Abstract
BackgroundThe tumor microenvironment (TME) involves infiltration of multiple immune cell subsets, which could influence the prognosis and clinical characteristics. The increasing evidence on the role of tumor-infiltrating lymphocytes (TILs) in primary and metastatic melanomas supports that the immune system is involved in the progression and outcomes of melanoma. However, the immune infiltration landscape in melanoma has not been systematically elucidated.MethodsIn this study, we used CIBERSORT and ESTIMATE algorithms to analyze immune infiltration pattern of 993 melanoma samples. Then we screened differential expression genes (DEGs) related to immune subtypes and survival. The immune cell infiltration (ICI) score was constructed by using principal-component analysis (PCA) based on immune signature genes from DGEs. Gene set enrichment analysis (GSEA) was applied to explore high and low ICI score related pathways. Finally, the predictive ability of ICI score was evaluated in survival prognosis and immunotherapy benefit.ResultWe identified three ICI clusters and three gene clusters associated with different immune subtypes and survival outcomes. Then the ICI score was constructed, and we found that high ICI score exhibited activated immune characteristics and better prognosis. High ICI score was significantly enriched in immune pathways and highly expressed immune signature genes. More importantly, we confirmed that melanoma patients with high ICI score had longer overall survival and rate of response to immunotherapy.ConclusionWe presented a comprehensive immune infiltration landscape in melanoma. Our results will facilitate understanding of the melanoma tumor microenvironment and provide a new immune therapy strategy.
Highlights
Malignant melanoma is one of the most severe skin cancers, with a higher risk of metastasis and mortality rates
The increasing evidence on the role of tumor-infiltrating lymphocytes (TILs) in primary and metastatic melanomas supports that the immune system is involved in the progression and outcomes of melanoma
Mucosal and uveal melanomas samples were excluded for significant difference from cutaneous melanoma in presentation, genetic profile, staging, response to treatment and patterns of progression [20, 21]
Summary
Malignant melanoma is one of the most severe skin cancers, with a higher risk of metastasis and mortality rates. PD-L1 expression, tumor mutation burden (TMB), and microsatellite instability-high (MSI-H) are the primary biomarkers for guiding the clinical practice of immune therapy and predicting survival benefit in several types of cancer [4, 5]. Neither PD-L1 expression nor TMB is a perfect biomarker for immune therapy prediction in melanoma, as responses are observed in PD-L1-negative and low TMB patients. Despite efforts to identify new biomarkers predictive of the benefits of immune therapy, such as ARID2 and tumor MHC-I expression [6, 7], no robust biomarker has been established to drive clinical practice. The increasing evidence on the role of tumor-infiltrating lymphocytes (TILs) in primary and metastatic melanomas supports that the immune system is involved in the progression and outcomes of melanoma. The immune infiltration landscape in melanoma has not been systematically elucidated
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