Potentialet for forskning i immuno-onkologi

Omfanget af evidens for et immunrespons mod cancer

Både solide tumorer og hæmatologiske maligniteter er i stand til at inducere et immunrespons, som kan regulere deres initiale vækst. Denne evne er kendt som tumorimmunogenicitet.1,2

PRÆSENTATION

Traditionelt set defineres immunogene tumorer, herunder melanom og ikke-småcellet lungecancer (NSCLC), ud fra en høj forekomst af mutationer.3 Disse mutationer danner tumorantigener, som genkendes af immunsystemet, hvilket aktiverer et antitumorimmunrespons.4

 

Infiltration

Tumorinfiltrerende immunceller er til stede i tumors mikromiljø.5-17 Deres tilstedeværelse viser deres evne til at identificere og migrere til tumorceller.18

 

Elimination

Tidligt i deres udvikling kan nogle tumorer udvise tegn på spontan regression. Det tyder på, at immunsystemet er i stand til at genkende og dræbe nogle tumorceller.19

Det understøtter endvidere konceptet, at kroppens eget immunsystem har evnen til at inducere et antitumorrespons mod cancer.20 Der forskes i øjeblikket aktivt i at målrette immunsystemets signalveje til at hjælpe med at eliminere tumorceller.

Referencer

1. Bachireddy P, Burkhardt UE, Rajasagi M, Wu CJ. Hematological malignancies: at the forefront of immunotherapeutic innovation. Nat Rev Cancer. 2015;15(4):201-215. 2. Blankenstein T, Coulie Pg, Gilboa E, Jaffee EM. The determinants of tumour immunogenicity. Nat Rev Cancer. 2012;12(4):307-313. 3. Lawrence MS, Stojanov P, Polak P, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499(7457):214-218. 4. Schumacher T, Bunse L, Pusch S, et al. A vaccine targeting mutant IDH1 induced antitumor immunity. Nature. 2014;512(7514):324-327. 5. Ansell SM, Stenson M, Habermann TM, Jelinek DF, Witzig TE. CD41 T-Cell Immune Response to Large B-Cell Non-Hodgkin’s Lymphoma Predicts Patient Outcome. J Clin Oncol. 2001;19(3):720-726. 6. Berghoff AS, Kiesel B, Widhalm G, et al. Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma. Neuro Oncol. 2015;17(8):1064-1075. 7. Dhodapkar MV, Krasovsky J, Olson K. T cells from the tumor microenvironment of patients with progressive myeloma can generate strong, tumor-specific cytolytic responses to autologous, tumor-loaded dendritic cells. Proc Natl Acad Sci USA. 2002;99(20):13009-13013. 8. Gentles AJ, Newman AM, Liu CL, et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med. 2015;21(8):938-945. 9. Heusinkveld M, Goedemans R, Briet RJP, et al. Systemic and local human papillomavirus 16-specific T-cell immunity in patients with head and neck cancer. Int J Cancer. 2012;131(2):E74-E85. 10. Hussein MR, AL-Assiori Mana, Musalan AO. Phenotypic characterization of the infiltrating immune cells in normal prostate, benign nodular prostatic hyperplasia and prostatic adenocarcinoma. Exp Mol Pathol. 2009;86(2):108-113. 11. Itsumi M, Tatsugami K. Immunotherapy for Renal Cell Carcinoma. Clin Dev Immunol. 2010; 2010;284581. doi:10.1155/2010/284581. 12. Kandalaft LE, Motz GT, Duraiswamy J, Coukos G. Tumor immune surveillance and ovarian cancer: lessons in immune mediated tumor rejection or tolerance. Cancer Metastasis Rev. 2011;30:141-151. 13. Liang J, Ding T, Guo Z-W, et al. Expression pattern of tumour-associated antigens in hepatocellular carcinoma: association with immune infiltration and disease progression. Br J Cancer. 2013;109(4):1031-1039. 14. Schreck S, Friebel D, Buettner M, et al. Prognostic impact of tumour-infiltrating Th2 and regulatory T cells in classical Hodgkin lymphoma. Hematol Oncol. 2009;27(1):31-39. 15. Sharma P, Shen Y, Wen S, et al. CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma. Proc Natl Acad Sci USA. 2007;104(10):3967-3972. 16. Tran E, Ahmadzadeh M, Lu Y-C, et al. Immunogenicity of somatic mutations in human gastrointestinal cancers. Science. 2015;350(6266):1387-1390. 17. Whitford P, Mallon EA, George WD, Campbell AM. Flow cytometric analysis of tumour infiltrating lymphocytes in breast cancer. Br J Cancer. 1990;62(6):971-975. 18. Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013;14(10):1014-1022. 19. Kalialis LV, Drzewiecki KT, Klyvner H. Spontaneous regression of metastases from melanoma: review of the literature. Melanoma Res. 2009;19(5):275-282. 20. Maio M. Melanoma as a model tumour for Immuno-Oncology. Ann Oncol. 2012;23(suppl 8):viii10-viii14.