Comprehensive analysis of single cell and bulk RNA sequencing reveals the heterogeneity of melanoma tumor microenvironment and predicts the response of immunotherapy.

Abstract

Background: Tumor microenvironment (TME) heterogeneity is an important factor affecting the treatment response of immune checkpoint inhibitors (ICI). However, the TME heterogeneity of melanoma is still widely characterized.

Methods: We downloaded the single-cell sequencing data sets of two melanoma patients from the GEO database, and used the "Scissor" algorithm and the "BayesPrism" algorithm to comprehensively analyze the characteristics of microenvironment cells based on single-cell and bulk RNA-seq data. The prediction model of immunotherapy response was constructed by machine learning and verified in three cohorts of GEO database.

Results: We identified seven cell types. In the Scissor⁺ subtype cell population, the top three were T cells, B cells and melanoma cells. In the Scissor^- subtype, there are more macrophages. By quantifying the characteristics of TME, significant differences in B cells between responders and non-responders were observed. The higher the proportion of B cells, the better the prognosis. At the same time, macrophages in the non-responsive group increased significantly. Finally, nine gene features for predicting ICI response were constructed, and their predictive performance was superior in three external validation groups.

Conclusion: Our study revealed the heterogeneity of melanoma TME and found a new predictive biomarker, which provided theoretical support and new insights for precise immunotherapy of melanoma patients.