FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3200712821> ?p ?o ?g. }

• W3200712821 endingPage "2322" @default.
• W3200712821 startingPage "2320" @default.
• W3200712821 abstract "The importance of innate immune cells in cancer promotion has been long recognized. Luci et al. (2021) show a key role for innate lymphoid cells (ILCs) in controlling precancerous skin lesions and impaired function of NK cells and ILC1s during progression to cutaneous squamous cell carcinoma (cSCC). These results, together with other findings, suggest that activation of ILCs could serve as a novel immunotherapeutic strategy against cSCC. The importance of innate immune cells in cancer promotion has been long recognized. Luci et al. (2021) show a key role for innate lymphoid cells (ILCs) in controlling precancerous skin lesions and impaired function of NK cells and ILC1s during progression to cutaneous squamous cell carcinoma (cSCC). These results, together with other findings, suggest that activation of ILCs could serve as a novel immunotherapeutic strategy against cSCC. Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer, with a significant rise in its incidence over the last decade (Que et al., 2018Que S.K.T. Zwald F.O. Schmults C.D. Cutaneous squamous cell carcinoma: incidence, risk factors, diagnosis, and staging.J Am Acad Dermatol. 2018; 78: 237-247Abstract Full Text Full Text PDF PubMed Scopus (226) Google Scholar). The tight association between cSCC risk and immunosuppression highlights the pivotal role of the immune system in regulating cSCC development and progression. Furthermore, the high efficacy of immune checkpoint blockade (ICB) for advanced cSCC treatment supports the crucial role of the immune system in controlling cSCC. Innate immune cells of lymphoid lineage (innate lymphoid cells [ILCs]) are predominantly found in barrier organs such as skin, where they play important roles in tissue homeostasis (Yang et al., 2017Yang J. Zhao L. Xu M. Xiong N. Establishment and function of tissue-resident innate lymphoid cells in the skin.Protein Cell. 2017; 8: 489-500Crossref PubMed Scopus (9) Google Scholar). Group 1 ILCs include NK cells with cytotoxic and antitumor properties as well as ILC1s that exhibit noncytotoxic helper-like features and possess the ability to produce inflammatory cytokines, including IFN-γ and TNF-α. Owing to the tumor-promoting and suppressing activities of ILCs in the tumor microenvironment (TME), modulation of ILC function provides an opportunity to design novel immunotherapeutic approaches against cancer.Clinical Implications•Targeting innate lymphoid cells (ILCs) in precancerous skin lesions provides an opportunity to prevent cutaneous squamous cell carcinoma (cSCC) development.•Novel cSCC immunotherapies that target cytokines, inhibitory receptors, and activating receptors on cSCC-infiltrating group 1 ILCs may be effective.•Promising therapeutic approaches for immune-related adverse events prevention by modulating ILCs in the affected tissues are possible. •Targeting innate lymphoid cells (ILCs) in precancerous skin lesions provides an opportunity to prevent cutaneous squamous cell carcinoma (cSCC) development.•Novel cSCC immunotherapies that target cytokines, inhibitory receptors, and activating receptors on cSCC-infiltrating group 1 ILCs may be effective.•Promising therapeutic approaches for immune-related adverse events prevention by modulating ILCs in the affected tissues are possible. Luci et al., 2021Luci C. Bihl F. Bourdely P. Khou S. Popa A. Meghraoui-Kheddar A. et al.Cutaneous squamous cell carcinoma development is associated with a temporal infiltration of ILC1 and NK cells with immune dysfunctions.J Invest Dermatol. 2021; 141: 2369-2379Abstract Full Text Full Text PDF Scopus (1) Google Scholar investigated the function of NK cells and ILC1s in mouse and human cSCC. Using skin chemical carcinogenesis and murine cSCC cell line graft models, they showed a requirement for NK cells at a precancerous stage for protection against early cSCC development. However, they detected higher NKp46+ NK cell infiltration in cSCC tumors than in the precancerous stage (Figure 1). Consistent with mouse cSCC models, they found CD56+ NKp46+ NK cells to be the most abundant ILC subset in human cSCCs. This suggests that despite their increased number, NKp46+ NK cells are unable to control cSCC progression. Ortner et al., 2017Ortner D. Tripp C.H. Komenda K. Dubrac S. Zelger B. Hermann M. et al.Langerhans cells and NK cells cooperate in the inhibition of chemical skin carcinogenesis.Oncoimmunology. 2017; 6e1260215Crossref PubMed Scopus (17) Google Scholar also showed a higher number of papillomas and increased tumor growth in the absence of NK cells in a mouse model of skin chemical carcinogenesis. These investigators showed that 7,12-dimethylbenz[a]anthracene induced cSCC by accelerating DNA damage, which was accompanied by the accumulation of NK cells, with NK1.1, NKp46, and NKG2D cell surface markers in the tumors. Luci et al., 2021Luci C. Bihl F. Bourdely P. Khou S. Popa A. Meghraoui-Kheddar A. et al.Cutaneous squamous cell carcinoma development is associated with a temporal infiltration of ILC1 and NK cells with immune dysfunctions.J Invest Dermatol. 2021; 141: 2369-2379Abstract Full Text Full Text PDF Scopus (1) Google Scholar confirmed the contribution of NK cells to cSCC immunity by showing a significant increase in chemical carcinogens‒induced papilloma numbers and tumor sizes in Nfil3−/− mice, which lacked NK and other ILC subtypes. Adoptive transfer of purified NK cells into these mice reduced tumor sizes, establishing the role of NK cells in controlling the early stages of cSCC development. Interestingly, IL-33 cytokine signaling has been proposed as a mechanism for decreased NK cell frequency and cytotoxicity in cSCC (Amôr et al., 2018Amôr N.G. de Oliveira C.E. Gasparoto T.H. Vilas Boas V.G. Perri G. Kaneno R. et al.ST2/IL-33 signaling promotes malignant development of experimental squamous cell carcinoma by decreasing NK cells cytotoxicity and modulating the intratumoral cell infiltrate.Oncotarget. 2018; 9: 30894-30904Crossref PubMed Scopus (11) Google Scholar). Lack of IL-33 receptor, ST2, was accompanied by higher expression of NKp46 and KLRG1 on NK cells as well as lower production of the inflammatory cytokines, indicating a critical role for IL-33 in promoting cSCC by impairing NK cell cytotoxicity (Amôr et al., 2018Amôr N.G. de Oliveira C.E. Gasparoto T.H. Vilas Boas V.G. Perri G. Kaneno R. et al.ST2/IL-33 signaling promotes malignant development of experimental squamous cell carcinoma by decreasing NK cells cytotoxicity and modulating the intratumoral cell infiltrate.Oncotarget. 2018; 9: 30894-30904Crossref PubMed Scopus (11) Google Scholar) (Figure 1). Unlike NK cells with a defined role in antitumor immunity and immunosurveillance against cSCC development, the role of noncytotoxic ILC1s in cancer and antitumor-immune responses is less well-characterized and is thought to be mediated by the TME (Crinier et al., 2020Crinier A. Kerdiles Y. Vienne M. Cózar B. Vivier E. Berruyer C. Multidimensional molecular controls defining NK/ILC1 identity in cancers [e-pub ahead of print].Semin Immunol. 2020; (accessed 30 March 2021)https://doi.org/10.1016/j.smim.2020.101424Crossref PubMed Scopus (5) Google Scholar). ILC1s have been proposed to participate in cancer immunoediting both at the early elimination stage, during tumor-immune equilibrium, and at the late tumor escape phase (Wagner and Koyasu, 2019Wagner M. Koyasu S. Cancer immunoediting by innate lymphoid cells.Trends Immunol. 2019; 40: 415-430Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar). ILCs abundance in the skin and mucosal tissues; their high infiltration in cancers of the barrier organs, including esophagus, stomach, lung, and colon; and their ability to secrete IFN-γ and TNF-α raise the possibility that they can play an antitumor role in cSCC development. In addition, on the basis of Luci et al., 2021Luci C. Bihl F. Bourdely P. Khou S. Popa A. Meghraoui-Kheddar A. et al.Cutaneous squamous cell carcinoma development is associated with a temporal infiltration of ILC1 and NK cells with immune dysfunctions.J Invest Dermatol. 2021; 141: 2369-2379Abstract Full Text Full Text PDF Scopus (1) Google Scholar and other publications, the enrichment of ILC2s in healthy skin versus the high infiltration of ILC1s in the precancerous papilloma stage indicates a potential plasticity in ILC regulation in the skin that may evolve from one subtype to another in response to TME signals. Importantly, ILC2s can convert to ILC1s when exposed to IL-1β and IL-12 by upregulating the T-bet transcription factor (Bal et al., 2016Bal S.M. Bernink J.H. Nagasawa M. Groot J. Shikhagaie M.M. Golebski K. et al.IL-1β, IL-4 and IL-12 control the fate of group 2 innate lymphoid cells in human airway inflammation in the lungs.Nat Immunol. 2016; 17: 636-645Crossref PubMed Scopus (270) Google Scholar; Ohne et al., 2016Ohne Y. Silver J.S. Thompson-Snipes L. Collet M.A. Blanck J.P. Cantarel B.L. et al.IL-1 is a critical regulator of group 2 innate lymphoid cell function and plasticity [published correction appears in Nat Immunol 2016;17:1005].Nat Immunol. 2016; 17: 646-655Crossref PubMed Scopus (210) Google Scholar). Furthermore, in the presence of TGFβ in the TME, NK cells downregulate Eomes transcription factor and convert to ILC1s (Gao et al., 2017Gao Y. Souza-Fonseca-Guimaraes F. Bald T. Ng S.S. Young A. Ngiow S.F. et al.Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells.Nat immunol. 2017; 18: 1004-1015Crossref PubMed Scopus (291) Google Scholar) (Figure 1). However, the precise immunopathogenesis behind these transformations and the possibility of ILC1s being able to convert to NK cells at the early precancerous stage and during cSCC development remain uncertain. NK cells and ILC1s show altered functional repertoires in cancer. Luci et al., 2021Luci C. Bihl F. Bourdely P. Khou S. Popa A. Meghraoui-Kheddar A. et al.Cutaneous squamous cell carcinoma development is associated with a temporal infiltration of ILC1 and NK cells with immune dysfunctions.J Invest Dermatol. 2021; 141: 2369-2379Abstract Full Text Full Text PDF Scopus (1) Google Scholar reported lower secretion of IFN-γ and granzymes A and B and higher expression of inflammatory cytokines such as IL-6, IL-2, and TNF-α by ILC1s at the papilloma stage, along with reduced cytotoxicity of NK cells at papilloma and tumor stage (Figure 1). Consistent with these findings, the maintenance of NKp46+ NK cells in TME has been associated with higher IFN-γ production and prevention of melanoma metastasis by increased fibronectin 1 secretion (Glasner et al., 2018Glasner A. Levi A. Enk J. Isaacson B. Viukov S. Orlanski S. et al.NKp46 receptor-mediated interferon-γ production by natural killer cells increases fibronectin 1 to alter tumor architecture and control metastasis [published correction appears in Immunity 2018;48:396–8].Immunity. 2018; 48: 107-119.e4Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar). In contrast, the upregulation of inhibitory receptors such as TIGIT, PD-1, LAG3, and CTLA4 on ILCs in the TME has been found to be associated with tumor progression (Crinier et al., 2020Crinier A. Kerdiles Y. Vienne M. Cózar B. Vivier E. Berruyer C. Multidimensional molecular controls defining NK/ILC1 identity in cancers [e-pub ahead of print].Semin Immunol. 2020; (accessed 30 March 2021)https://doi.org/10.1016/j.smim.2020.101424Crossref PubMed Scopus (5) Google Scholar). Luci et al., 2021Luci C. Bihl F. Bourdely P. Khou S. Popa A. Meghraoui-Kheddar A. et al.Cutaneous squamous cell carcinoma development is associated with a temporal infiltration of ILC1 and NK cells with immune dysfunctions.J Invest Dermatol. 2021; 141: 2369-2379Abstract Full Text Full Text PDF Scopus (1) Google Scholar showed an upregulation of inhibitory receptors CTLA4 and PD-1 on ILC1 and NK cells at the papilloma and tumor stages of cSCC development, and the authors highlighted the TIGIT-induced inhibitory axis on NK cells to be prominent in human cSCC (Figure 1). This finding is supported by the TIGIT-mediated NK cell exhaustion in cancer and the inhibition of tumor growth by blocking TIGIT, which can be a promising strategy for cSCC immunotherapy (Zhang et al., 2018Zhang Q. Bi J. Zheng X. Chen Y. Wang H. Wu W. et al.Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity.Nat Immunol. 2018; 19: 723-732Crossref PubMed Scopus (380) Google Scholar). Immune-related adverse events (irAEs) after ICB therapy affect several organs, including the skin, by mechanisms similar to those of autoimmune diseases that mostly implicate T-cell‒mediated immunopathogenesis. Considering the role of ILCs in skin inflammation and their expression of immune checkpoint receptors, the question arises whether ILCs impacted by ICB therapy could also contribute to irAEs. Finally, Luci et al., 2021Luci C. Bihl F. Bourdely P. Khou S. Popa A. Meghraoui-Kheddar A. et al.Cutaneous squamous cell carcinoma development is associated with a temporal infiltration of ILC1 and NK cells with immune dysfunctions.J Invest Dermatol. 2021; 141: 2369-2379Abstract Full Text Full Text PDF Scopus (1) Google Scholar showed the downregulation of activating receptors, including NKG2D and DNAM-1, on NK cells in cSCC tumors. However, a significantly higher percentage of NKp46+ ILC1s at the early precancerous stage than NKp46+ NK cells at the tumor stage expressed these activating receptors (Figure 1). Our findings on the significant upregulation of NKG2D ligand, MICB, on actinic keratoses treated with topical calcipotriol plus 5-fluorouracil immunotherapy suggest that group 1 ILCs may play a key role in cSCC immunoprevention (Cunningham et al., 2017Cunningham T.J. Tabacchi M. Eliane J.P. Tuchayi S.M. Manivasagam S. Mirzaalian H. et al.Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy.J Clin Invest. 2017; 127: 106-116Crossref PubMed Scopus (63) Google Scholar). Accordingly, a comprehensive examination of ILCs in human precancerous skin lesions is warranted to gain fundamental insights into how keratinocytes’ early malignant transformation is regulated by ILCs to enable optimal immunotherapeutic approaches to prevent cSCC development. Marjan Azin: http://orcid.org/0000-0001-6950-4854 Shadmehr Demehri: http://orcid.org/0000-0002-7913-2641 The authors state conflict of interest. Cutaneous Squamous Cell Carcinoma Development Is Associated with a Temporal Infiltration of ILC1 and NK Cells with Immune DysfunctionsJournal of Investigative DermatologyVol. 141Issue 10PreviewNK cells and tissue-resident innate lymphoid cells (ILCs) are innate effectors found in the skin. To investigate their temporal dynamics and specific functions throughout the development of cutaneous squamous cell carcinoma (cSCC), we combined transcriptomic and immunophenotyping analyses in mouse and human cSCCs. We identified an infiltration of NK cells and ILC1s as well as the presence of a few ILC3s. Adoptive transfer of NK cells in NK cell‒ and ILC-deficient Nfil3−/− mice revealed a role for NK cells in early control of cSCC. Full-Text PDF" @default.
• W3200712821 created "2021-09-27" @default.
• W3200712821 creator A5028567895 @default.
• W3200712821 creator A5048103643 @default.
• W3200712821 date "2021-10-01" @default.
• W3200712821 modified "2023-09-25" @default.
• W3200712821 title "Innate Lymphoid Cells: New Targets for Cutaneous Squamous Cell Carcinoma Immunotherapy" @default.
• W3200712821 cites W2343795401 @default.
• W3200712821 cites W2344906887 @default.
• W3200712821 cites W2555806035 @default.
• W3200712821 cites W2557214320 @default.
• W3200712821 cites W2594155088 @default.
• W3200712821 cites W2741163567 @default.
• W3200712821 cites W2782712404 @default.
• W3200712821 cites W2783237763 @default.
• W3200712821 cites W2808601843 @default.
• W3200712821 cites W2884126491 @default.
• W3200712821 cites W2939420808 @default.
• W3200712821 cites W3152317148 @default.
• W3200712821 doi "https://doi.org/10.1016/j.jid.2021.04.003" @default.
• W3200712821 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34560914" @default.
• W3200712821 hasPublicationYear "2021" @default.
• W3200712821 type Work @default.
• W3200712821 sameAs 3200712821 @default.
• W3200712821 citedByCount "2" @default.
• W3200712821 countsByYear W32007128212022 @default.
• W3200712821 countsByYear W32007128212023 @default.
• W3200712821 crossrefType "journal-article" @default.
• W3200712821 hasAuthorship W3200712821A5028567895 @default.
• W3200712821 hasAuthorship W3200712821A5048103643 @default.
• W3200712821 hasBestOaLocation W32007128211 @default.
• W3200712821 hasConcept C136449434 @default.
• W3200712821 hasConcept C142724271 @default.
• W3200712821 hasConcept C203014093 @default.
• W3200712821 hasConcept C2777701055 @default.
• W3200712821 hasConcept C3019992690 @default.
• W3200712821 hasConcept C47742525 @default.
• W3200712821 hasConcept C502942594 @default.
• W3200712821 hasConcept C71924100 @default.
• W3200712821 hasConcept C8891405 @default.
• W3200712821 hasConceptScore W3200712821C136449434 @default.
• W3200712821 hasConceptScore W3200712821C142724271 @default.
• W3200712821 hasConceptScore W3200712821C203014093 @default.
• W3200712821 hasConceptScore W3200712821C2777701055 @default.
• W3200712821 hasConceptScore W3200712821C3019992690 @default.
• W3200712821 hasConceptScore W3200712821C47742525 @default.
• W3200712821 hasConceptScore W3200712821C502942594 @default.
• W3200712821 hasConceptScore W3200712821C71924100 @default.
• W3200712821 hasConceptScore W3200712821C8891405 @default.
• W3200712821 hasIssue "10" @default.
• W3200712821 hasLocation W32007128211 @default.
• W3200712821 hasOpenAccess W3200712821 @default.
• W3200712821 hasPrimaryLocation W32007128211 @default.
• W3200712821 hasRelatedWork W2039597291 @default.
• W3200712821 hasRelatedWork W2078875613 @default.
• W3200712821 hasRelatedWork W2294037042 @default.
• W3200712821 hasRelatedWork W2749632265 @default.
• W3200712821 hasRelatedWork W2754140340 @default.
• W3200712821 hasRelatedWork W2900558465 @default.
• W3200712821 hasRelatedWork W2900916646 @default.
• W3200712821 hasRelatedWork W3030208661 @default.
• W3200712821 hasRelatedWork W3031062651 @default.
• W3200712821 hasRelatedWork W4386606772 @default.
• W3200712821 hasVolume "141" @default.
• W3200712821 isParatext "false" @default.
• W3200712821 isRetracted "false" @default.
• W3200712821 magId "3200712821" @default.
• W3200712821 workType "article" @default.