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to activate the “type 1” inflammatory response can be   Award to NIH R01CA125244 (Soto H), a UCLA Scholars in
           implemented.  Enhancing  the  endogenous immune    Translational Medicine Program Award (Yang I), and the
           response by deactivating the ensuing chronic       STOP CANCER Jason Dessel Memorial Seed Grant (Yang I).
           inflammatory tumor microenvironment might provoke
           an immune response potent enough to activate and   REFERENCES
           mobilize endogenous CTL and NK cells to eliminate
           the threat posed by high-grade cancerous masses.   1.   Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y,
                                                                  Stroup NE, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical
                                                                  report: Primary brain and central nervous system tumors
           CONCLUSION                                             diagnosed in the United States in 2006-2010.  Neuro Oncol
                                                                  2013;15 Suppl 2:ii1-56.
           It has long been held that tumor cells outwit the   2.   Stupp  R,  Mason  WP,  van  den  Bent  MJ,  Weller  M,  Fisher  B,
           host’s defenses by altering their own cellular signaling   Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U,
                                                                  Curschmann  J, Janzer  RC, Ludwin  SK, Gorlia  T, Allgeier  A,
           pathways. The pathway exploited to achieve malignancy   Lacombe  D, Cairncross  JG, Eisenhauer  E, Mirimanoff RO;
           may be a combination of unique derivations. Gliomas    European Organisation for Research and Treatment of Cancer
           are known to exhibit compensatory activity in that     Brain Tumor and Radiotherapy Groups; National Cancer Institute
           when supplied with selective pressure from one         of Canada Clinical Trials Group. Radiotherapy plus concomitant
                                                                  and adjuvant temozolomide for glioblastoma.  N  Engl J Med
           treatment, they readily adapt with other mutations to   2005;352:987-96.
           survive. Other mounting evidence now suggests that   3.   Hansson GK. Inflammation, atherosclerosis, and coronary artery
           some of the pathways exploited by cancer cells adopt a   disease. N Engl J Med 2005;352:1685-95.
           more malignant phenotype and are simply responses to   4.   Lindsberg PJ, Grau AJ. Inflammation and infections as risk factors
                                                                  for ischemic stroke. Stroke 2003;34:2518-32.
           the stimuli created by the rapidly dividing tumor cells   5.   Sartor  RB.  Mechanisms of disease: pathogenesis of Crohn’s
           rather than novel re-circuited pathways exploited by   disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol
           neoplastic cells for growth. One of the crucial responses   2006;3:390-407.
           facilitating and nurturing cancerous transformation   6.   McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid
                                                                  arthritis. Nat Rev Immunol 2007;7:429-42.
           is inflammation. A chronically active inflammatory   7.   Peterson JW, Bo L, Mork S, Chang A, Trapp BD. Transected neurites,
           microenvironment provides the developing cancerous     apoptotic neurons, and reduced inflammation in cortical multiple
           mass with proliferative  and  mutational  factors      sclerosis lesions. Ann Neurol 2001;50:389-400.
           necessary to realize “self-sufficiency”. It is evident that   8.   Bousquet J, Chanez P, Lacoste JY, Barnéon G, Ghavanian N,
                                                                  Enander I, Venge P, Ahlstedt S, Simony-Lafontaine J, Godard P,
           some tumors can bypass this “nurturing stage” as might   Michel FB. Eosinophilic inflammation in asthma. N Engl J Med
           be expected with primary GBM. Regardless, once this    1990;323:1033-9.
           “self-sufficiency” is realized, the tumor is able to survive   9.   Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM,
           outside of the cancer stem cell niche. Empowered with   Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE,
                                                                  Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L,
           constant proliferative cues the tumor mass divides     Mrak  R, Mackenzie  IR, McGeer  PL, O’Banion  MK, Pachter  J,
           uncontrolled. The increased proliferation results in   Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W,
           necrosis and the resultant environment is skewed more   Strohmeyer R, Tooyoma I, Van Muiswinkel FL, Veerhuis R, Walker D,
           strongly towards the Th2 inflammatory response. Thus,   Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T. Inflammation
                                                                  and alzheimer’s disease. Neurobiol Aging 2000;21:383-421.
           for high-grade gliomas a higher Th2/Th1 cytokine ratio   10.  Dantzer R. Depression and inflammation: an intricate relationship.
           supports the production of other immunosuppressive     Biol Psychiatry 2012;71:4-5.
           factors. To mount a successful cytotoxic anti-tumor   11.  Schubert C, Hong S, Natarajan L, Mills PJ, Dimsdale JE. The
           response, it is crucial to restore a balanced Th2/Th1   association between fatigue and inflammatory marker levels
                                                                  in cancer patients: a quantitative review.  Brain Behav Immun
           cytokine ratio of 1:1 or less. This should decrease the   2007;21:413-27.
           proliferative rate of the tumor mass as well, since it   12.  Moalem G, Tracey DJ. Immune and inflammatory mechanisms in
           is the Th2 response that ultimately works with the     neuropathic pain. Brain Res Rev 2006;51:240-64.
           tumor cell to drive the angiogenic response. Ultimately,   13.  Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow?
                                                                  Lancet 2001;357:539-45.
           successful brain tumor immunotherapy should leave   14.  Mantovani  A, Allavena  P, Sica  A, Balkwill  F. Cancer-related
           patients with intact immunosurveillance function and   inflammation. Nature 2008;454:436-44.
           the ability to enact a cell-mediated response in the   15.  Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD,
           event of recurrence.                                   Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M,
                                                                  O’Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S,
                                                                  Jakkula  L, Feiler  HS, Hodgson  JG, James  CD, Sarkaria  JN,
           ACKNOWLEDGMENTS                                        Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW,
                                                                  Meyerson M, Getz G, Perou CM, Hayes DN; Cancer Genome Atlas
           Supported in part by NIH R01CA125244 (Kruse CA,        Research Network. Integrated genomic analysis identifies clinically
           Liau LM), R01CA154256 (Kruse CA), R01 CA121258         relevant subtypes of glioblastoma characterized by abnormalities in
                                                                  PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010;17:98-110.
           (Kasahara N,  Kruse  CA),  the  Joan  S.  Holmes Memorial   16.  Philip  M, Rowley  DA, Schreiber  H. Inflammation as a tumor
           Research Fund (Kruse CA), NIH/NCATS UCLA CTSI Grant    promoter in cancer induction. Semin Cancer Biol 2004;14:433-9.
           Number UL1TR000124 (Liau LM), a NIH Minority Supplement   17.  Wager-Smith  K, Markou  A. Depression: A  repair response to



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