Circulating immune profile can predict survival of metastatic uveal melanoma patients: results of an exploratory study

ABSTRACT

Metastatic uveal melanoma (UM) is a poor prognosis malignancy. Immunotherapy is commonly employed, despite the low activity, considering the lack of other effective systemic treatments. In this study, the prognostic and predictive role of soluble immune checkpoints and inflammatory cytokines/chemokines in 22 metastatic UM patients was evaluated. Baseline levels of these molecules were assessed, as well as their changes during anti-PD-1 therapy. The correlation between soluble immune checkpoints/cytokines/chemokines and survival was analyzed. A comparison between circulating immune profile of metastatic cutaneous melanoma (CM), for which immunotherapy is a mainstay of treatment, and UM during anti-PD-1 therapy was also performed. Three immune molecules resulted significantly higher in metastatic UM patients with survival <6 months versus patients with survival ≥6 months: IL-8, HVEM and IDO activity. Considering these three molecules, we obtained a baseline score able to predict patients’ survival. The same three molecules, together with soluble(s) CD137, sGITR and sCD27, resulted significantly lower in patients with survival >30 months. We also observed an increase of sCD137, sCD28, sPD-1, sPD-L2 sLAG3, sCD80 and sTim3 during anti-PD-1 treatment, as well as IDO activity, IP-10 and CCL2. Several of these molecules were significantly higher in UM compared to CM patients during anti-PD-1 therapy. The analysis of circulating immune molecules allows to identify patients with poor prognosis despite immunotherapy and patients with long survival treated with an anti-PD-1 agent. The different serum concentration of these molecules during anti-PD-1 therapy between UM and CM reflects the different efficacy of immune checkpoint inhibitors.

KEYWORDS:

• Uveal melanoma
• PD-1
• soluble checkpoint
• immunotherapy

Acknowledgments

EB is currently supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) under In-vestigator Grant (IG) No. IG20583 and by Institutional funds of Università Cattolica del Sacro Cuore (UCSC-project D1-2018/2019). GT is supported by AIRC, IG18599, AIRC 5 × 1000 21052. GS is currently supported by Institutional funds of Università Cattolica del Sacro Cuore (UCSC-project D1 2018/2019). MN reports research grant from Incyte and IPSEN.

Disclosure statement

The authors declare that they have no competing interests. ER had a role as consultant for MSD and Novartis. EB reported speakers’ and travel fees from MSD, Astra-Zeneca, Celgene, Pfizer, Hel-sinn, Eli-Lilly, BMS, Novartis, and Roche; consultant’s fees from Roche and Pfizer; and institution-al research grants from AstraZeneca and Roche. PM has/had a role as consultant/advisory for BMS, Roche Genentech, MSD, Novartis, Amgen, Merk Serono, Pierre Fabre and Incyte. GT has a role as consultant for BMS and MSD.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2022.2034377.

Additional information

Funding

The study was funded by institutional resources by Università Cattolica del Sacro Cuore.