Abstract
B and T lymphocyte attenuator (BTLA) is a newly identified immune checkpoint molecular belonging to the CD28 immunoglobulin superfamily. However, the expression and clinical value of BTLA in skin cutaneous melanoma (SKCM) has not been widely characterized. We found that BTLA levels were upregulated in metastatic melanoma compared to normal skin tissues and primary melanoma. Higher BTLA was also correlated with improved prognosis in SKCM based on several datasets. The multivariate Cox regression model revealed that BTLA was an independent survival indicator in metastatic melanoma. Tumor microenvironment analysis indicated BTLA was positively associated with the infiltrating levels of different immune cells and the activity of the anti-cancer immunity cycle. Importantly, BTLA accurately predicted the outcome of melanoma patients treated with MAGE-A3 blocker or first-line anti-PD-1. The present findings disclose that BTLA is a reliable biomarker for prognosis and immunotherapeutic response and might contribute to developing novel SKCM immunological treatment strategies.
Highlights
Skin cutaneous melanoma (SKCM) is estimated to be the fourth leading component cause of cancer-related mortality worldwide [1]
RNA-seq and sample profiles used for identification of B and T lymphocyte attenuator (BTLA) expression and prognostic value [GSE65904 [26], GSE53118 [27], GSE98394 [28]], validation of BTLA predictive value in metastatic melanoma patients treated with the anti-programmed death receptor-1 (PD-1) agent [GSE91061 [29] and Liu et al [30]], and MAGE-A3 blocker [GSE35640 [31]] were obtained from the Gene Expression Omnibus (GEO) database
Studies have established the singular role of BTLA as both a co-stimulator and co-inhibitor to activated cancerous CD8+ T cells [53]
Summary
Skin cutaneous melanoma (SKCM) is estimated to be the fourth leading component cause of cancer-related mortality worldwide [1]. Checkpoint-modulating agents targeting programmed death receptor-1 (PD-1) and its associated ligand (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) have been used as monotherapy or combination therapy monoclonal antibodies, showing long-term tumor containment and prolongation of survival [5]. Immunotherapy drugs, such as Pembrolizumab (anti-PD-1 antibody), Nivolumab (anti-PD-1 antibody), and Ipilimumab (anti-CTLA-4 antibody), have played an important role in the treatment of advanced-stage melanoma since 2011 [6,7,8]
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