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Terai et al. The liver and metastatic uveal melanoma
the antibody releases MMAE, a potent cytotoxic Conflicts of interest
agent. gpNMB is overexpressed by multiple tumors There are no conflicts of interest.
including melanoma and breast cancer. Eighteen of 21
primary UM tissue specimens (85.7%) evaluated by Patient consent
immunohistochemical analysis (IHC) expressed gpNMB Not applicable.
in 10-90% of tumor cells with variable intensity [71] . A
phase 2 clinical study for Glembatumumab vedotin in Ethics approval
metastatic or locally recurrent UM (NCT02363283) Not applicable.
has been recently concluded [72] . The final results are
awaited. REFERENCES
CONCLUSION 1. Kaliki S, Shields CL, Shields JA. Uveal melanoma: estimating
prognosis. Indian J Ophthalmol 2015;63:93-102.
2. Collaborative Ocular Melanoma Study Group. Assessment of
There is no standard care for the treatment of patients metastatic disease status at death in 435 patients with large choroidal
with metastatic UM. The effectiveness of treatments for melanoma in the Collaborative Ocular Melanoma Study (COMS):
metastatic UM seems to be very limited, and induction of COMS report no. 15. Arch Ophthalmol 2001;119:670-6.
immunity against UM cells may be the major challenge. 3. Ewens KG, Kanetsky PA, Richards-Yutz J, Purrazzella J, Shields CL,
We are just beginning to understand the immune Ganguly T, Ganguly A. Chromosome 3 status combined with BAP1
and EIF1AX mutation profiles are associated with metastasis in uveal
suppressive pathways involved in metastatic UM and melanoma. Invest Ophthalmol Vis Sci 2014;55:5160-7.
their tumor microenvironment. As we described in this 4. Damato B, Eleuteri A, Taktak AF, Coupland SE. Estimating prognosis
review article, immune reactions can be generated for survival after treatment of choroidal melanoma. Prog Retin Eye Res
against cancer cells under specific circumstances such 2011;30:285-95.
as the presence of cognitive antigens, an increasing 5. Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in
level of APCs, high affinity of interactive TCR, and 6. incidence, treatment, and survival. Ophthalmology 2011;118:1881-5.
Malina HZ, Martin XD. Indoleamine 2,3-dioxygenase: antioxidant
depletion of inhibitory immune cells or molecules in enzyme in the human eye. Graefes Arch Clin Exp Ophthalmol
the liver. Considering potential pre-existing immune 1996;234:457-62.
tolerance against UM cells, low mutational burden, and 7. Bronkhorst IH, Vu TH, Jordanova ES, Luyten GP, Burg SH, Jager
an immune-modulating microenvironment in the liver, MJ. Different subsets of tumor-infiltrating lymphocytes correlate
mechanical perturbation of hepatic metastasis with with macrophage influx and monosomy 3 in uveal melanoma. Invest
or followed by immunostimulatory molecules would 8. Ophthalmol Vis Sci 2012;53:5370-8.
Bronkhorst IH, Ly LV, Jordanova ES, Vrolijk J, Versluis M, Luyten
be a reasonable approach. Alternatively, the usage of GP, Jager MJ. Detection of M2-macrophages in uveal melanoma and
ex-vivo activated tumor-specific T cells or mimicking relation with survival. Invest Ophthalmol Vis Sci 2011;52:643-50.
approaches such as bispecific fusion proteins would 9. Makitie T, Summanen P, Tarkkanen A, Kivela T. Tumor-infiltrating
be a promising approach against metastatic UM as macrophages (CD68(+) cells) and prognosis in malignant uveal
melanoma. Invest Ophthalmol Vis Sci 2001;42:1414-21.
suggested by on-going clinical trials. Inhibitors of key 10. Mougiakakos D, Johansson CC, Trocme E, All-Ericsson C, Economou
signal pathways unique to metastatic UM might also be MA, Larsson O, Seregard S, Kiessling R. Intratumoral forkhead box
helpful in increasing immunogenicity of UM cells, which P3-positive regulatory T cells predict poor survival in cyclooxygenase-
in turn might improve the efficacy of currently available 2-positive uveal melanoma. Cancer 2010;116:2224-33.
immune checkpoint blockades. Further collaboration 11. Vetter CS, Lieb W, Brocker EB, Becker JC. Loss of nonclassical
between basic immunology researchers and clinical MHC molecules MIC-A/B expression during progression of uveal
melanoma. Br J Cancer 2004;91:1495-9.
scientists is required for the development of more 12. Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C, Flavell RA.
effective immunotherapy strategies against metastatic Inflammation-induced cancer: crosstalk between tumours, immune
UM. cells and microorganisms. Nat Rev Cancer 2013;13:759-71.
13. Vidal-Vanaclocha F. The prometastatic microenvironment of the liver.
DECLARATIONS Cancer Microenviron 2008;1:113-29.
14. Bakalian S, Marshall JC, Logan P, Faingold D, Maloney S, Di Cesare
S, Martins C, Fernandes BF, Burnier MN Jr. Molecular pathways
Authors’ contributions mediating liver metastasis in patients with uveal melanoma. Clin
Drafting and writing the manuscript: M. Terai Cancer Res 2008;14:951-6.
Manuscript’s conception, revision and supervised: 15. van den Bosch T, Koopmans AE, Vaarwater J, van den Berg M, de
M.J. Mastrangleo, T. Sato Klein A, Verdijk RM. Chemokine receptor CCR7 expression predicts
poor outcome in uveal melanoma and relates to liver metastasis
whereas expression of CXCR4 is not of clinical relevance. Invest
Financial support and sponsorship Ophthalmol Vis Sci 2013;54:7354-61.
None. 16. Li H, Alizadeh H, Niederkorn JY. Differential expression of chemokine
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