Title:Immunotherapy for Uveal Melanoma - Current Knowledge and Perspectives
Volume: 27
Issue: 8
Author(s): Snježana Kaštelan*, Antonela Gverović Antunica, Lidija Beketić Oresković, Goran Pelčić, Ema Kasun and Koraljka Hat
Affiliation:
- Department of Ophthalmology, University Hospital Dubrava, Zagreb,Croatia
Keywords:
Uveal melanoma, metastasis, immunotherapy, checkpoint inhibition, anti-CTLA-4, anti-PD-1/PD-L1.
Abstract: Uveal melanoma is the most prevalent primary intraocular tumour in adults with
the incidence between five and six cases per million people in the United States and Europe.
The prognosis of patients with uveal melanoma is unfavourable with a 5-year survival rate of
50-70% despite significant advances in local tumour treatment using radiotherapy or surgical
resection. Approximately 50% of the patients develop metastases within 15 years from initial
diagnosis, mostly in the liver. The median survival rate after the onset of metastases is 6
months. Potential treatment options for metastatic uveal melanoma are chemotherapy, targeted
therapy, and immunotherapy but no method showed satisfactory results. Immunotherapy
with checkpoint inhibition showed promising results in the treatment of cutaneous melanoma;
however, it did not appear to be equally effective with uveal melanoma. This may be
due to differences in mutational burden, expression of neoantigens between these two types of
tumour, immunosuppressive tumour microenvironment, and low immunogenicity and immune
privilege of uveal melanoma. Considering the disappointing results of treatment with
anti-CTLA-4 and PD-1/PD-L1 blockade in patients with advanced uveal melanoma several
new forms of therapies are being developed. This may include immunotherapy with
IMCgp100, glembatumumab vedotin and the infusion of autologous TILs, targeted therapy
with selective MEK inhibitors, epigenetic therapy, and nanotherapy. Better insight into the
molecular and genetic profile of uveal melanoma will facilitate detection of new prognostic
biomarkers and thus enable a better modification of the existing immunotherapy methods and
development of new forms of treatment specifically designed for uveal melanoma patients.
