Abstract
BackgroundNumerous studies indicated that tumor-infiltrated immune cells (TIC) in the microenvironment are substantially linked to immunotherapy response and cancer prognosis. However, systematic studies of infiltrated immune cell characterization in uveal melanoma (UM) for prognosis and immune checkpoint blockade therapy are lacking.MethodsUM datasets were extracted from open access resources (TCGA and GEO databases). The tumor-infiltrated immune cells in the microenvironment were decoded by using the CIBERSORT algorithm, which was further applied to classify UM patients into subgroups using an unsupervised clustering method. The Boruta algorithm and principal component analysis were used to calculate the TIC scores for UM patients. Kaplan–Meier curves were plotted to prove the prognostic value of TIC scores. Besides, the correlations of the TIC score with clinical features, mutated characteristics, and the immune therapeutic response were subsequently investigated.ResultsAs a result, we defined three subtypes among 171 UM patients according to the TIC profiles and then calculated the TIC score to characterize the immune patterns for all patients. We discovered that high-TIC score patients with low BAP1 and high EIF1AX mutations have a better prognosis than low-TIC score patients. Activation of immune inflammatory response and increase in immune checkpoint-related genes in high-TIC score patients may account for good prognosis and immunotherapy response. Three melanoma cohorts received immunotherapy, proving that high-TIC score patients have substantial clinical and immune therapeutic improvements. Besides, several potential therapeutic agents were identified in the low-TIC score group.ConclusionOur study afforded a comprehensive view of infiltrated immune cell characterization to elucidate different immune patterns of UM. We also established a robust TIC-score signature, which may work as a prognostic biomarker and immune therapeutic predictor.
Highlights
Numerous studies indicated that tumor-infiltrated immune cells (TIC) in the microenvironment are substantially linked to immunotherapy response and cancer prognosis
Immune checkpoint inhibitors like anti-PD1, anti-PDL1, and antiCTLA4 have been effectively employed in metastatic cutaneous melanoma, one of the biggest drawbacks for application of immunotherapy in uveal melanoma (UM) is that only approximately 0% to 6% of response rate was observed in clinical use [6–8]
A total of 171 uveal melanoma (UM) samples were pooled into a big cohort that was studied in this research
Summary
Numerous studies indicated that tumor-infiltrated immune cells (TIC) in the microenvironment are substantially linked to immunotherapy response and cancer prognosis. Systematic studies of infiltrated immune cell characterization in uveal melanoma (UM) for prognosis and immune checkpoint blockade therapy are lacking. Because UM often micrometastasizes soon after its initial diagnosis, traditional treatments such as enucleation, resection, and radiation therapy are constantly disappointed [4, 5]. There are no systemic therapies that have been proven to effectively improve the clinical outcomes of metastatic UM. Immune checkpoint inhibitors like anti-PD1, anti-PDL1, and antiCTLA4 have been effectively employed in metastatic cutaneous melanoma, one of the biggest drawbacks for application of immunotherapy in UM is that only approximately 0% to 6% of response rate was observed in clinical use [6–8]. Exploration of immune cell characterization and identification of novel biomarkers for immunosuppression of UM are urgently required
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