Type I interferon signaling induces melanoma cell-intrinsic PD-1 and its inhibition antagonizes immune checkpoint blockade.

Programmed Cell Death 1 Receptor / metabolism Melanoma / drug therapy Humans Receptor, Interferon alpha-beta / metabolism Immune Checkpoint Inhibitors / pharmacology Signal Transduction / drug effects Animals Cell Line, Tumor Mice Interferon Type I / metabolism STAT1 Transcription Factor / metabolism Interferon-Stimulated Gene Factor 3, gamma Subunit / metabolism Interferon-beta / metabolism Gene Expression Regulation, Neoplastic / drug effects Janus Kinases / metabolism Mice, Inbred C57BL Interferon-alpha / pharmacology Female

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
26 Aug 2024
Historique:
received: 09 01 2024
accepted: 09 08 2024
medline: 27 8 2024
pubmed: 27 8 2024
entrez: 26 8 2024
Statut: epublish

Résumé

Programmed cell death 1 (PD-1) is a premier cancer drug target for immune checkpoint blockade (ICB). Because PD-1 receptor inhibition activates tumor-specific T-cell immunity, research has predominantly focused on T-cell-PD-1 expression and its immunobiology. In contrast, cancer cell-intrinsic PD-1 functional regulation is not well understood. Here, we demonstrate induction of PD-1 in melanoma cells via type I interferon receptor (IFNAR) signaling and reversal of ICB efficacy through IFNAR pathway inhibition. Treatment of melanoma cells with IFN-α or IFN-β triggers IFNAR-mediated Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling, increases chromatin accessibility and resultant STAT1/2 and IFN regulatory factor 9 (IRF9) binding within a PD-1 gene enhancer, and leads to PD-1 induction. IFNAR1 or JAK/STAT inhibition suppresses melanoma-PD-1 expression and disrupts ICB efficacy in preclinical models. Our results uncover type I IFN-dependent regulation of cancer cell-PD-1 and provide mechanistic insight into the potential unintended ICB-neutralizing effects of widely used IFNAR1 and JAK inhibitors.

Identifiants

DOI: 10.1038/s41467-024-51496-2 PMID: 39187481
pubmed: 39187481
doi: 10.1038/s41467-024-51496-2
pii: 10.1038/s41467-024-51496-2
doi:

Substances chimiques

Programmed Cell Death 1 Receptor 0
Receptor, Interferon alpha-beta 156986-95-7
Immune Checkpoint Inhibitors 0
Interferon Type I 0
PDCD1 protein, human 0
IFNAR1 protein, human 0
STAT1 Transcription Factor 0
Interferon-Stimulated Gene Factor 3, gamma Subunit 0
Interferon-beta 77238-31-4
IRF9 protein, human 0
Janus Kinases EC 2.7.10.2
STAT1 protein, human 0
Interferon-alpha 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

7165

Subventions

Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01CA190838
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01CA247957
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01CA258637

Informations de copyright

© 2024. The Author(s).

Références

Sharma, P. et al. The next decade of immune checkpoint therapy. Cancer Discov. 11, 838–857 (2021).
pubmed: 33811120 doi: 10.1158/2159-8290.CD-20-1680
Tumeh, P. C. et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515, 568–571 (2014).
pubmed: 25428505 pmcid: 4246418 doi: 10.1038/nature13954
Juneja, V. R. et al. PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity. J. Exp. Med. 214, 895–904 (2017).
pubmed: 28302645 pmcid: 5379970 doi: 10.1084/jem.20160801
Gill, A. L. et al. PD-1 blockade increases the self-renewal of stem-like CD8 T cells to compensate for their accelerated differentiation into effectors. Sci. Immunol. 8, eadg0539 (2023).
pubmed: 37624909 doi: 10.1126/sciimmunol.adg0539
Patsoukis, N., Wang, Q., Strauss, L. & Boussiotis, V. A. Revisiting the PD-1 pathway. Sci. Adv. 6, eabd2712 (2020).
pubmed: 32948597 pmcid: 7500922 doi: 10.1126/sciadv.abd2712
Sharpe, A. H. & Pauken, K. E. The diverse functions of the PD1 inhibitory pathway. Nat. Rev. Immunol. 18, 153–167 (2018).
pubmed: 28990585 doi: 10.1038/nri.2017.108
Schett, G., Elewaut, D., McInnes, I. B., Dayer, J.-M. & Neurath, M. F. How Cytokine Networks Fuel Inflammation: Toward a cytokine-based disease taxonomy. Nat. Med. 19, 822–824 (2013).
pubmed: 23836224 doi: 10.1038/nm.3260
Boussiotis, V. A. Molecular and biochemical aspects of the PD-1 checkpoint pathway. N. Engl. J. Med. 375, 1767–1778 (2016).
pubmed: 27806234 pmcid: 5575761 doi: 10.1056/NEJMra1514296
Kinter, A. L. et al. The common gamma-chain cytokines IL-2, IL-7, IL-15, and IL-21 induce the expression of programmed death-1 and its ligands. J. Immunol. 181, 6738–6746 (2008).
pubmed: 18981091 doi: 10.4049/jimmunol.181.10.6738
Hanna, B. S. et al. Interleukin-10 receptor signaling promotes the maintenance of a PD-1(int) TCF-1(+) CD8(+) T cell population that sustains anti-tumor immunity. Immunity 54, 2825–2841.e2810 (2021).
pubmed: 34879221 doi: 10.1016/j.immuni.2021.11.004
Francisco, L. M., Sage, P. T. & Sharpe, A. H. The PD-1 pathway in tolerance and autoimmunity. Immunol. Rev. 236, 219–242 (2010).
pubmed: 20636820 pmcid: 2919275 doi: 10.1111/j.1600-065X.2010.00923.x
Park, B. V. et al. TGFβ1-mediated SMAD3 enhances PD-1 Expression on antigen-specific T cells in cancer. Cancer Discov. 6, 1366–1381 (2016).
pubmed: 27683557 pmcid: 5295786 doi: 10.1158/2159-8290.CD-15-1347
Voron, T. et al. VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors. J. Exp. Med. 212, 139–148 (2015).
pubmed: 25601652 pmcid: 4322048 doi: 10.1084/jem.20140559
Terawaki, S. et al. IFN-α directly promotes programmed cell death-1 transcription and limits the duration of T cell-mediated immunity. J. Immunol. 186, 2772–2779 (2011).
pubmed: 21263073 doi: 10.4049/jimmunol.1003208
Garcia-Diaz, A. et al. Interferon receptor signaling pathways regulating PD-L1 and PD-L2 Expression. Cell Rep. 19, 1189–1201 (2017).
pubmed: 28494868 pmcid: 6420824 doi: 10.1016/j.celrep.2017.04.031
Lee, S. J. et al. Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-gamma-induced upregulation of B7-H1 (CD274). FEBS Lett. 580, 755–762 (2006).
pubmed: 16413538 doi: 10.1016/j.febslet.2005.12.093
Loke, P. & Allison, J. P. PD-L1 and PD-L2 are differentially regulated by Th1 and Th2 cells. Proc. Natl Acad. Sci. 100, 5336–5341 (2003).
pubmed: 12697896 pmcid: 154346 doi: 10.1073/pnas.0931259100
Peng, Q. et al. PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade. Nat. Commun. 11, 4835 (2020).
pubmed: 32973173 pmcid: 7518441 doi: 10.1038/s41467-020-18570-x
Jacquelot, N. et al. Sustained Type I interferon signaling as a mechanism of resistance to PD-1 blockade. Cell Res. 29, 846–861 (2019).
pubmed: 31481761 pmcid: 6796942 doi: 10.1038/s41422-019-0224-x
Shin, D. S. et al. Primary resistance to PD-1 blockade mediated by JAK1/2 mutations. Cancer Discov. 7, 188–201 (2017).
pubmed: 27903500 doi: 10.1158/2159-8290.CD-16-1223
Zaretsky, J. M. et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N. Engl. J. Med. 375, 819–829 (2016).
pubmed: 27433843 pmcid: 5007206 doi: 10.1056/NEJMoa1604958
Ayers, M. et al. IFN-gamma-related mRNA profile predicts clinical response to PD-1 blockade. J. Clin. Invest. 127, 2930–2940 (2017).
pubmed: 28650338 pmcid: 5531419 doi: 10.1172/JCI91190
Grasso, C. S. et al. Conserved Interferon-gamma signaling drives clinical response to immune checkpoint blockade therapy in melanoma. Cancer Cell 38, 500–515.e503 (2020).
pubmed: 32916126 pmcid: 7872287 doi: 10.1016/j.ccell.2020.08.005
Klement, J. D. et al. Tumor PD-L1 engages myeloid PD-1 to suppress type I interferon to impair cytotoxic T lymphocyte recruitment. Cancer Cell 41, 620–636.e629 (2023).
pubmed: 36917954 pmcid: 10150625 doi: 10.1016/j.ccell.2023.02.005
Platanias, L. C. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat. Rev. Immunol. 5, 375–386 (2005).
pubmed: 15864272 doi: 10.1038/nri1604
Saleiro, D. & Platanias, L. C. Interferon signaling in cancer. Non-canonical pathways and control of intracellular immune checkpoints. Semin. Immunol. 43, 101299 (2019).
pubmed: 31771762 pmcid: 8177745 doi: 10.1016/j.smim.2019.101299
Stebbing, J. & Lauschke, V. M. JAK inhibitors - more than just Glucocorticoids. N. Engl. J. Med. 385, 463–465 (2021).
pubmed: 34320294 pmcid: 8362590 doi: 10.1056/NEJMe2108667
Morand, E. F. et al. Trial of Anifrolumab in active systemic Lupus Erythematosus. N. Engl. J. Med. 382, 211–221 (2020).
pubmed: 31851795 doi: 10.1056/NEJMoa1912196
Guttman-Yassky, E. et al. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials. Lancet 397, 2151–2168 (2021).
pubmed: 34023008 doi: 10.1016/S0140-6736(21)00588-2
Papp, K. et al. Phase 2 trial of selective Tyrosine Kinase 2 inhibition in Psoriasis. N. Engl. J. Med. 379, 1313–1321 (2018).
pubmed: 30205746 doi: 10.1056/NEJMoa1806382
Rosmarin, D. et al. Two Phase 3, randomized, controlled trials of Ruxolitinib cream for Vitiligo. N. Engl. J. Med. 387, 1445–1455 (2022).
pubmed: 36260792 doi: 10.1056/NEJMoa2118828
Vaengebjerg, S., Skov, L., Egeberg, A. & Loft, N. D. Prevalence, incidence, and risk of cancer in patients with Psoriasis and Psoriatic Arthritis: A systematic review and meta-analysis. JAMA Dermatol. 156, 421–429 (2020).
pubmed: 32074260 pmcid: 7042857 doi: 10.1001/jamadermatol.2020.0024
Gordon, S. R. et al. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature 545, 495–499 (2017).
pubmed: 28514441 pmcid: 5931375 doi: 10.1038/nature22396
Helmink, B. A. et al. B cells and tertiary lymphoid structures promote immunotherapy response. Nature 577, 549–555 (2020).
pubmed: 31942075 pmcid: 8762581 doi: 10.1038/s41586-019-1922-8
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
Martins, C. et al. Tumor cell-intrinsic PD-1 promotes Merkel cell carcinoma growth by activating downstream mTOR-mitochondrial ROS signaling. Sci. Adv. 10, eadi2012 (2024).
pubmed: 38241371 pmcid: 10798567 doi: 10.1126/sciadv.adi2012
Kleffel, S. et al. Melanoma cell-intrinsic PD-1 Receptor functions promote tumor growth. Cell 162, 1242–1256 (2015).
pubmed: 26359984 pmcid: 4700833 doi: 10.1016/j.cell.2015.08.052
Martins, C. et al. Distinct antibody clones detect PD-1 checkpoint expression and block PD-L1 interactions on live murine melanoma cells. Sci. Rep. 12, 12491 (2022).
pubmed: 35864188 pmcid: 9304406 doi: 10.1038/s41598-022-16776-1
Clark, C. A. et al. Tumor-Intrinsic PD-L1 Signals Regulate Cell Growth, Pathogenesis, and Autophagy in Ovarian Cancer and Melanoma. Cancer Res. 76, 6964–6974 (2016).
pubmed: 27671674 pmcid: 5228566 doi: 10.1158/0008-5472.CAN-16-0258
Cao, Z. et al. An unexpected role for p53 in regulating cancer cell-intrinsic PD-1 by acetylation. Sci. Adv. 7, eabf4148 (2021).
pubmed: 33789902 pmcid: 8011965 doi: 10.1126/sciadv.abf4148
Sanlorenzo, M. et al. BRAF and MEK inhibitors increase PD-1-positive Melanoma cells leading to a potential lymphocyte-independent synergism with anti-PD-1 antibody. Clin. Cancer Res 24, 3377–3385 (2018).
pubmed: 29650750 doi: 10.1158/1078-0432.CCR-17-1914
Yang, S. et al. m(6)A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade. Nat. Commun. 10, 2782 (2019).
pubmed: 31239444 pmcid: 6592937 doi: 10.1038/s41467-019-10669-0
Li, H. et al. Programmed cell death-1 (PD-1) checkpoint blockade in combination with a mammalian target of rapamycin inhibitor restrains hepatocellular carcinoma growth induced by hepatoma cell-intrinsic PD-1. Hepatol 66, 1920–1933 (2017).
doi: 10.1002/hep.29360
Du, S. et al. Blockade of Tumor-Expressed PD-1 promotes lung cancer growth. Oncoimmunology 7, e1408747 (2018).
pubmed: 29632720 pmcid: 5889288 doi: 10.1080/2162402X.2017.1408747
Wang, X. et al. Tumor cell-intrinsic PD-1 receptor is a tumor suppressor and mediates resistance to PD-1 blockade therapy. Proc. Natl Acad. Sci. 117, 6640–6650 (2020).
pubmed: 32161124 pmcid: 7104341 doi: 10.1073/pnas.1921445117
Ierano, C. et al. In PD-1+ human colon cancer cells NIVOLUMAB promotes survival and could protect tumor cells from conventional therapies. J. Immunother. Cancer 10, e004032 (2022).
pubmed: 35246475 pmcid: 8900051 doi: 10.1136/jitc-2021-004032
D’Alterio, C. et al. Targeting CXCR4 potentiates anti-PD-1 efficacy modifying the tumor microenvironment and inhibiting neoplastic PD-1. J. Exp. Clin. Cancer Res. 38, 432 (2019).
pubmed: 31661001 pmcid: 6819555 doi: 10.1186/s13046-019-1420-8
Gao, M. et al. Direct therapeutic targeting of immune checkpoint PD-1 in pancreatic cancer. Br. J. Cancer 120, 88–96 (2019).
pubmed: 30377341 doi: 10.1038/s41416-018-0298-0
Mirzaei, R. et al. PD-1 independent of PD-L1 ligation promotes glioblastoma growth through the NFκB pathway. Sci. Adv. 7, eabh2148 (2021).
pubmed: 34739319 pmcid: 8570610 doi: 10.1126/sciadv.abh2148
Tirosh, I. et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352, 189–196 (2016).
pubmed: 27124452 pmcid: 4944528 doi: 10.1126/science.aad0501
Biermann, J. et al. Dissecting the treatment-naive ecosystem of human melanoma brain metastasis. Cell 185, 2591–2608.e2530 (2022).
pubmed: 35803246 pmcid: 9677434 doi: 10.1016/j.cell.2022.06.007
Liu, H. et al. Tumor-derived IFN triggers chronic pathway agonism and sensitivity to ADAR loss. Nat. Med 25, 95–102 (2019).
pubmed: 30559422 doi: 10.1038/s41591-018-0302-5
Wang, H. et al. Tumor immunological phenotype signature-based high-throughput screening for the discovery of combination immunotherapy compounds. Sci. Adv. 7, eabd7851 (2021).
pubmed: 33523948 pmcid: 10964968 doi: 10.1126/sciadv.abd7851
Liu, N. et al. Supplementation with alpha-ketoglutarate improved the efficacy of anti-PD1 melanoma treatment through epigenetic modulation of PD-L1. Cell Death Dis. 14, 170 (2023).
pubmed: 36854755 pmcid: 9974984 doi: 10.1038/s41419-023-05692-5
Zemek, R. M. et al. Temporally restricted activation of IFNbeta signaling underlies response to immune checkpoint therapy in mice. Nat. Commun. 13, 4895 (2022).
pubmed: 35986006 pmcid: 9390963 doi: 10.1038/s41467-022-32567-8
Luo, N. et al. Melanoma response to anti-PD-L1 immunotherapy requires JAK1 signaling, but not JAK2. Oncoimmunology 7, e1438106 (2018).
pubmed: 29872580 pmcid: 5975601 doi: 10.1080/2162402X.2018.1438106
Davar, D. et al. Phase Ib/II Study of Pembrolizumab and Pegylated-Interferon Alfa-2b in Advanced Melanoma. J. Clin. Oncol. 36, JCO1800632 (2018).
pubmed: 30359157 doi: 10.1200/JCO.18.00632
Fu, J. et al. STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade. Sci. Transl. Med. 7, 283ra252 (2015).
doi: 10.1126/scitranslmed.aaa4306
Razaghi, A., Durand-Dubief, M., Brusselaers, N. & Bjornstedt, M. Combining PD-1/PD-L1 blockade with type I interferon in cancer therapy. Front. Immunol. 14, 1249330 (2023).
pubmed: 37691915 pmcid: 10484344 doi: 10.3389/fimmu.2023.1249330
Lu, C. et al. Type I interferon suppresses tumor growth through activating the STAT3-granzyme B pathway in tumor-infiltrating cytotoxic T lymphocytes. J. Immunother. Cancer 7, 157 (2019).
pubmed: 31228946 pmcid: 6589175 doi: 10.1186/s40425-019-0635-8
Boukhaled, G. M., Harding, S. & Brooks, D. G. Opposing roles of Type I Interferons in cancer immunity. Annu. Rev. Pathol. 16, 167–198 (2021).
pubmed: 33264572 doi: 10.1146/annurev-pathol-031920-093932
Schatton, T. et al. Inhibition of melanoma cell-intrinsic Tim-3 stimulates MAPK-dependent Tumorigenesis. Cancer Res. 82, 3774–3784 (2022).
pubmed: 35980306 pmcid: 9598011 doi: 10.1158/0008-5472.CAN-22-0970
Buenrostro, J. D., Wu, B., Chang, H. Y. & Greenleaf, W. J. ATAC-seq: A method for assaying chromatin accessibility genome-wide. Curr. Protoc. Mol. Biol. 109, 21 29 21–21 29 29 (2015).
Ramsey, M. R., He, L., Forster, N., Ory, B. & Ellisen, L. W. Physical association of HDAC1 and HDAC2 with p63 mediates transcriptional repression and tumor maintenance in squamous cell carcinoma. Cancer Res. 71, 4373–4379 (2011).
pubmed: 21527555 pmcid: 3129427 doi: 10.1158/0008-5472.CAN-11-0046
Shen, H. et al. Selective suppression of melanoma lacking IFN-gamma pathway by JAK inhibition depends on T cells and host TNF signaling. Nat. Commun. 13, 5013 (2022).
pubmed: 36008408 pmcid: 9411168 doi: 10.1038/s41467-022-32754-7

Auteurs

Julia Holzgruber (J)

Department of Dermatology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA.
Program of Glyco-Immunology and Oncology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Department of Dermatology and Venereology, Medical Faculty, Johannes Kepler University, 4040, Linz, Austria.
ORCID: 0000-0002-7804-9387

Christina Martins (C)

Department of Dermatology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA.
Program of Glyco-Immunology and Oncology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
ORCID: 0000-0002-9160-1017

Zsofi Kulcsar (Z)

Department of Dermatology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA.
Program of Glyco-Immunology and Oncology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Center for Skin Diseases, Clinic for Dermatooncology and Phlebology, University Hospital Bonn, 53127, Bonn, Germany.

Alexandra Duplaine (A)

Department of Dermatology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA.
Centre Hospitalier Universitaire de Bordeaux, Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, UMR 5164, 33000, Bordeaux, France.

Erik Rasbach (E)

Department of Dermatology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA.
Program of Glyco-Immunology and Oncology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Department of Surgery, University Hospital Mannheim, 68167, Mannheim, Germany.

Laure Migayron (L)

Department of Dermatology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA.
Program of Glyco-Immunology and Oncology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
ORCID: 0000-0003-2003-1923

Praveen Singh (P)

Department of Dermatology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA.
Program of Glyco-Immunology and Oncology, Brigham and Women's Hospital, Boston, MA, 02115, USA.

Edith Statham (E)

Department of Dermatology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA.

Jennifer Landsberg (J)

Center for Skin Diseases, Clinic for Dermatooncology and Phlebology, University Hospital Bonn, 53127, Bonn, Germany.

Katia Boniface (K)

CNRS, ImmunoConcEpT, University of Bordeaux, UMR 5164, 33000, Bordeaux, France.
ORCID: 0000-0003-4428-1222

Julien Seneschal (J)

Centre Hospitalier Universitaire de Bordeaux, Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, UMR 5164, 33000, Bordeaux, France.
CNRS, ImmunoConcEpT, University of Bordeaux, UMR 5164, 33000, Bordeaux, France.
ORCID: 0000-0003-1139-0908

Wolfram Hoetzenecker (W)

Department of Dermatology and Venereology, Medical Faculty, Johannes Kepler University, 4040, Linz, Austria.
ORCID: 0000-0003-4710-0642

Emma L Berdan (EL)

Bioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
ORCID: 0000-0002-6435-4604

Shannan Ho Sui (S)

Bioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
ORCID: 0000-0002-6191-4709

Matthew R Ramsey (MR)

Department of Dermatology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA.

Steven R Barthel (SR)

Department of Dermatology, Brigham and Women's Hospital, Boston, MA, 02115, USA. sbarthel@bwh.harvard.edu.
Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA. sbarthel@bwh.harvard.edu.
Program of Glyco-Immunology and Oncology, Brigham and Women's Hospital, Boston, MA, 02115, USA. sbarthel@bwh.harvard.edu.
ORCID: 0000-0003-2107-4570

Tobias Schatton (T)

Department of Dermatology, Brigham and Women's Hospital, Boston, MA, 02115, USA. tschatton@bwh.harvard.edu.
Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA. tschatton@bwh.harvard.edu.
Program of Glyco-Immunology and Oncology, Brigham and Women's Hospital, Boston, MA, 02115, USA. tschatton@bwh.harvard.edu.
Department of Medicine, Boston Children's Hospital, Boston, MA, 02115, USA. tschatton@bwh.harvard.edu.
ORCID: 0000-0003-1386-680X

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Antigènes de différenciation › Antigènes de différenciation des lymphocytes T › Récepteur-1 de mort cellulaire programmée › Type I interferon signaling induces melanoma...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Naevus et mélanomes › Mélanome › Type I interferon signaling induces melanoma...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Type I interferon signaling induces melanoma...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux cytokines › Récepteur interféron › Récepteur à l'interféron alpha-bêta › Type I interferon signaling induces melanoma...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Antinéoplasiques immunologiques › Inhibiteurs de points de contrôle immunitaires › Type I interferon signaling induces melanoma...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Type I interferon signaling induces melanoma...
questionsmedicales.fr › Eucaryotes › Animaux › Type I interferon signaling induces melanoma...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Type I interferon signaling induces melanoma...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Type I interferon signaling induces melanoma...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interférons › Interféron de type I › Type I interferon signaling induces melanoma...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription STAT › Facteur de transcription STAT-1 › Type I interferon signaling induces melanoma...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Complexe ISGF3 › Sous-unité gamma du complexe ISGF3 › Type I interferon signaling induces melanoma...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interférons › Interféron de type I › Interféron bêta › Type I interferon signaling induces melanoma...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Type I interferon signaling induces melanoma...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-tyrosine kinases › Janus kinases › Type I interferon signaling induces melanoma...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Type I interferon signaling induces melanoma...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interférons › Interféron de type I › Interféron alpha › Type I interferon signaling induces melanoma...