Immune checkpoint in glioblastoma: Promising and challenging

Frontiers in Pharmacology

Volumn 8, Issue MAY, 2017, Pages

  Huang, Jing ^a   Liu, Fangkun ^b   Liu, Zhixiong ^b   Tang, Hui ^a   Wu, Haishan ^a   Gong, Qianni ^a   Chen, Jindong ^a  

^a CENTRAL SOUTH UNIVERSITY   (China)

^b CENTRAL SOUTH UNIVERSITY   (China)

Author keywords

Checkpoint; CTLA 4; Glioblastoma; Immunotherapy; PD 1; PD L1

Indexed keywords

ANTINEOPLASTIC AGENT; IMMUNE CHECKPOINT INHIBITOR; UNCLASSIFIED DRUG;

CANCER COMBINATION CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CANCER RADIOTHERAPY; CHEMORADIOTHERAPY; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; GASTROINTESTINAL SYMPTOM; GLIOBLASTOMA; HUMAN; KIDNEY DISEASE; METABOLIC DISORDER; NEUROLOGIC DISEASE; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RESPIRATORY TRACT DISEASE; REVIEW; SKIN DISEASE; TUMOR IMMUNITY;

EID: 85019587672     PISSN: None     EISSN: 16639812     Source Type: Journal    
DOI: 10.3389/fphar.2017.00242     Document Type: Review

References (107)

1. (2016). Immune checkpoint inhibition is effective in hypermutant Glioblastoma. Cancer Discov. 6:OF7. doi: 10.1158/2159-8290.CD-RW2016-060
2. Ansell, S. M., Lesokhin, A. M., Borrello, I., Halwani, A., Scott, E. C., Gutierrez, M., et al. (2015). PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N. Engl. J. Med. 372, 311-319. doi: 10.1056/NEJMoa1411087
3. Ardon, H., Van Gool, S. W., Verschuere, T., Maes, W., Fieuws, S., Sciot, R., et al. (2012). Integration of autologous dendritic cell-based immunotherapy in the standard of care treatment for patients with newly diagnosed glioblastoma: results of the HGG-2006 phase I/II trial. Cancer Immunol. Immunother. 61, 2033-2044. doi: 10.1007/s00262-012-1261-1
4. Asaoka, Y., Ijichi, H., and Koike, K. (2015). PD-1 blockade in tumors with mismatch-repair deficiency. N. Engl. J. Med. 373:1979. doi: 10.1056/NEJMc1510353
5. Aspelund, A., Antila, S., Proulx, S. T., Karlsen, T. V., Karaman, S., Detmar, M., et al. (2015). A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J. Exp. Med. 212, 991-999. doi: 10.1084/jem.20142290
6. Barthel, S. R., and Schatton, T. (2016). Homing in on the sweet side of immune checkpoint biology. Immunity 44, 1083-1085. doi: 10.1016/j.immuni.2016.05.003
7. Baruch, K., Deczkowska, A., Rosenzweig, N., Tsitsou-Kampeli, A., Sharif, A. M., Matcovitch-Natan, O., et al. (2016). PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease. Nat. Med. 22, 135-137. doi: 10.1038/nm.4022
8. Bhatia, S., and Thompson, J. A. (2014). Melanoma: immune checkpoint blockade story gets better. Lancet 384, 1078-1079. doi: 10.1016/S0140-6736(14)61140-5
9. Bordon, Y. (2016). Tumour immunology: a checkpoint for NK cells. Nat. Rev. Immunol. 16, 402-403. doi: 10.1038/nri.2016.68
10. Boussiotis, V. A. (2014). Somatic mutations and immunotherapy outcome with CTLA-4 blockade in melanoma. N. Engl. J. Med. 371, 2230-2232. doi: 10.1056/NEJMe1413061
11. Brahmer, J. R., and Pardoll, D. M. (2013). Immune checkpoint inhibitors: making immunotherapy a reality for the treatment of lung cancer. Cancer Immunol. Res. 1, 85-91. doi: 10.1158/2326-6066.CIR-13-0078
12. Brunet, J. F., Denizot, F., Luciani, M. F., Roux-Dosseto, M., Suzan, M., Mattei, M. G., et al. (1987). A new member of the immunoglobulin superfamily-CTLA-4. Nature 328, 267-270. doi: 10.1038/328267a0
13. Carson, M. J., Doose, J. M., Melchior, B., Schmid, C. D., and Ploix, C. C. (2006). CNS immune privilege: hiding in plain sight. Immunol. Rev. 213, 48-65. doi: 10.1111/j.1600-065X.2006.00441.x
14. Chen, L., and Flies, D. B. (2013). Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat. Rev. Immunol. 13, 227-242. doi: 10.1038/nri3405
15. Chinot, O. L., Wick, W., Mason, W., Henriksson, R., Saran, F., Nishikawa, R., et al. (2014). Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N. Engl. J. Med. 370, 709-722. doi: 10.1056/NEJMoa1308345
16. Claes, A., Idema, A. J., and Wesseling, P. (2007). Diffuse glioma growth: a guerilla war. Acta Neuropathol. 114, 443-458. doi: 10.1007/s00401-007-0293-7
17. Cserr, H. F., Harling-Berg, C. J., and Knopf, P. M. (1992). Drainage of brain extracellular fluid into blood and deep cervical lymph and its immunological significance. Brain Pathol. 2, 269-276. doi: 10.1111/j.1750-3639.1992.tb00703.x
18. Danlos, F. X., Pages, C., Roux, J., Jebali, M., Gornet, J. M., Bagot, M., et al. (2015). Atypical severe immune-related adverse effects resulting from sequenced immunotherapy in melanoma. Melanoma Res. 25, 178-179. doi: 10.1097/CMR.0000000000000132
19. De Vries, J., and Figdor, C. (2016). Immunotherapy: Cancer vaccine triggers antiviral-type defences. Nature 534, 329-331. doi: 10.1038/nature18443
20. Delconte, R. B., Kolesnik, T. B., Dagley, L. F., Rautela, J., Shi, W., Putz, E. M., et al. (2016). CIS is a potent checkpoint in NK cell-mediated tumor immunity. Nat. Immunol. 17, 816-824. doi: 10.1038/ni.3470
21. Deng, R., Cassady, K., Li, X., Yao, S., Zhang, M., Racine, J., et al. (2015). B7H1/CD80 interaction augments PD-1-dependent T cell apoptosis and ameliorates graft-versus-host disease. J. Immunol. 194, 560-574. doi: 10.4049/jimmunol.1402157
22. Derer, A., Spiljar, M., Baumler, M., Hecht, M., Fietkau, R., Frey, B., et al. (2016). Chemoradiation Increases PD-L1 Expression in Certain Melanoma and Glioblastoma Cells. Front. Immunol. 7:610. doi: 10.3389/fimmu.2016.00610
23. Ding, Z. C., Lu, X., Yu, M., Lemos, H., Huang, L., Chandler, P., et al. (2014). Immunosuppressive myeloid cells induced by chemotherapy attenuate antitumor CD4+ T-cell responses through the PD-1-PD-L1 axis. Cancer Res. 74, 3441-3453. doi: 10.1158/0008-5472.CAN-13-3596
24. Domingues, D., Turner, A., Silva, M. D., Marques, D. S., Mellidez, J. C., Wannesson, L., et al. (2014). Immunotherapy and lung cancer: current developments and novel targeted therapies. Immunotherapy 6, 1221-1235. doi: 10.2217/imt.14.82
25. Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., et al. (2002). Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat. Med. 8, 793-800. doi: 10.1038/nm0902-1039c
26. Dong, H., Zhu, G., Tamada, K., and Chen, L. (1999). B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat. Med. 5, 1365-1369. doi: 10.1038/70932
27. Dovedi, S. J., Adlard, A. L., Lipowska-Bhalla, G., McKenna, C., Jones, S., Cheadle, E. J., et al. (2014). Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 74, 5458-5468. doi: 10.1158/0008-5472.CAN-14-1258
28. Driessens, G., Kline, J., and Gajewski, T. F. (2009). Costimulatory and coinhibitory receptors in anti-tumor immunity. Immunol. Rev. 229, 126-144. doi: 10.1111/j.1600-065X.2009.00771.x
29. Durham, N. M., Nirschl, C. J., Jackson, C. M., Elias, J., Kochel, C. M., Anders, R. A., et al. (2014). Lymphocyte Activation Gene 3 (LAG-3) modulates the ability of CD4 T-cells to be suppressed in vivo. PLoS ONE 9:e109080. doi: 10.1371/journal.pone.0109080
30. Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., et al. (2009). New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer 45, 228-247. doi: 10.1016/j.ejca.2008.10.026
31. Frey, B., Rubner, Y., Wunderlich, R., Weiss, E. M., Pockley, A. G., Fietkau, R., et al. (2012). Induction of abscopal anti-tumor immunity and immunogenic tumor cell death by ionizing irradiation-implications for cancer therapies. Curr. Med. Chem. 19, 1751-1764. doi: 10.2174/092986712800099811
32. Gedeon, P. C., Riccione, K. A., Fecci, P. E., and Sampson, J. H. (2014). Antibody-based immunotherapy for malignant glioma. Semin. Oncol. 41, 496-510. doi: 10.1053/j.seminoncol.2014.06.004
33. Gibney, G. T., Kudchadkar, R. R., Deconti, R. C., Thebeau, M. S., Czupryn, M. P., Tetteh, L., et al. (2015). Safety, correlative markers, and clinical results of adjuvant nivolumab in combination with vaccine in resected high-risk metastatic melanoma. Clin. Cancer Res. 21, 712-720. doi: 10.1158/1078-0432.CCR-14-2468
34. Graeber, M. B., Scheithauer, B. W., and Kreutzberg, G. W. (2002). Microglia in brain tumors. Glia 40, 252-259. doi: 10.1002/glia.10147
35. Gryaznova, Y., Koca Caydasi, A., Malengo, G., Sourjik, V., and Pereira, G. (2016). A FRET-based study reveals site-specific regulation of spindle position checkpoint proteins at yeast centrosomes. Elife 5:e14029. doi: 10.7554/eLife.14029
36. Hamid, O., Robert, C., Daud, A., Hodi, F. S., Hwu, W. J., Kefford, R., et al. (2013). Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N. Engl. J. Med. 369, 134-144. doi: 10.1056/NEJMoa1305133
37. Harshman, L. C., Drake, C. G., and Choueiri, T. K. (2014). PD-1 blockade in renal cell carcinoma: to equilibrium and beyond. Cancer Immunol. Res. 2, 1132-1141. doi: 10.1158/2326-6066.CIR-14-0193
38. Harshyne, L. A., Hooper, K. M., Andrews, E. G., Nasca, B. J., Kenyon, L. C., Andrews, D. W., et al. (2015). Glioblastoma exosomes and IGF-1R/AS-ODN are immunogenic stimuli in a translational research immunotherapy paradigm. Cancer Immunol. Immunother. 64, 299-309. doi: 10.1007/s00262-014-1622-z
39. Hassel, J. C. (2016). Ipilimumab plus nivolumab for advanced melanoma. Lancet Oncol. 17, 1471-1472. doi: 10.1016/S1470-2045(16)30409-0
40. Hegi, M. E., Diserens, A. C., Gorlia, T., Hamou, M. F., De Tribolet, N., Weller, M., et al. (2005). MGMT gene silencing and benefit from temozolomide in glioblastoma. N. Engl. J. Med. 352, 997-1003. doi: 10.1056/NEJMoa043331
41. Heppt, M. V., Eigentler, T. K., Kähler, K. C., Herbst, R. A., Göppner, D., Gambichler, T., et al. (2016). Immune checkpoint blockade with concurrent electrochemotherapy in advanced melanoma: a retrospective multicenter analysis. Cancer Immunol. Immunother. 65, 951-959. doi: 10.1007/s00262-016-1856-z
42. Huang, R., Harmsen, S., Samii, J. M., Karabeber, H., Pitter, K. L., Holland, E. C., et al. (2016). High precision imaging of microscopic spread of glioblastoma with a targeted ultrasensitive SERRS molecular imaging probe. Theranostics 6, 1075-1084. doi: 10.7150/thno.13842
43. Hugo, W., Zaretsky, J. M., Sun, L., Song, C., Moreno, B. H., Hu-Lieskovan, S., et al. (2016). Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic Melanoma. Cell 165, 35-44. doi: 10.1016/j.cell.2016.02.065
44. Hutchinson, L. (2016). Immunotherapy: exploiting mismatch repair in GBM. Nat. Rev. Clin. Oncol. 13, 264-265. doi: 10.1038/nrclinonc.2016.56
45. Jackson, C. M., Lim, M., and Drake, C. G. (2014). Immunotherapy for brain cancer: recent progress and future promise. Clin. Cancer Res. 20, 3651-3659. doi: 10.1158/1078-0432.CCR-13-2057
46. Jacobs, J. F., Idema, A. J., Bol, K. F., Nierkens, S., Grauer, O. M., Wesseling, P., et al. (2009). Regulatory T cells and the PD-L1/PD-1 pathway mediate immune suppression in malignant human brain tumors. Neuro Oncol. 11, 394-402. doi: 10.1215/15228517-2008-104
47. Jiang, H., Hegde, S., Knolhoff, B. L., Zhu, Y., Herndon, J. M., Meyer, M. A., et al. (2016). Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat. Med. 22, 851-860. doi: 10.1038/nm.4123
48. Kataoka, K., Takeuchi, H., Mizusawa, J., Ando, M., Tsubosa, Y., Koyanagi, K., et al. (2016). A randomized Phase III trial of thoracoscopic versus open esophagectomy for thoracic esophageal cancer: Japan Clinical Oncology Group Study JCOG1409. Jpn. J. Clin. Oncol. 46, 174-177. doi: 10.1093/jjco/hyv178
49. Konstantinou, M.-P., Dutriaux, C., Gaudy-Marqueste, C., Mortier, L., Bedane, C., Girard, C., et al. (2014). Ipilimumab in melanoma patients with brain metastasis: a retro-spective multicentre evaluation of thirty-eight patients. Acta Derm. Venereol. 94, 45-49. doi: 10.2340/00015555-1654
50. Kopecky, J., Kubecek, O., Trojanova, P., Kubala, E., and Kopecky, O. (2014). [Adverse effects of modern treatment of malignant melanoma and their treatment/ management]. Klin. Onkol. 27, 393-400. doi: 10.14735/amko2014393
51. Kourie, H. R., and Klastersky, J. (2016). Immune checkpoint inhibitors side effects and management. Immunotherapy 8, 799-807. doi: 10.2217/imt-2016-0029
52. Kranz, L. M., Diken, M., Haas, H., Kreiter, S., Loquai, C., Reuter, K. C., et al. (2016). Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature 534, 396-401. doi: 10.1038/nature18300
53. Kuehn, H. S., Ouyang, W., Lo, B., Deenick, E. K., Niemela, J. E., Avery, D. T., et al. (2014). Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science 345, 1623-1627. doi: 10.1126/science.1255904
54. Kyi, C., and Postow, M. A. (2014). Checkpoint blocking antibodies in cancer immunotherapy. FEBS Lett. 588, 368-376. doi: 10.1016/j.febslet.2013.10.015
55. Lancaster, M. A., Renner, M., Martin, C. A., Wenzel, D., Bicknell, L. S., Hurles, M. E., et al. (2013). Cerebral organoids model human brain development and microcephaly. Nature 501, 373-379. doi: 10.1038/nature12517
56. Larkin, J., Hodi, F. S., and Wolchok, J. D. (2015). Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med. 373, 1270-1271. doi: 10.1056/NEJMoa1504030
57. Lesterhuis, W. J., Salmons, J., Nowak, A. K., Rozali, E. N., Khong, A., Dick, I. M., et al. (2013). Synergistic effect of CTLA-4 blockade and cancer chemotherapy in the induction of anti-tumor immunity. PLoS ONE 8:e61895. doi: 10.1371/journal.pone.0061895
58. Linsley, P. S., Greene, J. L., Brady, W., Bajorath, J., Ledbetter, J. A., and Peach, R. (1994). Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity 1, 793-801. doi: 10.1016/S1074-7613(94)80021-9
59. Liu, F., Huang, J., Ning, B., Liu, Z., Chen, S., and Zhao, W. (2016). Drug discovery via human-derived stem cell organoids. Front. Pharmacol. 7:334. doi: 10.3389/fphar.2016.00334
60. Liu, Y., and Zeng, G. (2012). Cancer and innate immune system interactions: translational potentials for cancer immunotherapy. J. Immunother. 35, 299-308. doi: 10.1097/CJI.0b013e3182518e83
61. Louveau, A., Smirnov, I., Keyes, T. J., Eccles, J. D., Rouhani, S. J., Peske, J. D., et al. (2015). Structural and functional features of central nervous system lymphatic vessels. Nature 523, 337-341. doi: 10.1038/nature14432
62. Mao, H., Lebrun, D. G., Yang, J., Zhu, V. F., and Li, M. (2012). Deregulated signaling pathways in glioblastoma multiforme: molecular mechanisms and therapeutic targets. Cancer Invest. 30, 48-56. doi: 10.3109/07357907.2011.630050
63. Melero, I., and Lasarte, J. J. (2015). Genetic basis for clinical response to CTLA-4 blockade. N. Engl. J. Med. 372:783. doi: 10.1056/NEJMc1415938
64. Michot, J. M., Bigenwald, C., Champiat, S., Collins, M., Carbonnel, F., Postel-Vinay, S., et al. (2016). Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur. J. Cancer 54, 139-148. doi: 10.1016/j.ejca.2015.11.016
65. Motzer, R. J., Rini, B. I., McDermott, D. F., Redman, B. G., Kuzel, T. M., Harrison, M. R., et al. (2015). Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. J. Clin. Oncol. 33, 1430-1437. doi: 10.1200/JCO.2014.59.0703
66. Naidoo, J., Page, D. B., and Wolchok, J. D. (2014). Immune modulation for cancer therapy. Br. J. Cancer 111, 2214-2219. doi: 10.1038/bjc.2014.348
67. Nghiem, P. T., Bhatia, S., Lipson, E. J., Kudchadkar, R. R., Miller, N. J., Annamalai, L., et al. (2016). PD-1 blockade with pembrolizumab in advanced merkel-cell carcinoma. N. Engl. J. Med. 374, 2542-2552. doi: 10.1056/NEJMoa1603702
68. Nishino, M., Sholl, L. M., Hodi, F. S., Hatabu, H., and Ramaiya, N. H. (2015). Anti-PD-1-Related Pneumonitis during Cancer Immunotherapy. N. Engl. J. Med. 373, 288-290. doi: 10.1056/NEJMc1505197
69. Ohtsuki, S., and Terasaki, T. (2007). Contribution of carrier-mediated transport systems to the blood-brain barrier as a supporting and protecting interface for the brain; importance for CNS drug discovery and development. Pharm. Res. 24, 1745-1758. doi: 10.1007/s11095-007-9374-5
70. Park, B., Yee, C., and Lee, K. M. (2014). The effect of radiation on the immune response to cancers. Int. J. Mol. Sci. 15, 927-943. doi: 10.3390/ijms15010927
71. Pegram, H. J., Andrews, D. M., Smyth, M. J., Darcy, P. K., and Kershaw, M. H. (2011). Activating and inhibitory receptors of natural killer cells. Immunol. Cell Biol. 89, 216-224. doi: 10.1038/icb.2010.78
72. Pilones, K. A., Vanpouille-Box, C., and Demaria, S. (2015). Combination of radiotherapy and immune checkpoint inhibitors. Semin. Radiat. Oncol. 25, 28-33. doi: 10.1016/j.semradonc.2014.07.004
73. Purwada, A., Jaiswal, M. K., Ahn, H., Nojima, T., Kitamura, D., Gaharwar, A. K., et al. (2015). Ex vivo engineered immune organoids for controlled germinal center reactions. Biomaterials 63, 24-34. doi: 10.1016/j.biomaterials.2015.06.002
74. Razavi, S. M., Lee, K. E., Jin, B. E., Aujla, P. S., Gholamin, S., and Li, G. (2016). Immune evasion strategies of glioblastoma. Front. Surg. 3:11. doi: 10.3389/fsurg.2016.00011
75. Reardon, D. A., Freeman, G., Wu, C., Chiocca, E. A., Wucherpfennig, K. W., Wen, P. Y., et al. (2014). Immunotherapy advances for glioblastoma. Neuro Oncol. 16, 1441-1458. doi: 10.1093/neuonc/nou212
76. Reinherz, E. L., and Schlossman, S. F. (1980). Current concepts in immunology: regulation of the immune response-inducer and suppressor T-lymphocyte subsets in human beings. N. Engl. J. Med. 303, 370-373. doi: 10.1056/NEJM198008143030704
77. Rexer, H. (2015). [Therapy of untreated local advanced or metastatic renal cell carcinoma. Phase III, randomized, open-label study of nivolumab combined with ipilimumab versus sunitinib monotherapy in subjects with previously untreated, local advanced or metastatic renal cell carcinoma (CheckMate 214-AN 36/15 of the AUO)]. Urologe A 54, 1443-1445. doi: 10.1007/s00120-015-3946-5
78. Rizvi, N. A., Mazieres, J., Planchard, D., Stinchcombe, T. E., Dy, G. K., Antonia, S. J., et al. (2015). Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 16, 257-265. doi: 10.1016/S1470-2045(15)70054-9
79. Robert, C., Long, G. V., Brady, B., Dutriaux, C., Maio, M., Mortier, L., et al. (2015). Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med. 372, 320-330. doi: 10.1056/NEJMoa1412082
80. Roopenian, D. C., and Akilesh, S. (2007). FcRn: the neonatal Fc receptor comes of age. Nat. Rev. Immunol. 7, 715-725. doi: 10.1038/nri2155
81. Rosell, R., and Karachaliou, N. (2016). Trends in immunotherapy for brain metastases. Lancet Oncol. 17, 859-860. doi: 10.1016/S1470-2045(16)30091-2
82. Roth, P., Preusser, M., and Weller, M. (2016). Immunotherapy of brain cancer. Oncol. Res. Treat. 39, 326-334. doi: 10.1159/000446338
83. Sakai, K., Shimodaira, S., Maejima, S., Udagawa, N., Sano, K., Higuchi, Y., et al. (2015). Dendritic cell-based immunotherapy targeting Wilms' tumor 1 in patients with recurrent malignant glioma. J. Neurosurg. 123, 989-997. doi: 10.3171/2015.1.JNS141554
84. Shao, R.-G., Cao, C.-X., and Pommier, Y. (2004). Abrogation of Chk1-mediated S/G2 checkpoint by UCN-01 enhances ara-C-induced cytotoxicity in human colon cancer cells. Acta Pharmacol. Sin. 25, 756-762
85. Sharon, E., Streicher, H., Goncalves, P., and Chen, H. X. (2014). Immune checkpoint inhibitors in clinical trials. Chin. J. Cancer 33, 434-444. doi: 10.5732/cjc.014.10122
86. Silk, A. W., Bassetti, M. F., West, B. T., Tsien, C. I., and Lao, C. D. (2013). Ipilimumab and radiation therapy for melanoma brain metastases. Cancer Med. 2, 899-906. doi: 10.1002/cam4.140
87. Stupp, R., Mason, W. P., Van Den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J., et al. (2005). Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 352, 987-996. doi: 10.1056/NEJMoa043330
88. Suryadevara, C. M., Verla, T., Sanchez-Perez, L., Reap, E. A., Choi, B. D., Fecci, P. E., et al. (2015). Immunotherapy for malignant glioma. Surg. Neurol. Int. 6, S68-77. doi: 10.4103/2152-7806.151341
89. Sznol, M., and Longo, D. L. (2015). Release the hounds! Activating the T-cell response to cancer. N. Engl. J. Med. 372, 374-375. doi: 10.1056/NEJMe1413488
90. Takita, M., Matsumura, T., and Kami, M. (2006). Cytokine storm and an anti-CD28 monoclonal antibody. N. Engl. J. Med. 355, 2591-2594. doi: 10.1056/NEJMc062750
91. Tang, A., Judge, T. A., Nickoloff, B. J., and Turka, L. A. (1996). Suppression of murine allergic contact dermatitis by CTLA4Ig. Tolerance induction of Th2 responses requires additional blockade of CD40-ligand. J. Immunol. 157, 117-125
92. Taube, J. M., Klein, A., Brahmer, J. R., Xu, H., Pan, X., Kim, J. H., et al. (2014). Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin. Cancer Res. 20, 5064-5074. doi: 10.1158/1078-0432.CCR-13-3271
93. Thomas, R. P., Xu, L. W., Lober, R. M., Li, G., and Nagpal, S. (2013). The incidence and significance of multiple lesions in glioblastoma. J. Neurooncol. 112, 91-97. doi: 10.1007/s11060-012-1030-1
94. Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., et al. (2012). Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366, 2443-2454. doi: 10.1056/NEJMoa1200690
95. Topalian, S. L., and Sharpe, A. H. (2014). Balance and imbalance in the immune system: life on the edge. Immunity 41, 682-684. doi: 10.1016/j.immuni.2014.11.005
96. Topalian, S. L., Sznol, M., McDermott, D. F., Kluger, H. M., Carvajal, R. D., Sharfman, W. H., et al. (2014). Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J. Clin. Oncol. 32, 1020-1030. doi: 10.1200/JCO.2013.53.0105
97. van Dam, L. S., De Zwart, V. M., and Meyer-Wentrup, F. A. (2014). The role of programmed cell death-1 (PD-1) and its ligands in pediatric cancer. Pediatr. Blood Cancer 62, 190-197. doi: 10.1002/pbc.25284
98. Vetizou, M., Pitt, J. M., Daillere, R., Lepage, P., Waldschmitt, N., Flament, C., et al. (2015). Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079-1084. doi: 10.1126/science.aad1329
99. Vlahovic, G., Fecci, P. E., Reardon, D., and Sampson, J. H. (2015). Programmed death ligand 1 (PD-L1) as an immunotherapy target in patients with glioblastoma. Neuro Oncol. 17, 1043-1045. doi: 10.1093/neuonc/nov071
100. Wainwright, D. A., Chang, A. L., Dey, M., Balyasnikova, I. V., Kim, C. K., Tobias, A., et al. (2014). Durable therapeutic efficacy utilizing combinatorial blockade against IDO, CTLA-4, and PD-L1 in mice with brain tumors. Clin. Cancer Res. 20, 5290-5301. doi: 10.1158/1078-0432.CCR-14-0514
101. Wang, C., Thudium, K. B., Han, M., Wang, X. T., Huang, H., Feingersh, D., et al. (2014). In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol. Res. 2, 846-856. doi: 10.1158/2326-6066.CIR-14-0040
102. Weller, M., Van Den Bent, M., Hopkins, K., Tonn, J. C., Stupp, R., Falini, A., et al. (2014). EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol. 15, e395-e403. doi: 10.1016/S1470-2045(14)70011-7
103. Wolchok, J. D. (2015). PD-1 Blockers. Cell 162:937. doi: 10.1016/j.cell.2015.07.045
104. Wolchok, J. D., Hoos, A., O'day, S., Weber, J. S., Hamid, O., Lebbe, C., et al. (2009). Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin. Cancer Res. 15, 7412-7420. doi: 10.1158/1078-0432.CCR-09-1624
105. Wolchok, J. D., Kluger, H., Callahan, M. K., Postow, M. A., Rizvi, N. A., Lesokhin, A. M., et al. (2013). Nivolumab plus ipilimumab in advanced melanoma. N. Engl. J. Med. 369, 122-133. doi: 10.1056/NEJMoa1302369
106. Zang, X., and Allison, J. P. (2007). The B7 family and cancer therapy: costimulation and coinhibition. Clin. Cancer Res. 13, 5271-5279. doi: 10.1158/1078-0432.CCR-07-1030
107. Zeng, J., See, A. P., Phallen, J., Jackson, C. M., Belcaid, Z., Ruzevick, J., et al. (2013). Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int. J. Radiat. Oncol. Biol. Phys. 86, 343-349. doi: 10.1016/j.ijrobp.2012.12.025