, K. E. et al. Clonal replacement of tumor-specific T cells following PD-1 blockade. Nat. Med. 25, 1251–1259 (2019).
pubmed: 31359002
pmcid: 6689255
doi: 10.1038/s41591-019-0522-3
Muntjewerff, E. M., Meesters, L. D. & van den Bogaart, G. Antigen cross-presentation by macrophages. Front. Immunol. 11, 1276 (2020).
pubmed: 32733446
pmcid: 7360722
doi: 10.3389/fimmu.2020.01276
Bain, C. C. et al. Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nat. Immunol. 15, 929–937 (2014).
pubmed: 25151491
pmcid: 4169290
doi: 10.1038/ni.2967
Tamoutounour, S. et al. CD64 distinguishes macrophages from dendritic cells in the gut and reveals the Th1-inducing role of mesenteric lymph node macrophages during colitis. Eur. J. Immunol. 42, 3150–3166 (2012).
pubmed: 22936024
doi: 10.1002/eji.201242847
Weber, B., Saurer, L., Schenk, M., Dickgreber, N. & Mueller, C. CX3CR1 defines functionally distinct intestinal mononuclear phagocyte subsets which maintain their respective functions during homeostatic and inflammatory conditions. Eur. J. Immunol. 41, 773–779 (2011).
pubmed: 21341263
doi: 10.1002/eji.201040965
Buscher, K. et al. Natural variation of macrophage activation as disease-relevant phenotype predictive of inflammation and cancer survival. Nat. Commun. 8, 16041 (2017).
pubmed: 28737175
pmcid: 5527282
doi: 10.1038/ncomms16041
Muckenthaler, M. U., Rivella, S., Hentze, M. W. & Galy, B. A red carpet for iron metabolism. Cell 168, 344–361 (2017).
pubmed: 28129536
pmcid: 5706455
doi: 10.1016/j.cell.2016.12.034
Kroner, A. et al. TNF and increased intracellular iron alter macrophage polarization to a detrimental M1 phenotype in the injured spinal cord. Neuron 83, 1098–1116 (2014).
pubmed: 25132469
doi: 10.1016/j.neuron.2014.07.027
Pereira, M. et al. Acute iron deprivation reprograms human macrophage metabolism and reduces inflammation in vivo. Cell Rep. 28, 498–511 (2019).
pubmed: 31291584
pmcid: 6635384
doi: 10.1016/j.celrep.2019.06.039
Tannahill, G. M. et al. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature 496, 238–242 (2013).
pubmed: 23535595
pmcid: 4031686
doi: 10.1038/nature11986
Peyssonnaux, C. et al. HIF-1α expression regulates the bactericidal capacity of phagocytes. J. Clin. Invest. 115, 1806–1815 (2005).
pubmed: 16007254
pmcid: 1159132
doi: 10.1172/JCI23865
Winn, N. C., Volk, K. M. & Hasty, A. H. Regulation of tissue iron homeostasis: the macrophage ‘ferrostat’. JCI Insight 5, e132964 (2020).
pubmed: 31996481
pmcid: 7098718
doi: 10.1172/jci.insight.132964
Abreu, R., Quinn, F. & Giri, P. K. Role of the hepcidin-ferroportin axis in pathogen-mediated intracellular iron sequestration in human phagocytic cells. Blood Adv. 2, 1089–1100 (2018).
pubmed: 29764842
pmcid: 5965048
doi: 10.1182/bloodadvances.2017015255
Ganz, T. Iron in innate immunity: starve the invaders. Curr. Opin. Immunol. 21, 63–67 (2009).
pubmed: 19231148
pmcid: 2668730
doi: 10.1016/j.coi.2009.01.011
Cassat, J. E. & Skaar, E. P. Iron in infection and immunity. Cell Host Microbe 13, 509–519 (2013).
pubmed: 23684303
pmcid: 3676888
doi: 10.1016/j.chom.2013.04.010
Gozzelino, R., Jeney, V. & Soares, M. P. Mechanisms of cell protection by heme oxygenase-1. Annu. Rev. Pharmacol. Toxicol. 50, 323–354 (2010).
pubmed: 20055707
doi: 10.1146/annurev.pharmtox.010909.105600
Chi, Y. et al. Cancer cells deploy lipocalin-2 to collect limiting iron in leptomeningeal metastasis. Science 369, 276–282 (2020).
pubmed: 32675368
pmcid: 7816199
doi: 10.1126/science.aaz2193
Mertens, C. et al. Intracellular iron chelation modulates the macrophage iron phenotype with consequences on tumor progression. PLoS ONE 11, e0166164 (2016).
pubmed: 27806101
pmcid: 5091876
doi: 10.1371/journal.pone.0166164
Lymboussaki, A. et al. The role of the iron responsive element in the control of ferroportin1/IREG1/MTP1 gene expression. J. Hepatol. 39, 710–715 (2003).
pubmed: 14568251
doi: 10.1016/S0168-8278(03)00408-2
Zhang, Z. et al. Ferroportin1 deficiency in mouse macrophages impairs iron homeostasis and inflammatory responses. Blood 118, 1912–1922 (2011).
pubmed: 21705499
doi: 10.1182/blood-2011-01-330324
Kotlov, N. et al. Clinical and biological subtypes of B-cell lymphoma revealed by microenvironmental signatures. Cancer Discov. 11, 1468–1489 (2021).
pubmed: 33541860
pmcid: 8178179
doi: 10.1158/2159-8290.CD-20-0839
Litchfield, K. et al. Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition. Cell 184, 596–614 (2021).
pubmed: 33508232
pmcid: 7933824
doi: 10.1016/j.cell.2021.01.002
Lenis, A. T., Lec, P. M., Chamie, K. & Mshs, M. D. Bladder cancer: a review. JAMA 324, 1980–1991 (2020).
pubmed: 33201207
doi: 10.1001/jama.2020.17598
Balar, A. V. et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet 389, 67–76 (2017).
pubmed: 27939400
doi: 10.1016/S0140-6736(16)32455-2
Cristescu, R. et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science 362, eaar3593 (2018).
pubmed: 30309915
pmcid: 6718162
doi: 10.1126/science.aar3593
Tanoue, T. et al. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature 565, 600–605 (2019).
pubmed: 30675064
doi: 10.1038/s41586-019-0878-z
Gonçalves, R. & Mosser, D. M. The isolation and characterization of murine macrophages. Curr. Protoc. Immunol. 111, 14.11.11–14.11.16 (2015).
doi: 10.1002/0471142735.im1401s111
Zhang, X., Goncalves, R. & Mosser, D. M. The isolation and characterization of murine macrophages. Curr. Protoc. Immunol. https://doi.org/10.1002/0471142735.im1401s83 (2008).
Lee, I., Ouk Kim, Y., Park, S. C. & Chun, J. OrthoANI: an improved algorithm and software for calculating average nucleotide identity. Int. J. Syst. Evol. Microbiol 66, 1100–1103 (2016).
pubmed: 26585518
doi: 10.1099/ijsem.0.000760
Bertsche, U. & Gust, A. A. Peptidoglycan isolation and binding studies with LysM-type pattern recognition receptors. Methods Mol. Biol. 1578, 1–12 (2017).
pubmed: 28220411
doi: 10.1007/978-1-4939-6859-6_1
Perez-Miranda, S., Cabirol, N., George-Tellez, R., Zamudio-Rivera, L. S. & Fernandez, F. J. O-CAS, a fast and universal method for siderophore detection. J. Microbiol. Methods 70, 127–131 (2007).
pubmed: 17507108
doi: 10.1016/j.mimet.2007.03.023
Kim, E. et al. Creation of bladder assembloids mimicking tissue regeneration and cancer. Nature 588, 664–669 (2020).
pubmed: 33328632
doi: 10.1038/s41586-020-3034-x
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
pubmed: 23104886
doi: 10.1093/bioinformatics/bts635
Lun, A. T. L. et al. EmptyDrops: distinguishing cells from empty droplets in droplet-based single-cell RNA sequencing data. Genome Biol. 20, 63 (2019).
pubmed: 30902100
pmcid: 6431044
doi: 10.1186/s13059-019-1662-y
McCarthy, D. J., Campbell, K. R., Lun, A. T. & Wills, Q. F. Scater: pre-processing, quality control, normalization and visualization of single-cell RNA-seq data in R. Bioinformatics 33, 1179–1186 (2017).
pubmed: 28088763
pmcid: 5408845
doi: 10.1093/bioinformatics/btw777
Lun, A. T., Bach, K. & Marioni, J. C. Pooling across cells to normalize single-cell RNA sequencing data with many zero counts. Genome Biol. 17, 75 (2016).
pubmed: 27122128
doi: 10.1186/s13059-016-0947-7
Satija, R., Farrell, J. A., Gennert, D., Schier, A. F. & Regev, A. Spatial reconstruction of single-cell gene expression data. Nat. Biotechnol. 33, 495–502 (2015).
pubmed: 25867923
pmcid: 4430369
doi: 10.1038/nbt.3192
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
pubmed: 25516281
pmcid: 4302049
doi: 10.1186/s13059-014-0550-8
Setty, M. et al. Characterization of cell fate probabilities in single-cell data with Palantir. Nat. Biotechnol. 37, 451–460 (2019).
pubmed: 30899105
pmcid: 7549125
doi: 10.1038/s41587-019-0068-4
Korsunsky, I. et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods 16, 1289–1296 (2019).
pubmed: 31740819
pmcid: 6884693
doi: 10.1038/s41592-019-0619-0
Ashburner, M. et al. Gene Ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat. Genet. 25, 25–29 (2000).
pubmed: 10802651
pmcid: 3037419
doi: 10.1038/75556
Gene Ontology Consortium. The Gene Ontology resource: enriching a GOld mine. Nucleic Acids Res. 49, D325–D334 (2021).
doi: 10.1093/nar/gkaa1113
Liberzon, A. et al. Molecular signatures database (MSigDB) 3.0. Bioinformatics 27, 1739–1740 (2011).
pubmed: 21546393
pmcid: 3106198
doi: 10.1093/bioinformatics/btr260
Colaprico, A. et al. TCGAbiolinks: an R/Bioconductor package for integrative analysis of TCGA data. Nucleic Acids Res. 44, e71 (2016).
pubmed: 26704973
doi: 10.1093/nar/gkv1507
Robinson, M. D. & Oshlack, A. A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol. 11, R25 (2010).
pubmed: 20196867
pmcid: 2864565
doi: 10.1186/gb-2010-11-3-r25
Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140 (2010).
pubmed: 19910308
doi: 10.1093/bioinformatics/btp616
Thorsson, V. et al. The immune landscape of cancer. Immunity 48, 812–830 (2018).
pubmed: 29628290
pmcid: 5982584
doi: 10.1016/j.immuni.2018.03.023
Howe, K. L. et al. Ensembl 2021. Nucleic Acids Res. 49, D884–D891 (2021).
pubmed: 33137190
doi: 10.1093/nar/gkaa942
Vilella, A. J. et al. EnsemblCompara GeneTrees: complete, duplication-aware phylogenetic trees in vertebrates. Genome Res. 19, 327–335 (2009).
pubmed: 19029536
pmcid: 2652215
doi: 10.1101/gr.073585.107
Lin, R. S. et al. Rejoinder to letter to the editor ‘the hazards of period specific and weighted hazard ratios’. Stat. Biopharm. Res. 12, 520–521 (2020).
pubmed: 34191985
pmcid: 8011488
doi: 10.1080/19466315.2020.1825522
Kim, M. J. et al. Deletion of PD-1 destabilizes the lineage identity and metabolic fitness of tumor-infiltrating regulatory T cells. Nat. Immunol. 24, 148–161 (2023).
pubmed: 36577929
doi: 10.1038/s41590-022-01373-1
Wertheimer, T. et al. IL-23 stabilizes an effector T(reg) cell program in the tumor microenvironment. Nat. Immunol. 25, 512–524 (2024).
pubmed: 38356059
pmcid: 10907296
doi: 10.1038/s41590-024-01755-7
Lee, J. CB-postech/NATURE-IMMUNOLOGY-TUMOR-MICROBIOME: 2024-03-28 Data analysis source codes - published version. Zenodo https://zenodo.org/doi/10.5281/zenodo.10888857 (2024).