775
Views
4
CrossRef citations to date
0
Altmetric
Review

The non-linearity of RAF-MEK signaling in dendritic cells

&
Pages 2249-2259 | Received 10 Jan 2020, Accepted 10 Jul 2020, Published online: 04 Aug 2020

References

  • Melnikova I, Golden J. Targeting protein kinases. Nat Rev Drug Discov. 2004;3(12):993–994.
  • Hopkins AL, Groom CR. The druggable genome. Nat Rev Drug Discov. 2002;1(9):727–730.
  • Wu P, Nielsen TE, Clausen MH. Small-molecule kinase inhibitors: an analysis of FDA-approved drugs. Drug Discov Today. 2016;21(1):5–10.
  • Pandey R, Kapur R. Kinase inhibitors in clinical practice: an expanding world. J Allergy Clin Immunol. 2018;141(2):522–524.
  • Roskoski R Jr. Properties of FDA-approved small molecule protein kinase inhibitors. Pharmacol Res. 2019;144:19–50.
  • Sogi KM, Lien KA, Johnson JR, et al. The tyrosine kinase inhibitor gefitinib restricts mycobacterium tuberculosis growth through increased lysosomal biogenesis and modulation of cytokine signaling. ACS Infect Dis. 2017;3(8):564–574.
  • Gotwals P, Cameron S, Cipolletta D, et al. Prospects for combining targeted and conventional cancer therapy with immunotherapy. Nat Rev Cancer. 2017;17(5):286–301.
  • Coulombe P, Meloche S. Atypical mitogen-activated protein kinases: structure, regulation and functions. Biochim Biophys Acta. 2007;1773(8):1376–1387.
  • Yang SH, Sharrocks AD, Whitmarsh AJ. Transcriptional regulation by the MAP kinase signaling cascades. Gene. 2003;320:3–21.
  • Krishna M, Narang H. The complexity of mitogen-activated protein kinases (MAPKs) made simple. Cell Mol Life Sci. 2008;65(22):3525–3544.
  • Fernandez-Medarde A, Santos E. Ras in cancer and developmental diseases. Genes Cancer. 2011;2(3):344–358.
  • Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949–954.
  • Kim G, McKee AE, Ning YM, et al. FDA approval summary: vemurafenib for treatment of unresectable or metastatic melanoma with the BRAFV600E mutation. Clin Cancer Res. 2014;20(19):4994–5000.
  • Ballantyne AD, Garnock-Jones KP. Dabrafenib: first global approval. Drugs. 2013;73(12):1367–1376.
  • Cheng Y, Tian H. Current development status of MEK inhibitors. Molecules. 2017;22:10.
  • Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10.
  • Vinay DS, Ryan EP, Pawelec G, et al. Immune evasion in cancer: mechanistic basis and therapeutic strategies. Semin Cancer Biol. 2015;35(Suppl):S185–S198.
  • Binnewies M, Roberts EW, Kersten K, et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med. 2018;24(5):541–550.
  • Maeurer MJ, Gollin SM, Martin D, et al. Tumor escape from immune recognition: lethal recurrent melanoma in a patient associated with downregulation of the peptide transporter protein TAP-1 and loss of expression of the immunodominant MART-1/Melan-A antigen. J Clin Invest. 1996;98(7):1633–1641.
  • Pasche B. Role of transforming growth factor beta in cancer. J Cell Physiol. 2001;186(2):153–168.
  • Curiel TJ, Coukos G, Zou L, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004;10(9):942–949.
  • Yang L, DeBusk LM, Fukuda K, et al. Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell. 2004;6(4):409–421.
  • Mantovani A, Sica A. Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Curr Opin Immunol. 2010;22(2):231–237.
  • Gardner A, Ruffell B. Dendritic Cells and Cancer Immunity. Trends Immunol. 2016;37(12):855–865.
  • Salmon H, Idoyaga J, Rahman A, et al. Expansion and activation of CD103(+) dendritic cell progenitors at the tumor site enhances tumor responses to therapeutic PD-L1 and BRAF inhibition. Immunity. 2016;44(4):924–938.
  • Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124(4):783–801.
  • Arthur JS, Ley SC. Mitogen-activated protein kinases in innate immunity. Nat Rev Immunol. 2013;13(9):679–692.
  • Dalod M, Chelbi R, Malissen B, et al. Dendritic cell maturation: functional specialization through signaling specificity and transcriptional programming. Embo J. 2014;33(10):1104–1116.
  • Nakahara T, Moroi Y, Uchi H, et al. Differential role of MAPK signaling in human dendritic cell maturation and Th1/Th2 engagement. J Dermatol Sci. 2006;42(1):1–11.
  • Wang S, Hong S, Yang J, et al. Optimizing immunotherapy in multiple myeloma: restoring the function of patients’ monocyte-derived dendritic cells by inhibiting p38 or activating MEK/ERK MAPK and neutralizing interleukin-6 in progenitor cells. Blood. 2006;108(13):4071–4077.
  • Lu Y, Zhang M, Wang S, et al. p38 MAPK-inhibited dendritic cells induce superior antitumour immune responses and overcome regulatory T-cell-mediated immunosuppression. Nat Commun. 2014;5:4229.
  • Wang S, Yang J, Qian J, et al. Tumor evasion of the immune system: inhibiting p38 MAPK signaling restores the function of dendritic cells in multiple myeloma. Blood. 2006;107(6):2432–2439.
  • Oosterhoff D, Lougheed S, van de Ven R, et al. Tumor-mediated inhibition of human dendritic cell differentiation and function is consistently counteracted by combined p38 MAPK and STAT3 inhibition. Oncoimmunology. 2012;1(5):649–658.
  • Dumitru CD, Ceci JD, Tsatsanis C, et al. TNF-alpha induction by LPS is regulated posttranscriptionally via a Tpl2/ERK-dependent pathway. Cell. 2000;103(7):1071–1083.
  • Kaiser F, Cook D, Papoutsopoulou S, et al. TPL-2 negatively regulates interferon-beta production in macrophages and myeloid dendritic cells. J Exp Med. 2009;206(9):1863–1871.
  • Dillon S, Agrawal A, Van Dyke T, et al. A Toll-like receptor 2 ligand stimulates Th2 responses in vivo, via induction of extracellular signal-regulated kinase mitogen-activated protein kinase and c-Fos in dendritic cells. J Immunol. 2004;172(8):4733–4743.
  • Riegel K, Schloder J, Sobczak M, et al. RAF kinases are stabilized and required for dendritic cell differentiation and function. Cell death and differentiation. 2019.
  • Smith-Garvin JE, Koretzky GA, Jordan MS. T cell activation. Annu Rev Immunol. 2009;27:591–619.
  • Cantrell D. T cell antigen receptor signal transduction pathways. Annu Rev Immunol. 1996;14:259–274.
  • DeSilva DR, Jones EA, Favata MF, et al. Inhibition of mitogen-activated protein kinase kinase blocks T cell proliferation but does not induce or prevent anergy. J Immunol. 1998;160(9):4175–4181.
  • D’Souza WN, Chang CF, Fischer AM, et al. The Erk2 MAPK regulates CD8 T cell proliferation and survival. J Immunol. 2008;181(11):7617–7629.
  • Ebert PJR, Cheung J, Yang Y, et al. MAP kinase inhibition promotes T cell and anti-tumor activity in combination with PD-L1 checkpoint blockade. Immunity. 2016;44(3):609–621.
  • Kortum RL, Rouquette-Jazdanian AK, Samelson LE. Ras and extracellular signal-regulated kinase signaling in thymocytes and T cells. Trends Immunol. 2013;34(6):259–268.
  • Schulte TW, An WG, Neckers LM. Geldanamycin-induced destabilization of Raf-1 involves the proteasome. Biochem Biophys Res Commun. 1997;239(3):655–659.
  • Grbovic OM, Basso AD, Sawai A, et al. V600E B-Raf requires the Hsp90 chaperone for stability and is degraded in response to Hsp90 inhibitors. Proc Natl Acad Sci U S A. 2006;103(1):57–62.
  • Schneider T, Martinez-Martinez A, Cubillos-Rojas M, et al. The E3 ubiquitin ligase HERC1 controls the ERK signaling pathway targeting C-RAF for degradation. Oncotarget. 2018;9(59):31531–31548.
  • Li Z, Zhou L, Prodromou C, et al. HECTD3 mediates an HSP90-dependent degradation pathway for protein kinase clients. Cell Rep. 2017;19(12):2515–2528.
  • Hong SW, Jin DH, Shin JS, et al. Ring finger protein 149 is an E3 ubiquitin ligase active on wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF). J Biol Chem. 2012;287(28):24017–24025.
  • Dogan T, Harms GS, Hekman M, et al. X-linked and cellular IAPs modulate the stability of C-RAF kinase and cell motility. Nat Cell Biol. 2008;10(12):1447–1455.
  • Noble C, Mercer K, Hussain J, et al. CRAF autophosphorylation of serine 621 is required to prevent its proteasome-mediated degradation. Mol Cell. 2008;31(6):862–872.
  • Bauerfeld C, Samavati L. Role of MEK1 in TLR4 mediated signaling. J Cell Signal. 2017;2:1.
  • Shaw AS, Kornev AP, Hu J, et al. Kinases and pseudokinases: lessons from RAF. Mol Cell Biol. 2014;34(9):1538–1546.
  • Rebocho AP, Marais R. ARAF acts as a scaffold to stabilize BRAF:CRAF heterodimers. Oncogene. 2013;32(26):3207–3212.
  • Mooz J, Oberoi-Khanuja TK, Harms GS, et al. Dimerization of the kinase ARAF promotes MAPK pathway activation and cell migration. Sci Signal. 2014;7(337):ra73.
  • Beazely MA, Alan JK, Watts VJ. Protein kinase C and epidermal growth factor stimulation of Raf1 potentiates adenylyl cyclase type 6 activation in intact cells. Mol Pharmacol. 2005;67(1):250–259.
  • Ding Q, Gros R, Gray ID, Taussig R, Ferguson SS, Feldman RD. Raf kinase activation of adenylyl cyclases: isoform-selective regulation. Mol Pharmacol. 2004;66(4):921–928.
  • Matallanas D, Birtwistle M, Romano D, et al. Raf family kinases: old dogs have learned new tricks. Genes Cancer. 2011;2(3):232–260.
  • Jette C, Thorburn A, Raf-induced A. MEK-independent signaling pathway regulates atrial natriuretic factor gene expression in cardiac muscle cells. FEBS Lett. 2000;467(1):1–6.
  • Ehrenreiter K, Piazzolla D, Velamoor V, et al. Raf-1 regulates Rho signaling and cell migration. J Cell Biol. 2005;168(6):955–964.
  • Ott PA, Henry T, Baranda SJ, et al. Inhibition of both BRAF and MEK in BRAF(V600E) mutant melanoma restores compromised dendritic cell (DC) function while having differential direct effects on DC properties. Cancer Immunol Immunother. 2013;62(4):811–822.
  • Vella LJ, Pasam A, Dimopoulos N, et al. MEK inhibition, alone or in combination with BRAF inhibition, affects multiple functions of isolated normal human lymphocytes and dendritic cells. Cancer Immunol Res. 2014;2(4):351–360.
  • Tel J, Koornstra R, de Haas N, et al. Preclinical exploration of combining plasmacytoid and myeloid dendritic cell vaccination with BRAF inhibition. J Transl Med. 2016;14:88.
  • Hajek E, Krebs F, Bent R, et al. BRAF inhibitors stimulate inflammasome activation and interleukin 1 beta production in dendritic cells. Oncotarget. 2018;9(47):28294–28308.
  • Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–2516.
  • Lee JT, Li L, Brafford PA, et al. PLX4032, a potent inhibitor of the B-Raf V600E oncogene, selectively inhibits V600E-positive melanomas. Pigment Cell Melanoma Res. 2010;23(6):820–827.
  • Sosman JA, Kim KB, Schuchter L, et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012;366(8):707–714.
  • Hauschild A, Grob JJ, Demidov LV, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(9839):358–365.
  • Poulikakos PI, Zhang C, Bollag G, et al. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature. 2010;464(7287):427–430.
  • Durrant DE, Morrison DK. Targeting the Raf kinases in human cancer: the Raf dimer dilemma. Br J Cancer. 2018;118(1):3–8.
  • Vakana E, Pratt S, Blosser W, et al. LY3009120, a panRAF inhibitor, has significant anti-tumor activity in BRAF and KRAS mutant preclinical models of colorectal cancer. Oncotarget. 2017;8(6):9251–9266.
  • Okaniwa M, Hirose M, Arita T, et al. Discovery of a selective kinase inhibitor (TAK-632) targeting pan-RAF inhibition: design, synthesis, and biological evaluation of C-7-substituted 1,3-benzothiazole derivatives. J Med Chem. 2013;56(16):6478–6494.
  • Sun Y, Alberta JA, Pilarz C, et al. A brain-penetrant RAF dimer antagonist for the noncanonical BRAF oncoprotein of pediatric low-grade astrocytomas. Neuro Oncol. 2017;19(6):774–785.
  • Pan JH, Zhou H, Zhu SB, et al. Development of small-molecule therapeutics and strategies for targeting RAF kinase in BRAF-mutant colorectal cancer. Cancer Manag Res. 2018;10:2289–2301.
  • Muller E, Bauer S, Stuhmer T, et al. Pan-Raf co-operates with PI3K-dependent signalling and critically contributes to myeloma cell survival independently of mutated RAS. Leukemia. 2017;31(4):922–933.
  • Boni A, Cogdill AP, Dang P, et al. Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lymphocyte function. Cancer Res. 2010;70(13):5213–5219.
  • Callahan MK, Masters G, Pratilas CA, et al. Paradoxical activation of T cells via augmented ERK signaling mediated by a RAF inhibitor. Cancer Immunol Res. 2014;2(1):70–79.
  • Frederick DT, Piris A, Cogdill AP, et al. BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma. Clin Cancer Res. 2013;19(5):1225–1231.
  • Reddy SM, Reuben A, Wargo JA. Influences of BRAF inhibitors on the immune microenvironment and the rationale for combined molecular and immune targeted therapy. Curr Oncol Rep. 2016;18(7):42.
  • Cooper ZA, Juneja VR, Sage PT, et al. Response to BRAF inhibition in melanoma is enhanced when combined with immune checkpoint blockade. Cancer Immunol Res. 2014;2(7):643–654.
  • Pelster MS, Amaria RN. Combined targeted therapy and immunotherapy in melanoma: a review of the impact on the tumor microenvironment and outcomes of early clinical trials. Ther Adv Med Oncol. 2019;11:1758835919830826.
  • ClinicalTrials.gov. Accesse 17 April 2020. https://clinicaltrials.gov/ct2/home.
  • Clark JI, Singh J, Ernstoff MS, et al. A multi-center phase II study of high dose interleukin-2 sequenced with vemurafenib in patients with BRAF-V600 mutation positive metastatic melanoma. J Immunother Cancer. 2018;6(1):76.
  • Mooradian MJ, Reuben A, Prieto PA, et al. A phase II study of combined therapy with a BRAF inhibitor (vemurafenib) and interleukin-2 (aldesleukin) in patients with metastatic melanoma. Oncoimmunology. 2018;7(5):e1423172.
  • Deniger DC, Kwong ML, Pasetto A, et al. A pilot trial of the combination of vemurafenib with adoptive cell therapy in patients with metastatic melanoma. Clin Cancer Res. 2017;23(2):351–362.
  • Desai J, Gan H, Barrow C, et al. Phase I, open-label, dose-escalation/dose-expansion study of lifirafenib (BGB-283), an RAF family kinase inhibitor, in patients with solid tumors. J Clin Oncol. 2020;38(19):2140–2150.;JCO1902654.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.