Aging-US: An immune subtype of uveal melanoma with a poor prognosis09-08-2021
Aging-US published a Special Collection on Eye Disease which included "Immunological analyses reveal an immune subtype of uveal melanoma with a poor prognosis" which reported that uveal melanoma is an aggressive intraocular malignancy that often exhibits low immunogenicity.
Metastatic uveal Melanoma samples frequently exhibit monosomy 3 or BAP1 deficiency. In this study, the authors used bioinformatic methods to investigate the immune infiltration of uveal melanoma samples in public datasets.
The Kaplan-Meier method and log-rank test were used to assess the prognostic value of particular immune cells and genes in samples. These authors used CIBERSORT and ESTIMATE with RNA-seq data from The Cancer Genome Atlas and the GSE22138 microarray dataset to determine the sample-level immune subpopulations.
Figure 6. The prognostic value of individual immune genes in UM. (A) Kaplan-Meier survival curves demonstrate that elevated levels of CD8A (P<0.0001), HLA-A (P<0.0001), HLA-B (P=0.0001), HLA-C (P=0.0003) and HLA-DRA (P=0.0001) were consistently associated with worse OS in the UM dataset of TCGA. (B) Kaplan-Meier survival curves demonstrate that elevated levels of CD8A, HLA-A, HLA-B, HLA-C and HLA-DRA were consistently associated with a worse PFI in the UM dataset of TCGA (log-rank test, P<0.05). (C) Kaplan-Meier survival curves demonstrate that elevated levels of CD8A (P=0.06), HLA-A (P=0.02), HLA-B (P=0.002), HLA-C (P=0.007) and HLA-DRA (P=0.03) were consistently associated with worse metastasis-free survival in the Laurent UM dataset (n=63; log-rank test, P<0.05).
Dr. Zhaoyang Wang and Dr. Xianqun Fan said, "Immune heterogeneity within the tumor microenvironment has been linked to the drug sensitivity and prognosis of patients with various cancer types."
Profiling of immune signatures might uncover biomarkers for targeted therapy and clinical outcome assessment. Uveal melanoma (UM) is the most common aggressive intraocular malignancy in adults, and originates from the uveal tract.
Monosomy 3 tumors were found to be enriched for genes in immune pathways such as interferon signaling, T cell invasion and cytotoxicity. Mutation of GNA11/GNAQ was not found to significantly alter the immune infiltration and HLA Class I expression in UM patients. Characterizing the immunological features of UM may provide novel immune biomarkers for prognostic assessment and immunotherapy.
Enhancing the cytolytic functions of infiltrating lymphocytes can significantly improve antitumor immunity. However, due to the low levels of cytotoxic cells in the tumor microenvironment, non-responsiveness to immunotherapy remains a clinical challenge.
The Wang/Fan Research Team concluded in their Aging-US Research Output that gene expression profiling of UM patients treated with immune checkpoint blockers has advanced the application of genomic data to tumor immunology.
The authors hope that large sequencing data from UM patients undergoing immune checkpoint blocker treatment will emerge in the future. The immune features reported herein should be considered for integration into prognostic models or explored as predictors of adjuvant immune therapy responsiveness in patients with BAP1-deficient UM.
The Volti/Vinciguerra Research Team concluded in their Aging-US Research Output, "we suggest that strategies aiming at decreasing the expression of histone variant macroH2A1 , might effectively hamper the aggressiveness of UM cells, by inhibiting their mitochondrial phosphorylation. This could be a novel promising therapeutic strategy against UM ."
Full Text - https://www.aging-us.com/article/102693/text
Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways.