Single-cell sequencing reveals the landscape of the tumor microenvironment in malignant fibrous histiocytoma

Abstract

Background: Malignant fibrous histiocytoma (MFH) is an invasive pleomorphic soft tissue sarcoma with a high degree of malignancy and poor prognoses, and is prone to recurrence and metastasis. The pathophysiology remains elusive and its therapeutic options are limited. The 5-year recurrence rate of patients is 36% to 61%. Progress in single-cell RNA sequencing (scRNA-seq) provides an opportunity to dissect the pathophysiology of human diseases at unprecedented resolution, particularly in the diseases lacking animal models, such as MFH.Methods: We performed scRNA-seq on tumor tissues and adjacent muscle tissues from a patient with MFH. We identified Cell types and the corresponding marker genes by single-cell RNA sequencing. Malignant cells of fibroblasts were evaluated by CopyKAT analysis and differentially expressed genes of sequencing.Results: We identified PDCD1, CTLA4 and TIGIT as potential targets. We further showed that C2_Exhausted CD4+ Treg and C1_Exhausted CD8+ T cell highly expressed PDCD1, CTLA4 and TIGIT. Intervention via PD-1 immune checkpoint inhibitor (tirelizumab) enabled disease control and reduced tumor immunosuppression. Conclusion: Thus, scRNA-seq analyses guide a successful therapeutic intervention in the MFH patient, improve our understanding of complex human diseases and provide an alternative approach to personalized medicine.