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Original Research

WEE1 kinase inhibition reverses G2/M cell cycle checkpoint activation to sensitize cancer cells to immunotherapy

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Article: e1488359 | Received 05 Jun 2018, Published online: 23 Jul 2018

References

  • Gajewski TF, Meng Y, Harlin H. Immune suppression in the tumor microenvironment. J Immunother. 2006;29:233–240. doi:10.1097/01.cji.0000199193.29048.56.
  • Pitt JM, Vetizou M, Daillere R, Roberti MP, Yamazaki T, Routy B, Lepage P, Boneca IG, Chamaillard M, Kroemer G, et al. Resistance mechanisms to immune-checkpoint blockade in cancer: tumor-intrinsic and -extrinsic factors. Immunity. 2016;44:1255–1269. doi:10.1016/j.immuni.2016.06.001.
  • Davis RJ, Van Waes C, Allen CT. Overcoming barriers to effective immunotherapy: mDSCs, TAMs, and Tregs as mediators of the immunosuppressive microenvironment in head and neck cancer. Oral Oncol. 2016;58:59–70. doi:10.1016/j.oraloncology.2016.05.002.
  • Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004;21:137–148. doi:10.1016/j.immuni.2004.07.017.
  • Bai XF, Liu J, Li O, Zheng P, Liu Y. Antigenic drift as a mechanism for tumor evasion of destruction by cytolytic T lymphocytes. J Clin Invest. 2003;111:1487–1496. doi:10.1172/JCI17656.
  • Leisegang M, Engels B, Schreiber K, Yew PY, Kiyotani K, Idel C, Arina A, Duraiswamy J, Weichselbaum RR, Uckert W, et al. Eradication of large solid tumors by gene therapy with a T-cell receptor targeting a single cancer-specific point mutation. Clin Cancer Res. 2016;22:2734–2743. doi:10.1158/1078-0432.CCR-15-2361.
  • Zheng P, Guo Y, Niu Q, Levy DE, Dyck JA, Lu S, Sheiman LA, Liu Y. Proto-oncogene PML controls genes devoted to MHC class I antigen presentation. Nature. 1998;396:373–376. doi:10.1038/24628.
  • Ferris RL, Whiteside TL, Ferrone S. Immune escape associated with functional defects in antigen-processing machinery in head and neck cancer. Clin Cancer Res. 2006;12:3890–3895. doi:10.1158/1078-0432.CCR-05-2750.
  • Zeligs KP, Neuman MK, Annunziata CM. Molecular pathways: the balance between cancer and the immune system challenges the therapeutic specificity of targeting nuclear factor-KappaB signaling for cancer treatment. Clin Cancer Res. 2016;22:4302–4308. doi:10.1158/1078-0432.CCR-15-1374.
  • Vitale I, Galluzzi L, Castedo M, Kroemer G. Mitotic catastrophe: a mechanism for avoiding genomic instability. Nat Rev Mol Cell Biol. 2011;12:385–392. doi:10.1038/nrm3115.
  • Allday MJ, Inman GJ, Crawford DH, Farrell PJ. DNA damage in human B cells can induce apoptosis, proceeding from G1/S when p53 is transactivation competent and G2/M when it is transactivation defective. EMBO J. 1995;14:4994–5005.
  • Toledo L, Neelsen KJ, Lukas J. Replication catastrophe: when a checkpoint fails because of exhaustion. Mol Cell. 2017;66:735–749. doi:10.1016/j.molcel.2017.05.001.
  • Hirai H, Iwasawa Y, Okada M, Arai T, Nishibata T, Kobayashi M, Kimura T, Kaneko N, Ohtani J, Yamanaka K, et al. Small-molecule inhibition of WEE1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents. Mol Cancer Ther. 2009;8:2992–3000. doi:10.1158/1535-7163.MCT-09-0463.
  • Bartek J, Lukas J. DNA damage checkpoints: from initiation to recovery or adaptation. Curr Opin Cell Biol. 2007;19:238–245. doi:10.1016/j.ceb.2007.02.009.
  • De Witt Hamer PC, Mir SE, Noske D, Van Noorden CJ, Wurdinger T. WEE1 kinase targeting combined with DNA-damaging cancer therapy catalyzes mitotic catastrophe. Clin Cancer Res. 2011;17:4200–4207. doi:10.1158/1078-0432.CCR-10-2537.
  • Eytan DF, Snow GE, Carlson S, Derakhshan A, Saleh A, Schiltz S, Cheng H, Mohan S, Cornelius S, Coupar J, et al. SMAC mimetic birinapant plus radiation eradicates human head and neck cancers with genomic amplifications of cell death genes FADD and BIRC2. Cancer Res. 2016;76:5442–5454. doi:10.1158/0008-5472.CAN-15-3317.
  • Lin Y, Choksi S, Shen HM, Yang QF, Hur GM, Kim YS, Tran JH, Nedospasov SA, Liu Z-G. Tumor necrosis factor-induced nonapoptotic cell death requires receptor-interacting protein-mediated cellular reactive oxygen species accumulation. J Biol Chem. 2004;279:10822–10828. doi:10.1074/jbc.M313141200.
  • Campana S, De Pasquale C, Carrega P, Ferlazzo G, Bonaccorsi I. Cross-dressing: an alternative mechanism for antigen presentation. Immunol Lett. 2015;168:349–354. doi:10.1016/j.imlet.2015.11.002.
  • Chen G, Shi L, Litchfield DW, Greenberg AH. Rescue from granzyme B-induced apoptosis by WEE1 kinase. J Exp Med. 1995;181:2295–2300.
  • Garimella SV, Rocca A, Lipkowitz S. WEE1 inhibition sensitizes basal breast cancer cells to TRAIL-induced apoptosis. Mol Cancer Res. 2012;10:75–85. doi:10.1158/1541-7786.MCR-11-0500.
  • Tanaka N, Patel AA, Tang L, Silver NL, Lindemann A, Takahashi H, Jaksik R, Rao X, Kalu NN, Chen T-C, et al. Replication stress leading to apoptosis within the s-phase contributes to synergism between vorinostat and AZD1775 in HNSCC harboring high-risk TP53 mutation. Clin Cancer Res. 2017;23:6541–6554. doi:10.1158/1078-0432.CCR-17-0947.
  • Hauge S, Naucke C, Hasvold G, Joel M, Rodland GE, Juzenas P, Stokke T, Syljuåsen RG. Combined inhibition of WEE1 and Chk1 gives synergistic DNA damage in S-phase due to distinct regulation of CDK activity and CDC45 loading. Oncotarget. 2017;8:10966–10979. doi:10.18632/oncotarget.14089.
  • Castedo M, Perfettini JL, Roumier T, Andreau K, Medema R, Kroemer G. Cell death by mitotic catastrophe: a molecular definition. Oncogene. 2004;23:2825–2837. doi:10.1038/sj.onc.1207528.
  • Hamilton DH, Huang B, Fernando RI, Tsang KY, Palena C. WEE1 inhibition alleviates resistance to immune attack of tumor cells undergoing epithelial-mesenchymal transition. Cancer Res. 2014;74:2510–2519. doi:10.1158/0008-5472.CAN-13-1894.
  • Osman AA, Monroe MM, Ortega Alves MV, Patel AA, Katsonis P, Fitzgerald AL, Neskey DM, Frederick MJ, Woo SH, Caulin C, et al. Wee-1 kinase inhibition overcomes cisplatin resistance associated with high-risk TP53 mutations in head and neck cancer through mitotic arrest followed by senescence. Mol Cancer Ther. 2015;14:608–619. doi:10.1158/1535-7163.MCT-14-0735-T.
  • Melnikova VO, Bolshakov SV, Walker C, Ananthaswamy HN. Genomic alterations in spontaneous and carcinogen-induced murine melanoma cell lines. Oncogene. 2004;23:2347–2356. doi:10.1038/sj.onc.1207405.
  • Onken MD, Winkler AE, Kanchi KL, Chalivendra V, Law JH, Rickert CG, Kallogjeri D, Judd NP, Dunn GP, Piccirillo JF, et al. A surprising cross-species conservation in the genomic landscape of mouse and human oral cancer identifies a transcriptional signature predicting metastatic disease. Clin Cancer Res. 2014;20:2873–2884. doi:10.1158/1078-0432.CCR-14-0205.
  • Hilburger Ryan M, Abrams SI. Characterization of CD8+ cytotoxic T lymphocyte/tumor cell interactions reflecting recognition of an endogenously expressed murine wild-type p53 determinant. Cancer Immunol Immunother. 2001;49:603–612.
  • Shah S, Caruso A, Cash H, Waes CV, Allen CT. Pools of programmed death-ligand within the oral cavity tumor microenvironment: variable alteration by targeted therapies. Head Neck. 2016;38:1176–1186. doi:10.1002/hed.24269.
  • Clavijo PE, Moore EC, Chen J, Davis RJ, Friedman J, Kim Y, Van Waes C, Chen Z, Allen CT. Resistance to CTLA-4 checkpoint inhibition reversed through selective elimination of granulocytic myeloid cells. Oncotarget. 2017;8:55804–55820. doi:10.18632/oncotarget.18437.
  • Moore E, Clavijo PE, Davis R, Cash H, Van Waes C, Kim Y, Allen C. Established T cell-inflamed tumors rejected after adaptive resistance was reversed by combination STING activation and PD-1 pathway blockade. Cancer Immunol Res. 2016. doi:10.1158/2326-6066.CIR-16-0104.
  • Davis RJ, Moore EC, Clavijo PE, Friedman J, Cash H, Chen Z, Silvin C, Van Waes C, Allen C. Anti-PD-L1 efficacy can be enhanced by inhibition of myeloid-derived suppressor cells with a selective inhibitor of PI3Kdelta/gamma. Cancer Res. 2017;77:2607–2619. doi:10.1158/0008-5472.CAN-16-2534.
  • Zhao X, Subramanian S. Intrinsic resistance of solid tumors to immune checkpoint blockade therapy. Cancer Res. 2017;77:817–822. doi:10.1158/0008-5472.CAN-16-2379.
  • Shi L, Nishioka WK, Th’ng J, Bradbury EM, Litchfield DW, Greenberg AH. Premature p34cdc2 activation required for apoptosis. Science. 1994;263:1143–1145.
  • Booher RN, Holman PS, Fattaey A. Human Myt1 is a cell cycle-regulated kinase that inhibits Cdc2 but not Cdk2 activity. J Biol Chem. 1997;272:22300–22306.
  • Parker LL, Piwnica-Worms H. Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase. Science. 1992;257:1955–1957.
  • Morgan DO. Principles of CDK regulation. Nature. 1995;374:131–134. doi:10.1038/374131a0.
  • Cuneo KC, Morgan MA, Davis MA, Parcels LA, Parcels J, Karnak D, Ryan C, Liu N, Maybaum J, Lawrence TS. WEE1 kinase inhibitor AZD1775 radiosensitizes hepatocellular carcinoma regardless of TP53 mutational status through induction of replication stress. Int J Radiat Oncol Biol Phys. 2016;95:782–790. doi:10.1016/j.ijrobp.2016.01.028.
  • Leijen S, Van Geel RM, Pavlick AC, Tibes R, Rosen L, Razak AR, Lam R, Demuth T, Rose S, Lee MA, et al. Phase I study evaluating WEE1 inhibitor AZD1775 as monotherapy and in combination with gemcitabine, cisplatin, or carboplatin in patients with advanced solid tumors. J Clin Oncol. 2016;34:4371–4380. doi:10.1200/JCO.2016.67.5991.
  • Do K, Wilsker D, Ji J, Zlott J, Freshwater T, Kinders RJ, Collins J, Chen AP, Doroshow JH, Kummar S. Phase I study of single-agent AZD1775 (MK-1775), a WEE1 kinase inhibitor, in patients with refractory solid tumors. J Clin Oncol. 2015;33:3409–3415. doi:10.1200/JCO.2014.60.4009.
  • Mendez E, Rodriguez CP, Kao M, Harbison RA, Martins RG, Futran ND, Santana-Davila R, Chow LQM. A phase I clinical trial of AZD1775 in combination with neoadjuvant weekly cisplatin and docetaxel in borderline resectable head and neck squamous cell carcinoma (HNSCC). Chicago, IL: ASCO; 2017.
  • Darzynkiewicz Z, Williamson B, Carswell EA, Old LJ. Cell cycle-specific effects of tumor necrosis factor. Cancer Res. 1984;44:83–90.
  • Baxter GT, Kuo RC, Jupp OJ, Vandenabeele P, MacEwan DJ. Tumor necrosis factor-alpha mediates both apoptotic cell death and cell proliferation in a human hematopoietic cell line dependent on mitotic activity and receptor subtype expression. J Biol Chem. 1999;274:9539–9547.
  • Fleischer B. Lysis of bystander target cells after triggering of human cytotoxic T lymphocytes. Eur J Immunol. 1986;16:1021–1024. doi:10.1002/eji.1830160826.
  • Kinkhabwala M, Sehajpal P, Skolnik E, Smith D, Sharma VK, Vlassara H, Cerami A, Suthanthiran M. A novel addition to the T cell repertory. Cell surface expression of tumor necrosis factor/cachectin by activated normal human T cells. J Exp Med. 1990;171:941–946.
  • Duke RC. Self recognition by T cells. I. Bystander killing of target cells bearing syngeneic MHC antigens. J Exp Med. 1989;170:59–71.
  • Mackay F, Loetscher H, Stueber D, Gehr G, Lesslauer W. Tumor necrosis factor alpha (TNF-alpha)-induced cell adhesion to human endothelial cells is under dominant control of one TNF receptor type, TNF-R55. J Exp Med. 1993;177:1277–1286.
  • Kojima H, Eshima K, Takayama H, Sitkovsky MV. Leukocyte function-associated antigen-1-dependent lysis of Fas+ (CD95+/Apo-1+) innocent bystanders by antigen-specific CD8+ CTL. J Immunol. 1997;159:2728–2734.
  • Schuler T, Blankenstein T. Cutting edge: CD8+ effector T cells reject tumors by direct antigen recognition but indirect action on host cells. J Immunol. 2003;170:4427–4431.
  • Fankhauser M, Broggi MAS, Potin L, Bordry N, Jeanbart L, Lund 890 AW, Da Costa E, Hauert S, Rincon-Restrepo M, Tremblay C,et al. Tumor lymphangiogenesis promotes T cell infiltration and potentiates immunotherapy in melanoma. Sci Transl Med. 2017:9: eaal4712.
  • Aranda F, Llopiz D, Diaz-Valdes N, Riezu-Boj JI, Bezunartea J, Ruiz M, Martínez M, Durantez M, Mansilla C, Prieto J, et al. Adjuvant combination and antigen targeting as a strategy to induce polyfunctional and high-avidity T-cell responses against poorly immunogenic tumors. Cancer Res. 2011;71:3214–3224. doi:10.1158/0008-5472.CAN-10-3259.
  • Spiotto MT, Rowley DA, Schreiber H. Bystander elimination of antigen loss variants in established tumors. Nat Med. 2004;10:294–298. doi:10.1038/nm999.
  • Zhang B, Karrison T, Rowley DA, Schreiber H. IFN-gamma- and TNF-dependent bystander eradication of antigen-loss variants in established mouse cancers. J Clin Invest. 2008;118:1398–1404. doi:10.1172/JCI33522.
  • Zhang D, Beresford PJ, Greenberg AH, Lieberman J. Granzymes A and B directly cleave lamins and disrupt the nuclear lamina during granule-mediated cytolysis. Proc Natl Acad Sci U S A. 2001;98:5746–5751. doi:10.1073/pnas.101329598.
  • Rao L, Perez D, White E. Lamin proteolysis facilitates nuclear events during apoptosis. J Cell Biol. 1996;135:1441–1455.
  • Judd NP, Winkler AE, Murillo-Sauca O, Brotman JJ, Law JH, Lewis JS Jr., Dunn GP, Bui JD, Sunwoo JB, Uppaluri R. ERK1/2 regulation of CD44 modulates oral cancer aggressiveness. Cancer Res. 2012;72:365–374. doi:10.1158/0008-5472.CAN-11-1831.
  • Browne KA, Blink E, Sutton VR, Froelich CJ, Jans DA, Trapani JA. Cytosolic delivery of granzyme B by bacterial toxins: evidence that endosomal disruption, in addition to transmembrane pore formation, is an important function of perforin. Mol Cell Biol. 1999;19:8604–8615.

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