Emerging roles of type 1 innate lymphoid cells in tumour pathogenesis and cancer immunotherapy

Exploration of Targeted Anti-tumor Therapy, Journal Year: 2024, Volume and Issue: 5(2), P. 296 - 315

Published: April 23, 2024

Innate lymphoid cells (ILCs) are the most recently discovered class of innate immune found to have prominent roles in various human immune-related pathologies such as infection and autoimmune diseases. However, their role cancer was largely unclear until recently, where several emerging studies over past few years unanimously demonstrate ILCs be critical players tumour immunity. Being counterpart T cells, potent cytokine producers through which they orchestrate overall response upstream adaptive immunity thereby modulating cell function. Out major ILC subsets, ILC1s gained significant traction potential immunotherapeutic candidates due central involvement with anti-tumour type 1 response. well-established interferon γ (IFNγ), exert direct cytotoxicity against interleukin-15 (IL-15). advanced diseases, an exhausted phenotype microenvironment (TME) impaired effector functions, characterised by decreased responsiveness cytokines reduced IFNγ production. Tumour produce immunomodulatory transforming growth factor β (TGFβ) IL-23, these suppress ILC1 actfivities converts pro-tumoural ILC3s respectively, resulting disease progression. This review provides a comprehensive overview immunity, discusses exciting prospects harnessing for immunotherapy, either alone or combination cytokine-based treatment. The targeting system may surmount limitations associated cell-based strategies used clinic currently, overcome resistance.

Language: Английский

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Circulating innate lymphoid cells (cILCs): Unconventional lymphocytes with hidden talents

Journal of Allergy and Clinical Immunology, Journal Year: 2024, Volume and Issue: 154(3), P. 523 - 536

Published: July 24, 2024

Innate lymphoid cells (ILCs) are a group of lymphocytes that devoid antigen-specific receptors and mainly found in tissues. The subtypes ILC1, 2, 3 mirror T-cell functionality terms cytokine production expression key transcription factors. Although the majority ILCs tissue (tILCs), they have also been described within circulation (cILCs). As result their better accessibility putative prognostic value, human cILCs getting more attention clinical research. However, many aspects functionally distinct from tILC counterparts. In fact, ILC subsets circulation, only for cILC2s could clear functional correspondence to counterparts be established. Indeed, emerging as major driver allergic reactions with particular role asthma. contrast, recent studies revealed cILC1s cILC3s predominantly an immature state constitute progenitors natural killer ILCs, respectively. We provide overview about phenotype function different cILC compared tILCs health disease, including transcriptomic signatures, frequency dynamics, potential value. Furthermore, we will highlight dynamics NKp44+ ILC3 subset, which emerges marker peripheral blood inflammatory bowel disease leukemia. immune system consists plethora belonging either innate or adaptive branch, where each cell population has widely frequencies. Within lineage, CD3+ T cells, CD19+ B CD94+ (NK) account over 95% all circulating lymphocytes.1Apoil P.A. Puissant-Lubrano B. Congy-Jolivet N. Peres M. Tkaczuk J. Roubinet F. et al.Reference values T, NK lymphocyte subpopulations adults.Data Brief. 2017; 12: 400-404Abstract Full Text PDF PubMed Scopus (28) Google Scholar,2Kokuina E. Breff-Fonseca M.C. Villegas-Valverde C.A. Mora-Díaz I. Normal healthy Cuban adults.MEDICC Rev. 2019; 21: 16-21PubMed Scholar addition, last 2 decades, several rare populations were discovered, lack abovementioned lineage defining surface express IL-7 receptor (IL-7R, CD127). These CD127-expressing collectively named comprise phenotypically subsets: ILC2, ILC3. Each subset established CD4+ helper subsets3Spits H. Artis D. Colonna Diefenbach A. Di Santo J.P. Eberl G. al.Innate cells—a proposal uniform nomenclature.Nat Rev Immunol. 2013; 13: 145-149Crossref (1940) Scholar: ILC1s secrete IFN-γ factor (TF) T-bet mirroring TH1 functionality,4Bernink J.H. Peters C.P. Munneke te Velde A.A. Meijer S.L. Weijer K. al.Human type 1 accumulate inflamed mucosal tissues.Nat 14: 221-229Crossref (826) ILC2s IL-5, IL-13, well some IL-4 TF GATA-3 similar TH2 cells,5Mjösberg J.M. Trifari S. Crellin N.K. van Drunen C.M. Piet IL-25– IL-33–responsive defined by CRTH2 CD161.Nat 2011; 1055Crossref (967) ILC3s divided into according NKp44 secreting IL-22 (NKp44+) IL-17A/IL-17F (NKp44−).6Hoorweg Cornelissen Aparicio-Domingo P. Papazian Kazemier al.Functional differences between NKp44− RORC+ cells.Front 2012; 3: 72Crossref (144) Scholar,7Marquardt Ivarsson M.A. Sundström Åkesson Martini Eidsmo L. al.Fetal CD103+ IL-17–producing represent dominant amniotic fluid.J 2016; 197: 3069-3075Crossref (0) RorγT, reminiscent TH17 cells.6Hoorweg Scholar,8Cella Fuchs Vermi W. Facchetti Otero Lennerz J.K.M. al.A provides source immunity.Nature. 2009; 457: 722-725Crossref humans, readily distinguished flow cytometry on basis c-Kit (CD117) (CD294) lineage-negative (Lin−) fraction ILC1 (CD117−CRTH2−), ILC2 (CD117+/−CRTH2+), (CD117+CRTH2−).9Bianca Bennstein Riccarda Manser Weinhold Scherenschlich Uhrberg OMIP-055: characterization neonatal blood.Cytometry 0: 427-430Crossref (15) Scholar, 10Del Zotto Vacca Moretta Quatrini CPHEN-15: comprehensive phenotyping helper-ILCs cytometry.Cytometry 2023; 103: 378-382Crossref (2) 11Krabbendam Nagasawa Spits Bal S.M. Isolation cells.Curr Protoc 2018; 122e55Crossref (17) Groundbreaking focusing mostly murine extent samples vital homeostasis barrier integrity.12Vivier cells: 10 years on.Cell. 174: 1054-1066Abstract (1397) Scholar,13Mjösberg Human cells.J Allergy Clin 138: 1265-1276Abstract (183) particular, shown important maintaining gastrointestinal (GI) tract secretion after exposition pathogens other danger signals, but commensal bacteria food components.14Bennstein S.B. Biology therapeutic cells.FEBS 2022; 289: 3967-3981Crossref (10) Scholar,15Konya V. Mjösberg graft-versus-host disease.Am J Transpl. 2015; 15: 2795-2801Abstract Hence, applications using adoptive transfer envisioned might become novel options treatment conditions such (IBD). To exploit cell-based immunotherapy, need isolated, enriched, and, if applicable, modified vitro. most accessible is blood—either (PB) umbilical cord (CB). while effector B, can isolated (cILCs) highlighted that, except cILC2s, differ greatly (tILCs) at transcriptional level.16Bennstein A.R. Noll Raba al.Umbilical blood–derived ILC1-like precursor mature KIR+NKG2A− cells.eLife. 2020; 9e55232Crossref (24) 17Lim A.I. Li Y. Lopez-Lastra Stadhouders R. Paul Casrouge al.Systemic precursors substrate differentiation.Cell. 168: 1086-1100.e10Abstract (387) 18Bennstein al.Transcriptional ILCs.Stem Cells Transl Med. 2021; 10: 867-882Crossref (14) Therefore, depending interest, tissue-resident cannot directly blood. solve this problem, alternative approaches generate vitro use described.19Bennstein Degistirici Ö. Oostendorp R.A.J. Kögler al.Efficient generation IL-22–secreting CD34+ hematopoietic mesenchymal stem niche.Front 12Google 20Ising Zimmermann al.HCMV infection niche: differential impact development versus ILC3.J 9: 10Crossref (8) 21Hernández D.C. Juelke Müller N.C. Durek Ugursu Mashreghi M.-F. al.An platform supports recapitulate ex vivo identity.Immunity. 54: 2417-2432.e5Abstract 22Van der Meer J.M.R. Bulder Kuijk C. Kleijer Verheij M.W. Omar S.Z. al.Generation allogeneic autologous toward transfer.Cytotherapy. 2024; 26: 136-144Abstract value so far largely unexplored, increasing number disease. Their ready PB CB makes them attractive candidates applications. Here hope shed light functionality, biology, cILCs, define distinguishing features mouse tILCs. Frequencies total counts generally low, making cells. Total (cILC1-3) ranges 0.1% 1% lymphocytes, count 45 per microliter blood.16Bennstein Scholar,23Uyen Pham T.X. Klumb Niehues T. Circulating children: reference evaluation immunocompromised pediatric patients.J 42: 1405-1408Crossref Scholar,24Vely Barlogis Vallentin Neven Piperoglou Ebbo al.Evidence redundancy humans.Nat 17: 1291-1299Crossref (252) Dynamic changes general, observed during aging context viral infection, autoimmunity, cancer (Table I). Genetics, ethnicity, sex, environmental factors exposure diet25Darboe Nielsen Wolf A.-S. Wildfire Danso Sonko al.Age-related African population.Front 11: 3070Crossref (18) 26Forsberg Bengtsson Eringfält Ernerudh Jenmalm GATA binding protein 3+ present higher proportions male than female neonates.J 2014; 134: 228-230.e2Abstract 27Pascal Kazakov Chevalier Dubrule Deyrat Dupin al.The neuropeptide VIP potentiates intestinal immunity response feeding.Mucosal 629-641Abstract (25) 28Seillet Luong Tellier Jacquelot Shen R.D. Hickey confers anticipatory regulating activity.Nat 168-177Crossref (134) 29Talbot Hahn Kroehling Nguyen Littman D.R. Feeding-dependent neuron–ILC3 circuit regulates barrier.Nature. 579: 575-580Crossref (192) play role, individual quantitative contribution these frequencies currently unclear.Table IReported diseasesType diseaseDiseaseChange lymphocytes/CD45 (% change)NKp44+ cILC3sStudyTotal %cILC1scILC2scILC3sAutoimmune diseaseCrohn diseaseNDHLA-DR+ ↑∗Activated phenotype.SLAMF1+ phenotype.CD45RA+ phenotype.Present48Mazzurana Bonfiglio Forkel D'Amato Halfvarson Crohn's associated activation cells.Inflamm Bowel Dis. ScholarCrohn ulcerative colitis↓→↓↓Present47Creyns Jacobs Verstockt Cremer Ballet Vandecasteele al.Biological therapy patients partly restores subtype equilibrium.Front 11Google ScholarMultiple sclerosis treated anti-CD25→→→→ND52Gillard G.O. Saenz S.A. Huss D.J. Fontenot J.D. unchanged DAC HYP therapy.J Neuroimmunol. 294: 41-45Abstract ScholarSystemic sclerosisND↑→↓Present45Roan Stoklasek T.A. Whalen Molitor J.A. Bluestone Buckner al.CD4+ form increased systemic sclerosis.J 196: 2051-2062Crossref ScholarPsoriasis vulgaris + atherosclerosis/obesity↑↑↑↑ND43Schielke Hobelsberger Steininger Strunk Blau al.Metabolic syndrome psoriasis upregulation CXCL16 monocytes dysbalance 13Crossref (6) vulgarisNDNDNDNDPresent99Teunissen M.B.M. Bernink Spuls P.I. Res P.C.M. al.Composition skin: enrichment NCR+ lesional skin Invest Dermatol. 2351-2360Abstract (266) arthritis↓↓↓↓Absent44Soare Weber Maul Rauber Gheorghiu A.M. Luber al.Cutting edge: imbalanced psoriatic arthritis.J 200: 1249-1254Crossref (not specified further)NDNDNDNDPresent100Villanova Flutter Tosi Grys Sreeneebus Perera G.K. al.Characterization demonstrates increase psoriasis.J 984-991Abstract (320) ScholarAtopic dermatitisNDNDNDNDVery low frequencies100Villanova ScholarLupus nephritis↓↓→↑ND51Ryu Lee E.Y. Kim D.K. Y.S. Chung D.H. al.Reduction results impaired lupus nephritis.Arthritis Ther. 22: 63Crossref ScholarANCA↓↓↓↓ND49Braudeau Amouriaux Néel Herbreteau Salabert Rimbert al.Persistent deficiency mucosal-associated invariant (MAIT) ANCA-associated vasculitis.J Autoimmun. 70: 73-79Crossref ScholarANCA acute phase↑↓↓ND49Braudeau ScholarANCA→→↓→ND50Fazekas Moreno-Olivera Kelly O'Hara Murray Kennedy al.Alterations small vessel vasculitis non-specific manifestations renal injury.Clin Exp 191: 180-188Crossref ScholarRheumatoid arthritisNDNDNDNDPresent105Ren Feng Z. Lv Chen X. Natural killer-22 synovial fluid rheumatoid arthritis interleukin 22 tumor necrosis factor-α.J Rheumatol. 38: 2112-2118Crossref (40) arthritis→↓↑↑ND109Wang Rui Shan Xue Dong al.Imbalance Th17, Treg, arthritis.Clin 41: 3837-3849Crossref (16) ScholarOLP↑ Highest erosive OLP↑↓ → (counts)→Present (nonerosive OLP)101Wang Z.M. Zhang Wang Zhou tipped balance ILC1/ILC2 oral lichen planus related cytokines.Front Cell Dev Biol. 9725169Google ScholarAxial spondyloarthritisNDNDNDNDPresent, highest dyslipidemia102Min H.K. Moon S.Y. C.R. al.Expanded IL-22+ oxidized LDL-C pathogenesis axial spondyloarthritis dyslipidaemia.Immune Netw. e43Crossref ScholarPemphigus vulgaris↓↑→↓ND46Zhu Su Deng Wu Liu dysregulation autoantibodies pemphigus vulgaris.Int Immunopharmacol. 117109921Crossref (3) ScholarAsthma/allergyAsthma (sputum)NDND↑NDND55Miao Q. Y.G. Ren Y.X. Guan al.Seasonal variation mugwort-allergic asthmatics outside pollen season.Allergy Asthma 6Crossref ScholarAsthma (sputum)↑↑↑↑Present54Kim Chang Bae Sohn K.H. Cho S.H. crosstalk asthmatic airways: coordinate polarization lung macrophages.J 143: 1769-1782.e11Abstract ScholarSmokers vs nonsmokers sputum→→→↑Present110Ham Park I.W. Choi B.W. al.Cigarette smoke aggravates asthma inducing memory-like cells.Nat Commun. 3852Crossref blood→→→→ND110Ham ScholarViral infectionCOVID-19↓→→, CD117+↓, CD117− ↑→ND111Forte Pellegrino R.M. Trabanelli Tonetti Ricci Cenerenti al.Circulating extracellular particles severe COVID-19 show altered profiling cell–modulating ability.Front 14Crossref ScholarCOVID-19 moderate↓ NS→↑↓ND30García Kokkinou Carrasco García Parrot Palma Medina L.M. Maleki K.T. composition associates severity.Clin 9e1224Crossref (54) severe↓→→↓ND30García ScholarAcute HIV↓↓↓↓Absent31Kløverpris H.N. Kazer S.W. Mabuka Wellmann Ndhlovu depleted irreversibly HIV-1 absence suppression.Immunity. 44: 391-405Abstract (115) Scholar,32Nabatanzi Cose Joloba Jones S.R. Nakanjako Effects HIV ART monocytes, killer, cells.AIDS 7Crossref (33) ScholarTumorAML↓→↓→Present56Munneke Björklund A.T. Garming-Legert Blom al.Activated reduced susceptibility disease.Blood. 124: 812-821Crossref (191) ScholarAfter HSCT↓↓↓↓Present56Munneke ScholarMelanomaND→→→ND57Rethacker Roelens Bejar Maubec Moins-Teisserenc Caignard Specific patterns metastatic melanoma modulations immunotherapy.Cancers. 1446Crossref ScholarMelanoma ipilimumabND↓↓→ND57Rethacker ScholarOther diseasesSeptic shock (cell count)→↓↑↑ND53Carvelli Bourenne Farnarier Banzet Demerlé septic shock.Front 10Google ScholarArrows indicate ↓ reduced, ↑ increased, controls; ND, not determined reported; NS, significant; OLP, planus.∗ Activated phenotype. Open table new tab Arrows planus. age dependent: decrease significantly aging.16Bennstein 24Vely 25Darboe subsequent significant children adults24Vely further elderly adults (>63 years).16Bennstein detailed analysis cohort aged 0 18 years, recently infants (0-1 years) cILCs,23Uyen decreased schoolchildren (6-12 even adolescents (13-18 years).23Uyen Scholar,25Darboe display counts, decreasing adolescents, continuously throughout life. When taking gestational samples, early term (37 weeks) postterm (43 delivery, shedding fetal cILC1s. A correlation was cILC3s.16Bennstein childhood, cILC1 until adolescence. pertained CD5 CD161.23Uyen While showed trend toddlers (2-5 years), adolescents.23Uyen Several reductions cILC1s, respiratory coronavirus (SARS-Cov2)– immunodeficiency virus (HIV)-infected patients, reduced,30García Scholar,31Kløverpris possibly induction apoptosis.31

Language: Английский

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A Deeply Quiescent Subset of CML LSC depend on FAO yet Avoid Deleterious ROS by Suppressing Mitochondrial Complex I

Current Molecular Pharmacology, Journal Year: 2023, Volume and Issue: 17

Published: Sept. 11, 2023

Disease relapse and therapy resistance remain serious impediments to treating cancer. Leukemia stem cells (LSC) are resistant the cause of relapse. A state deep quiescence appears enable cancer (CSC) acquire new somatic mutations essential for disease progression resistance. Both normal hematopoietic (HSC) LSC share many common features, thereby complicating safe elimination LSC. recent study demonstrated that long lived oocytes exist without mitochondrial complex I (MC-1), expressing it in a developmentally regulated fashion, mitigating their vulnerability ROS. Quiescent CSC rely on FAO, expression, avoiding generation damaging ROS, similar human cells. deeper understanding biology is important development optimal strategies attain complete leukemia cures.Here, using scRNA-sequencing ATAC-seq primary chronic myelogenous (CML) patient samples, combined with bioinformatics analyses, we further examine heterogeneity previously characterized vitro imatinib-selected CD34-CD38- CML population. We utilized series functional including single-cell metabolomic Seahorse validate existence deepest quiescent initiators (LI) subset.Current revealed patients two functionally distinct states. The most deeply LI suppress expression MC-1, yet highly dependent fatty acid oxidation (FAO) metabolic requirements increased chromatin accessibility this population, all consistent an extremely primitive, stemness transcriptional signature. Importantly, specific CREB binding protein (CBP)/β-catenin antagonist ICG-001 initiates differentiation LSC, LI, decreases increasing CD34, CD38 BCR-ABL1, resensitizing them imatinib.We investigated biological aspects related ability small molecule CBP/β-catenin antagonists safely eliminate CSC. These observations may represent attractive generalizable therapeutic strategy could help develop better protocols eradicate

Language: Английский

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The role of ILC subsets in cancer

Seminars in Immunology, Journal Year: 2022, Volume and Issue: 61-64, P. 101654 - 101654

Published: Oct. 25, 2022

The family of innate lymphoid cells (ILCs) are composed five canonical subsets, NK cells, ILC1, ILC2, ILC3 and Lymphoid tissue inducer cells. ILCs have important functions in early stages immune response towards infectious agents. highly plastic enabling rapid modification their dependent on the type microbe environment to optimally counter these microbes. Data that still accumulate a pace indicate also involved immunity against tumor Paradoxically ILC subsets been shown suppressing promoting activities. In this brief review we provide snapshot our current knowledge characteristics infiltrating speculate how can be harnessed mediate anti-tumor immunity.

Language: Английский

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IL-18 and VEGF-A trigger type 2 innate lymphoid cell accumulation and pro-tumoral function in chronic myeloid leukemia

Haematologica, Journal Year: 2023, Volume and Issue: unknown

Published: April 6, 2023

Chronic myeloid leukemia (CML) is a hematologic malignancy associated to an unregulated growth of cells in bone marrow (BM) and peripheral blood (PB), characterized by the BCR-ABL1 translocation. Given known cytokine impairment leukemic niche CML, we investigated impact this microenvironmental dysregulation on innate lymphoid (ILC), whose role cancer has recently emerged. Three ILC subsets are identified based transcriptional profiles secretion. We observed that interleukin 18 (IL-18) vascular endothelial factor A (VEGF-A) increased CML patients' sera ILC2 enriched PB BM. found IL-18 drives proliferation highly express CXCR4 CXCR7 BM-homing receptors, potentially explaining their enrichment BM, respectively. Next, showed hyper-activated through tumor-derived VEGF-Adependent mechanism, which leads higher IL-13 In response IL-13, increase clonogenic capacity. Finally, discovered pro-tumoral axis involving VEGF-A, was disrupted upon tyrosine kinase inhibitor treatment, normalizing levels all these players patients responding therapy. Overall, our study uncovers involvement progression, mediated VEGF-A IL-18.

Language: Английский

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