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Terai et al. J Cancer Metastasis Treat 2017;3:231-43 Journal of
DOI: 10.20517/2394-4722.2017.39
Cancer Metastasis and Treatment

www.jcmtjournal.com
Topic: Cancer Immunotherapy Open Access

Immunological aspect of the liver and

metastatic uveal melanoma

Mizue Terai, Michael J. Mastrangleo, Takami Sato

Department of Medical Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Correspondence to: Dr. Mizue Terai, Department of Medical Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, 1015
Walnut Street, 1024 Curtis Building, Philadelphia, PA 19107, USA. E-mail: mizue.terai@Jefferson.edu
How to cite this article: Terai M, Mastrangleo MJ, Sato T. Immunological aspect of the liver and metastatic uveal melanoma. J Cancer Metastasis
Treat 2017;3:231-43.

ABSTRACT
Article history: Uveal (eye) melanoma is the most common primary eye malignancy in adults. Despite
Received: 1 Jun 2017 optimal treatments for primary uveal melanoma, up to 50% of patients subsequently
Accepted: 23 Oct 2017 develop systemic metastasis, often in the liver. Once hepatic metastasis develops, the
Published: 31 Oct 2017 survival of patients is generally short and currently available treatments fail to show
meaningful improvement of survival. Recent development of immune checkpoint blockades
Key words: revolutionized immunotherapy for metastatic cutaneous (skin) melanoma. Unfortunately,
Uveal melanoma, metastatic uveal melanoma is unresponsive to this approach, thus there is an unmet need
metastasis, to improve the treatment of metastatic uveal melanoma. One unique characteristic of uveal
liver, melanoma is that the majority of metastases first develop in the liver. The liver is highly
liver microenvironment, specialized in development of immune tolerance to food-derived antigens and consequently
immunotherapy
serves a unique function in the immune system. Understanding the mechanisms by which the
liver orchestrates immune-related responses is important to the development of an effective
immunotherapy for hepatic metastases such as metastatic uveal melanoma. In this review
article, the authors overview the immunological aspects of the liver and discuss approaches
to improve immunotherapy for metastatic uveal melanoma.

INTRODUCTION investigators have identified categories of patients with
a higher risk of systemic recurrence. Such risk factors
Uveal melanoma (UM) originates from the uveal tract of include: large tumor size, epithelioid cell type, extra-
the eye (iris, ciliary body, and choroid). The estimated scleral extension, loss of chromosome 3 (monosomy
[4]
incidence of UM is 5 per million in the United States, and 3), and chromosome 8q amplification . Up to 50% of
between 2 to 8 per million in Europe . Despite shared patients with UM develop metastases within 10 years
[1]
of diagnosis . UM disseminates homogeneous, as
[1]
embryologic origin, UM differs from the cutaneous there is no significant lymphatic drainage from the eye.
melanoma in biological behavior, epidemiology, The most common sites of metastasis are the liver (80-
prognostic features, and molecular profiles [2,3] . Previous 90%), then lung and bone [1,5] . Hepatic metastasis is an

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