Name

Le récepteur immunorégulateur V-Set : un gène immunosuppresseur qui prédit le pronostic des patients atteints du mélanome uvéal malin primaire

Uveal melanoma is the most common primary intraocular cancer in adults. It is known by its high metastasis potential making it one of the most aggressive and lethal cancers. Recently, immune checkpoints such as programmed cell death protein-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) provided a lot of hope by increasing significatively patients’ survival in multiple human cancers; especially in cutaneous melanoma. However, patients with uveal melanoma are excluded from these studies because of their molecular characteristics that tend to be widely different from cutaneous melanoma. Likewise, a better understanding of immune checkpoints roles in uveal melanoma remains important. This study aims to analyze the expression of V-Set Immunoregulatory Receptor (VSIR) as a novel immune checkpoint, to correlate it with PD-1 and CTLA-4 expression and to evaluate its prognostic value in 2 populations with primary malignant uveal melanoma. 

Evaluation of VSIR, CTLA-4 and PD-1 expression was performed through TCGA database analysis and immunohistochemistry on 2 different cohorts of patients with malignant uveal melanoma.

RNA sequencing of 80 patients from the TCGA cohort shows that VSIR is significantly related to advanced stage and the most aggressive histological type in uveal melanoma. To further confirm our results, proteomic analysis revealed that VSIR is expressed in the majority of cases and was associated with tumor aggressiveness consistency with our transcriptomic results. Surprisingly, PD-1 expression was negative in all patients, whereas CTLA-4 expression was high in advanced stage patients compared to primary uveal melanoma patients. 

The expression profile of VSIR, PD-1 and CTLA-4 was found to vary among tumors. Different studies assessed their prognosis value in multiple types of cancers such as cutaneous melanoma, lung cancer and breast cancer (1-3). Therefore, our study suggests that VSIR and CTLA-4 genes may be involved in uveal melanoma progression and its invasion. However, the low expression of PD-1 may explain the non-effectiveness of anti-PD-1 therapies tested till now in the treatment of UM patients confirming that in this type of tumor, it may be less effective (4).

Here we suggest that VSIR gene is involved in uveal melanoma progression and its invasion. It may be may be therefore one of the promising immune checkpoints. Taking together, exploring its expression profile may predict response to immunotherapy and my lead to the improvement of precision therapy in malignant uveal melanoma patients.