DISCOVERIES (ISSN 2359-7232), 2019, April-June issue

CITATION: 

Submitted: June 5th, 2019; Revised: June 24th, 2019; Accepted: June 25th, 2019; Published: June 26th, 2019; 

 GO BACK to 2019, April-June issue

 GO BACK to DISCOVERIES

Immunotherapy for Melanoma Brain Metastases

Gil Nuno Castro Fernandes *

Comenius University, Faculty of Medicine, Bratislava, Slovakia;

*Corresponding authors: Gil Nuno Castro Fernandes, MS, Comenius University, Sasinkova 4, 813 72 Bratislava, Slovakia; Email: gilcastrofernandes@hotmail.com

Abstract

Brain metastases are about ten times more frequent than a brain primary tumor, being present in 20-40% of adults with systemic cancer. Together with lung cancer and breast cancer, skin cancers such as melanoma are top primary tumors which metastasizes to the brain. Advanced melanoma is well known for its propensity to metastasize to the brain, with 80% of patients presenting brain metastasis at the autopsy. However, current therapies are not very efficient and brain metastases are in most of the cases lethal. Treatment of melanoma brain metastases with surgery and/or radiation therapy results in a median overall survival of only about four months after diagnosis. New immunotherapies such as targeted or immunomodulatory drugs, many in clinical trials, have shown promise, with some immunomodulatory drugs being able to at least double the overall survival rates for patients with melanoma brain metastases. This review focuses on the recent advances and future potential of using immunotherapy, such as the newly developed immunomodulatory drugs, for melanoma brain metastases therapy. Immunomodulatory drugs bring a great promise as new tools for melanoma treatment in particular and for the treatment of other types of malignancies in general.

Access full text of the manuscript here: Full text (pdf)

References

1. Langley RR, Fidler IJ. The biology of brain metastasis. Clin Chem. 2013 Jan;59(1):180-9. doi: 10.1373/clinchem.2012.193342.
2. Patchell RA. The management of brain metastases. Cancer Treat Rev. 2003 Dec;29(6):533-40.
3. Johnson JD, Young B. Demographics of brain metastasis. Neurosurg Clin N Am. 1996 Jul;7(3):337-44.
4. Lassman AB, DeAngelis LM. Brain metastases. Neurol Clin. 2003 Feb;21(1):1-23, vii.
5. Farber SH, Tsvankin V, Narloch JL, Kim GJ, Salama AK, Vlahovic G, Blackwell KL, Kirkpatrick JP, Fecci PE. Embracing rejection: Immunologic trends in brain metastasis. Oncoimmunology. 2016 Apr 11;5(7):e1172153.
6. Cruz-Muñoz W, Kerbel RS. Preclinical approaches to study the biology and treatment of brain metastases. Semin Cancer Biol. 2011 Apr;21(2):123-30.
7. Jindal V, Gupta S. Expected Paradigm Shift in Brain Metastases Therapy-Immune Checkpoint Inhibitors. Mol Neurobiol. 2018 Aug;55(8):7072-7078.
8. Iorgulescu JB, Harary M, Zogg CK, Ligon KL, Reardon DA, Hodi FS et al. Improved Risk-Adjusted Survival for Melanoma Brain Metastases in the Era of Checkpoint Blockade Immunotherapies: Results from a National Cohort. Cancer Immunol Res. 2018 Sep;6(9):1039-1045.
9. American Cancer Society. What is Cancer Immunotherapy. Accessed in June 2019: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/what-is-immunotherapy.html
10. Soare GR, Soare CA. Immunotherapy for Breast Cancer:  First FDA Approved Regimen. Discoveries 2019, 7(1); e91. DOI:10.15190/d.2019.4.
11. Chang L, Chang M, Chang HM, Chang F. Microsatellite Instability: A Predictive Biomarker for Cancer Immunotherapy. Appl Immunohistochem Mol Morphol. 2018 Feb;26(2):e15-e21.
12. Puhalla S, Elmquist W, Freyer D, Kleinberg L, Adkins C, Lockman P et al. Unsanctifying the sanctuary: challenges and opportunities with brain metastases. Neuro Oncol. 2015 May;17(5):639-51.
13. Davies MA, Liu P, McIntyre S, Kim KB, Papadopoulos N, Hwu WJ et al. Prognostic factors for survival in melanoma patients with brain metastases. Cancer. 2011 Apr 15;117(8):1687-96.
14. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013 Nov;19(11):1423-37.
15. Chen Q, Boire A, Jin X, Valiente M, Er EE, Lopez-Soto A et al. Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer. Nature. 2016 May 26;533(7604):493-498.
16. Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, Detmar M et al. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med. 2015 Jun 29;212(7):991-9.
17. Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015 Jul 16;523(7560):337-41.
18. Louveau A, Harris TH, Kipnis J. Revisiting the Mechanisms of CNS Immune Privilege. Trends Immunol. 2015 Oct;36(10):569-577.
19. Weiss N, Miller F, Cazaubon S, Couraud PO. The blood-brain barrier in brain homeostasis and neurological diseases. Biochim Biophys Acta. 2009 Apr;1788(4):842-57.
20. Berghoff AS, Fuchs E, Ricken G, Mlecnik B, Bindea G, Spanberger T et al. Density of tumor-infiltrating lymphocytes correlates with extent of brain edema and overall survival time in patients with brain metastases. Oncoimmunology. 2015 Jun 9;5(1):e1057388.
21. Quail DF, Joyce JA. The Microenvironmental Landscape of Brain Tumors. Cancer Cell. 2017 Mar 13;31(3):326-341.
22. Osswald M, Jung E, Sahm F, Solecki G, Venkataramani V, Blaes J et al. Brain tumour cells interconnect to a functional and resistant network. Nature. 2015 Dec 3;528(7580):93-8.
23. Lin X, DeAngelis LM. Treatment of Brain Metastases. J Clin Oncol. 2015 Oct 20;33(30):3475-84.
24. Staudt M, Lasithiotakis K, Leiter U, Meier F, Eigentler T, Bamberg M et al. Determinants of survival in patients with brain metastases from cutaneous melanoma. Br J Cancer. 2010 Apr 13;102(8):1213-8.
25. Cohen JV, Kluger HM. Systemic Immunotherapy for the Treatment of Brain Metastases. Front Oncol. 2016 Mar 9;6:49.
26. Hottinger AF, Pacheco P, Stupp R. Tumor treating fields: a novel treatment modality and its use in brain tumors. Neuro Oncol. 2016 Oct;18(10):1338-49.
27. Owyong M, Hosseini-Nassab N, Efe G, Honkala A, van den Bijgaart RJE, Plaks V et al. Cancer Immunotherapy Getting Brainy: Visualizing the Distinctive CNS Metastatic Niche to Illuminate Therapeutic Resistance. Drug Resist Updat. 2017 Nov;33-35:23-35.
28. Nowak-Sadzikowska J, Walasek T, Jakubowicz J, Blecharz P, Reinfuss M. Current treatment options of brain metastases and outcomes in patients with malignant melanoma. Rep Pract Oncol Radiother. 2016 May-Jun;21(3):271-7.
29. Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014 Apr;15(4):387-95..
30. Glitza Oliva I, Tawbi H, Davies MA. Melanoma Brain Metastases: Current Areas of Investigation and Future Directions. Cancer J. 2017 Jan/Feb;23(1):68-74.
31. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011 Jun 30;364(26):2507-16.
32. Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012 Jul 28;380(9839):358-65.
33. Aim at Melanoma Foundation. FDA Approved Drugs. Accessed in June 2019: https://www.aimatmelanoma.org/melanoma-treatment-options/fda-approved-drugs-for-melanoma/
34. Cancer Research Institute, Jedd D. Wolchok. Immunotherapy for Melanoma: How is Immunotherapy Changing the Outlook for Patients with Melanoma? Accessed in June 2019: https://www.cancerresearch.org/immunotherapy/cancer-types/melanoma
35. Chen G, Davies MA. Emerging insights into the molecular biology of brain metastases. Biochem Pharmacol. 2012 Feb 1;83(3):305-14.
36. McQuade J, Davies MA.Converting biology into clinical benefit: lessons learned from BRAF inhibitors. Melanoma Manag. 2015;2(3):241-254.
37. Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012 Mar 8;366(10):925-31.
38. Kamath SD, Kumthekar PU. Immune Checkpoint Inhibitors for the Treatment of Central Nervous System (CNS) Metastatic Disease. Front Oncol. 2018 Sep 27;8:414.
39. Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993.J Clin Oncol. 1999 Jul;17(7):2105-16.
40. Brigham and Women's Hospital. Immunotherapy doubles survival rates for patients with melanoma brain metastases. Accessed in June 2019: https://medicalxpress.com/news/2018-07-immunotherapy-survival-patients-melanoma-brain.html
41. Shevach EM. Biological functions of regulatory T cells. Adv Immunol. 2011;112:137-76.
42. Francisco LM, Sage PT, Sharpe AH. The PD-1 pathway in tolerance and autoimmunity. Immunol Rev. 2010 Jul;236:219-42.
43. Knisely JP, Yu JB, Flanigan J, Sznol M, Kluger HM, Chiang VL. Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival. J Neurosurg. 2012 Aug;117(2):227-33.