Immunity, Journal Year: 2021, Volume and Issue: 54(12), P. 2825 - 2841.e10
Published: Dec. 1, 2021
Language: Английский
Immunity, Journal Year: 2021, Volume and Issue: 54(8), P. 1883 - 1900.e5
Published: July 30, 2021
Language: Английский
Citations
415
Trends in Immunology, Journal Year: 2022, Volume and Issue: 43(7), P. 546 - 563
Published: June 9, 2022
TAMs have diverse functions in cancer, reflecting the heterogenous nature of these immune cells. Here, we propose a new nomenclature to identify TAM subsets.Recent single cell multi-omics technologies, which allow clustering subsets an unbiased manner, significantly advanced our understanding molecular diversity mice and humans.Novel mechanisms potential therapeutic targets been identified that might regulate tumor-promoting function different subsets.TAM opens promising opportunities for envisaging putative cancer treatments. Tumor-associated macrophages (TAMs) multiple potent and, thus, represent important targets. These highlight TAMs. Recent omics technologies However, unifying annotation their signatures is lacking. review recent major studies transcriptome, epigenome, metabolome, spatial with specific focus on We also consensus model present avenues future research. one most abundant types tumors [1.Cassetta L. Pollard J.W. Targeting macrophages: approaches cancer.Nat. Rev. Drug Discov. 2018; 17: 887-904Crossref PubMed Scopus (650) Google Scholar]. Since initial decade ago [2.Qian B.Z. Macrophage enhances tumor progression metastasis.Cell. 2010; 141: 39-51Abstract Full Text PDF (3151) Scholar], functional now widely appreciated, many seminal field [3.Yang M. et al.Diverse microenvironments.Cancer Res. 78: 5492-5503Crossref (202) Scholar, 4.DeNardo D.G. Ruffell B. Macrophages as regulators tumour immunity immunotherapy.Nat. Immunol. 2019; 19: 369-382Crossref (643) 5.Lopez-Yrigoyen al.Macrophage targeting cancer.Ann. N. Y. Acad. Sci. 2021; 1499: 18-41Crossref (25) This array includes promotion growth, lineage plasticity, invasion, remodeling extracellular matrix, crosstalk endothelial, mesenchymal stromal cells, other cells; effects can result progression, metastasis (see Glossary), therapy resistance [6.Mantovani A. al.Tumour-associated treatment oncology.Nat. Clin. Oncol. 2017; 14: 399-416Crossref (1675) Scholar,7.Guc E. Redefining macrophage neutrophil biology metastatic cascade.Immunity. 54: 885-902Abstract (13) With wide application years seen explosion data illustrating cellular heterogeneity resulting unprecedented amount information TAMs, regardless main studies. Links between are emerging. terminology lacking, making direct comparisons full utilization sets difficult. In this review, summarize human data; include traditional nomenclatures, at levels single-cell transcriptomic, epigenomic, metabolic multi-omics, opportunities, directions. subsets. hope will serve starting point help build complete picture dynamic interactions tumor, well microenvironment (TME). A used describe has now-obsolete M1/M2 model, proposed ~20 ago; it separated into two distinct arms: M1 or 'classically' activated; M2 'alternatively' activated, largely based vitro stimulating type 1 2 cytokines [8.Mills C.D. al.M-1/M-2 Th1/Th2 paradigm.J. 2000; 164: 6166-6173Crossref The newer term 'M1-like' phenotype typically described proinflammatory induced by Toll-like receptor (TLR) ligands cytokines, namely IFN-γ TNF-α. Conversely, 'M2-like' having anti-inflammatory characteristics, being activated interleukin (IL)-4 IL-13, producing TGF-β profibrotic factors. nomenclature, albeit used, remains oversimplified [9.Martinez F.O. Gordon S. paradigm activation: time reassessment.F1000Prime Rep. 2014; 6: 13Crossref (2673) Scholar,10.Nahrendorf Swirski F.K. Abandoning network function.Circ. 2016; 119: 414-417Crossref (195) Indeed, significant morphology, function, surface marker expression observed resident-tissue (RTMs) from organs [11.Bleriot C. al.Determinants resident tissue identity function.Immunity. 2020; 52: 957-970Abstract (94) Scholar]; moreover, co-expression both gene almost all [12.Mulder K. al.Cross-tissue landscape monocytes health disease.Immunity. 1883-1900Abstract Therefore, spectrum polarization relates represents more sensible approach describing [10.Nahrendorf Scholar,13.Mosser D.M. Edwards J.P. Exploring activation.Nat. 2008; 8: 958-969Crossref (5864) normal homeostasis, tightly regulated niche-like local environment, recently [14.Guilliams al.Establishment maintenance niche.Immunity. 434-451Abstract (138) Another layer derives origin. Using lineage-tracing mice, illustrated mouse RTMs derived early erythromyeloid progenitors formed either yolk sac fetal liver [15.Geissmann F. al.Blood consist principal migratory properties.Immunity. 2003; 71-82Abstract (2514) Scholar,16.Gomez Perdiguero al.Tissue-resident originate yolk-sac-derived erythro-myeloid progenitors.Nature. 2015; 518: 547-551Crossref (1236) Additionally, adult may derive circulating monocytic precursors (monocytes) bone marrow [17.Cox al.Origins, biology, diseases macrophages.Annu. 39: 313-344Crossref (1) monocyte contribution varies among organs. For example, steady state, microglia central nervous system (CNS) solely [18.Hoeffel G. al.C-Myb(+) progenitor-derived give rise tissue-resident macrophages.Immunity. 42: 665-678Abstract (611) while dermal embryonic origin [19.Kolter J. al.A subset skin contributes surveillance regeneration nerves.Immunity. 50: 1482-1497Abstract (69) appreciated repeatedly reviewed [20.Pathria P. al.Targeting tumor-associated cancer.Trends 40: 310-327Abstract (382) Scholar,21.Guerriero J.L. Macrophages: road less traveled, changing anticancer therapy.Trends Mol. Med. 24: 472-489Abstract (143) Similar counterparts not only its ontogeny, but cues, including type, organ, subanatomic Identifying basis over past [5.Lopez-Yrigoyen advancements unveiling multidimensional complexity manner. research, oncology eventually fully understand cells hopefully use improve precision diagnosis therapy. Single RNA sequencing (scRNA-seq) technology revolutionized providing in-depth transcriptome level [22.Giladi al.Single-cell characterization haematopoietic trajectories homeostasis perturbed haematopoiesis.Nat. Cell Biol. 20: 836-846Crossref (139) substantial advances available experimental techniques bioinformatics pipelines years, scRNA-seq investigate [23.Lawson D.A. al.Tumour resolution.Nat. 1349-1360Crossref (230) Scholar,24.Ren X. al.Insights gained analysis microenvironment.Annu. 583-609Crossref (15) transcriptomic remain Two large-scale pan-cancer provided valuable regarding diversity. One study analyzed myeloid 380 samples across 15 210 patients through combination newly collected eight published [25.Cheng transcriptional atlas infiltrating cells.Cell. 184: 792-809Abstract (111) Comparison consistent presence CD14+ CD16+ tumor-infiltrating (TIMs), LYVE1+ interstitial non-cancer tissues, seven clusters: INHBA+ C1QC+ ISG15+ LNRP3+ SPP1+ compiled mononuclear phagocytes (MNPs) isolated 41 13 types, six common universe, termed MNP-VERSE. Monocyte clusters were then extracted reintegrated generate MoMac-VERSEi. regulatory inference (SCENIC) [26.Aibar al.SCENIC: clustering.Nat. Methods. 1083-1086Crossref (1003) authors classical monocytes, nonclassical five (HES1 TAM, C1Qhi TREM2 IL4I1 proliferating TAMs) Although nomenclatures studies, others, pattern transcriptomics By reviewing journals, found preserved (Table 1). Based signature genes, enriched pathways, predicated naming interferon-primed (IFN-TAMs), (Reg-TAMs), inflammatory cytokine-enriched (Inflam-TAMs), lipid-associated (LA-TAMs), pro-angiogenic (Angio-TAMs), RTM-like (RTM-TAMs), (Prolif-TAMs) Figure 1, Key figure). Furthermore, three TIMs Box 1).Table 1Mouse various TMEsaBlack font: genes clusters; blue protein markers Underline: CITE-seq; Bold: key reported than paper., bAbbreviations: BRCA, breast cancer; CAF, cancer-associated macrophage; CITE-seq, indexing transcriptomes epitopes sequencing; CRC, colorectal CyTOF, Mass cytometry flight; ECM, matrix; ESCA, esophageal carcinoma; GC, gastric HCC, hepatocellular HNC, head neck i.v., intravenous; IF, immunofluorescent staining; INs-seq, intracellular staining LCM, laser capture microdissection; LYM, lymphoma; MEL, melanoma; Mets, metastasis; mIHC, multiplex immunochemistry MMY, myeloma; N/A, available; NPC, nasopharyngeal NSCLC, nonsmall lung OS, osteosarcoma; OVC, ovarian PDAC, pancreatic ductal adenocarcinoma; PRAC, prostate RCC, renal Reg-TAMs, TAMs; SARC, sarcoma; sc-MS, mass spectrometry; SEPN, spinal ependymomas; SKC, ST, transcriptomics; s.c., subcutaneous; macrophages; THCA, thyroid UCEC, uterine corpus endometrial carcinoma.AnnotationSpeciesSignatureTFCancer typeFunction/enriched pathwayAssayRefsIFN-TAMsHumanCASP1, CASP4, CCL2/3/4/7/8, CD274hi, CD40, CXCL2/3/9/10/11, IDO1, IFI6, IFIT1/2/3, IFITM1/3, IRF1, IRF7, ISG15, LAMP3, PDCD1LG2hi, TNFSF10, C1QA/C, CD38, IL4I1, IFI44LSTAT1 IRF1/7BRCACRCCRC metsGBMHCCHNCLYMMELMMYNPCNSCLCOSPDACSEPNTHCAUCECApoptosis regulatorsEnhance proliferationInflammatory responsesPromote Treg entry tumorT exhaustionImmunosuppressionColocalization exhausted T (ST, IF)Decreased antigen presentation (CyTOF)Suppressed activation (in vitro)IFN-α/γ-IFN response signature; IL2/STAT5; IL6/JAK/STAT3scRNA-seqCITE-seqmIHCSTNanoString GeoMx[12.Mulder Scholar,29.Gubin M.M. al.High-dimensional delineates lymphoid compartment during successful immune-checkpoint therapy.Cell. 175: 1014-1030Abstract (165) Scholar,32.Zavidij O. reveals compromised precursor stages myeloma.Nat. Cancer. 1: 493-506Crossref 33.Zhou intratumoral immunosuppressive osteosarcoma.Nat. Commun. 11: 6322Crossref (74) 34.Zhang Q. al.Interrogation microenvironmental ependymomas dual macrophages.Nat. 12: 6867Crossref (0) Scholar,45.Wu al.Spatiotemporal level.Cancer 134-153Crossref (10) Scholar,52.Pombo Antunes A.R. profiling glioblastoma species disease stage competition specialization.Nat. Neurosci. 595-610Crossref (78) Scholar,\81.Wu S.Z. spatially resolved cancers.Nat. Genet. 53: 1334-1347Crossref (47) Scholar,83.Pelka al.Spatially organized multicellular hubs cancer.Cell. 4734-4752Abstract (29) Scholar]CD14+, CD11b+, CD68+, PD-L1hi, PD-L2hi, CD80hi, CD86hi, MHCIIhi, CD86+, MRC1–, SIGLEC1–, HLA-DRlo, CD314+, CD107a+, CD86, TLR4, CD44 (CITE-seq)MouseCcl2/7/8, Cd274, Cxcl9/10/11, Ifit1/2/3, Ifit3, Ifitm1/3, Il7r, Isg15, Nos2, Rsad2, Tnfsf10, Stat1N/ACT26 s.c. CRCCT26 intrasplenic mets modelT3 SARC (s.c.)Orthotopic GL261 GBMIFN signaturescRNA-seqCITE-seqmIHC[29.Gubin Scholar]Inflam-TAMsHumanCCL2/3/4/5/20, CCL3L1, CCL3L3, CCL4L2, CCL4L4, CXCL1/2/3/5/8, G0S2, IL1B, IL1RN, IL6, INHBA, KLF2/6, NEDD9, PMAIP1, S100A8/A9, SPP1EGR3 IKZF1 NFKB1 NFE2L2 RELCRCCRC metsOSSEPNGCRecruiting regulating cellsCNS inflammation-associated chemokinesPromotes inflammationNeutrophil recruitment lumenT interaction (IHC)TNF signaling; WNTImmune check pointsscRNA-seqmIHCNanoString GeoMx[31.Che L.-H. metastases reprogramming preoperative chemotherapy.Cell Discovery. 7: 80Crossref (4) Scholar,33.Zhou Scholar,34.Zhang Scholar,42.Sathe genomic microenvironment.Clin. Cancer 26: 2640-2653Crossref (66) 43.Zhang al.Dissecting underlying premalignant lesions cancer.Cell 27: 1934-1947Abstract (104) 44.Yin H. map development using sequencing.Front. 12728169Crossref 45.Wu Scholar]MouseCxcl1/2/3/5/8, Ccl20, Ccl3l1, Il1rn, Il1b, G0s2, Inhba, Spp1N/ACT26 CRC CT26 modelChemokine productionImmunosuppressionscRNA-seq[45.Wu Scholar]LA-TAMsHumanACP5, AOPE, APOC1, ATF1, C1QA/B/C, CCL18, CD163, CD36, CD63, CHI3L1, CTSB/D/L, F13A1, FABP5, FOLR2, GPNMB, IRF3, LGALS3, LIPA, LPL, MACRO, MerTK, MMP7/9/12, MRC1, NR1H3, NRF1, NUPR1, PLA2G7, RNASE1, SPARC, SPP1, TFDP2, TREM2, ZEB1FOS/JUN HIF1A MAF/MAFB NR1H3 TCF4 TFECBRCACRCCRC metsGBMGCHCCHNCNPCNSCLCOSPDACPhagocytosisPromotion EMTComplement activationECM degradationAntigen processing pathwaysATP biosynthetic processesCanonical M2-like pathwaysFatty acid metabolismImmunosuppressionInflammationIron ion signalingscRNA-seqSMART-seq2CITE-seqmIHCST[12.Mulder Scholar,27.Zilionis R. cancers conserved populations individuals species.Immunity. 1317-1334Abstract (424) Scholar,28.Yang non-small differences sexes.Front. 12756722Google Scholar,30.Zhang analyses inform myeloid-targeted therapies colon 181: 442-459Abstract (246) Scholar,31.Che Scholar,50.Chen Y.P. subtypes associated prognosis carcinoma.Cell 30: 1024-1042Crossref (71) Scholar,81.Wu Scholar]CD9+, CD80+, MAF, CD163lo/-, CD206+/lo, CD71+, CD72+, CD73, ICOSL, CD40LG, Thy-1 (CITE-seq)MouseAcp5, Apoc1, Apoe, C1qa/B/C, Ccl18, Ccl8, Cd163, Cd206, Cd36, Cd63, Ctsb/d/l, Cxcl9, Fabp5, Folr2, Gpnmb, Lgals3, Macro, Mrc1, Trem2MAFCT26 Orthotopic GBM 7940b orthotopic iKras p53 PDAC metsPhagocytosisAntigen presentationFatty metabolismComplement activationscRNA-seqCITE-seqmIHC[45.Wu Scholar,46.Kemp S.B. al.Pancreatic marked complement-high blood tumor–associated macrophages.Life Alliance. 4e202000935Crossref Scholar]Angio-TAMsHumanADAM8, AREG, BNIP3, CCL2/4/20, CD300E, CD44, CD55, CEBPB, CLEC5A, CTSB, EREG, FCN1, FLT1, FN1, HES1, IL8, MIF, OLR1, PPARG, S100A8/9/12, SERPINB2, SLC2A1, SPIC, THBS1, TIMP1, VCAN, VEGFABACH1 CEBPB FOSL2 HIFA KLF5 MAF RUNX1 SPIC TEAD1 ZEB2BRCACRCCRCCRC metsESCAGBMGCHCCMELNPCNPCNSCLCOVCPDACPDAC metsRCCSEPNTHCAUCECAngiogenesisCAF interactionECM proteolysis; ECM interactionPromotion EMTHIF pathway; NF-kB Notch VEGF signalingJuxtaposed PLVAP+/DLL4+ endothelial (IF)scRNA-seqSMART-seq2CITE-seqNanoString GeoMx[25.Cheng Scholar,41.Sharma al.Onco-fetal drives carcinoma.Cell. 183: 377-394Abstract (103) Scholar,49.Raghavan al.Microenvironment drug 6119-6137Abstract Scholar,67.Zhao revealed promoted progression.J. Transl. 454Crossref Scholar]CD52hi, CD163hi, CD206hi, CXCR4+, CD354+, FOSL2, VEGFAMouseArg1, Adam8, Bnip3, Mif, Slc2a1N/AOrthotopic modelHIF signalingAngiogenesisscRNA-seqCITE-seq[52.Pombo Scholar]Reg-TAMsHumanCCL2, CD274, CD80, CHIT1, CX3CR1, HLA-A/C, HLA-DQA1/B1, HLA-DRA/B1/B5, ICOSLG, IL-10, ITGA4, LGALS9, MAC
Language: Английский
Citations
360
Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(8), P. 1304 - 1326
Published: June 22, 2023
Language: Английский
Citations
338
Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)
Published: Aug. 28, 2023
Abstract Immune-checkpoint inhibitors (ICBs), in addition to targeting CTLA-4, PD-1, and PD-L1, novel LAG-3 drugs have also been approved clinical application. With the widespread use of drug, we must deeply analyze dilemma agents seek a breakthrough treatment prospect. Over past decades, these demonstrated dramatic efficacy, especially patients with melanoma non-small cell lung cancer (NSCLC). Nonetheless, field broad concept solid tumours, non-specific indications, inseparable immune response side effects, unconfirmed progressive disease, complex regulatory networks resistance are four barriers that limit its Fortunately, successful trials ICB combination therapies, advent era oncolytic virus gene editing, technical mRNA vaccines nano-delivery systems made remarkable breakthroughs currently. In this review, enumerate mechanisms each checkpoint targets, associations between tumour mutation burden, key or signalling pathways, specific evidence efficacy classical targets new among different types put forward dialectical thoughts on drug safety. Finally, discuss importance accurate triage based recent advances predictive biomarkers diagnostic testing techniques.
Language: Английский
Citations
245
Trends in Pharmacological Sciences, Journal Year: 2020, Volume and Issue: 42(1), P. 60 - 73
Published: Nov. 27, 2020
L-Tryptophan (L-Trp) is metabolized via three pathways: the indole pathway in bacteria and kynurenine serotonin pathways mammalian cells.Disruptions L-Trp metabolism are reported several diseases making a promising therapeutic target.Manipulating an attractive strategy.Key enzymes of targets inhibitors currently undergoing clinical trials cancerology, dermatology, gastroenterology.Serotonin aryl hydrocarbon receptor (AhR) receptors targeted treatment gastrointestinal diseases, inflammation, many cancers.Next-generation probiotics producing indoles being developed for their ability to activate AhR gut. essential amino acid required protein synthesis. It undergoes extensive complex along pathways, resulting bioactive molecules acting various organs through different action mechanisms. Enzymes involved its metabolism, metabolites themselves, or receptors, represent potential targets, which subject dynamic research. Disruptions L-tryptophan neurological, metabolic, psychiatric, intestinal disorders, paving way develop drugs target it. This review will briefly describe present discuss most recent pharmacological developments targeting
Language: Английский
Citations
223
Immunity, Journal Year: 2022, Volume and Issue: 55(1), P. 14 - 30
Published: Jan. 1, 2022
Adaptive immune responses mediated by T cells and B are crucial for protective immunity against pathogens tumors. Differentiation function of require dynamic reprogramming cellular metabolism. Metabolic inputs, pathways, enzymes display remarkable flexibility heterogeneity, especially in vivo. How metabolic plasticity adaptation dictate functional specialization is fundamental to our understanding therapeutic modulation the system. Extensive progress has been made characterizing effects networks on cell fate discrete microenvironments or immunological contexts. In this review, we summarize how rewiring metabolism determines outcome adaptive vivo, with a focus metabolites, nutrients, driver genes immunometabolism instruct programming during infection, inflammation, cancer mice humans. Understanding context-dependent remodeling will manifest legitimate opportunities intervention human disease.
Language: Английский
Citations
187
Cancer Treatment Reviews, Journal Year: 2022, Volume and Issue: 110, P. 102461 - 102461
Published: Aug. 30, 2022
Strategies for unlocking immunosuppression in the tumor microenvironment have been investigated to overcome resistance first-generation immune checkpoint blockade with anti- programmed cell death protein 1 (PD-1)/ death-ligand (PD-L1) and anti-cytotoxic T-lymphocyte associated 4 (CTLA-4) agents. Indoleamine 2,3-dioxygenase (IDO) 1, an enzyme catabolizing tryptophan kynurenine, creates immunosuppressive environment preclinical studies. Early phase clinical trials investigating inhibition of IDO1, especially together blockade, provided promising results. Unfortunately, 3 trial IDO1 inhibitor epacadostat combined PD-1 pembrolizumab did not show benefit when compared monotherapy patients advanced malignant melanoma, which dampened enthusiasm IDO inhibitors. Even so, several molecules, such as aryl hydrocarbon receptor 2,3-dioxygenase, were reported additional potential targets modulation pathway, might enhance effectiveness. Furthermore, combination pathway agents inhibiting other signals, those generated by PIK3CA mutations that may accompany upregulation, be a novel way activity. Importantly, expression level varies type among same type, suggesting patient selection based on levels warranted trials.
Language: Английский
Citations
173
Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(8), P. 510 - 525
Published: July 9, 2021
Language: Английский
Citations
155
Current Opinion in Immunology, Journal Year: 2021, Volume and Issue: 70, P. 7 - 14
Published: Jan. 8, 2021
Language: Английский
Citations
153
Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(12), P. 786 - 802
Published: Sept. 28, 2021
Language: Английский
Citations
144