ScRNA-seq of Conjunctival melanoma-validation cohort 1
Description
Conjunctival melanoma (CoM) is a devastating malignancy with unignorable potential to develop distant metastasis. Despite various therapeutic strategies for distant metastatic CoM, the clinical outcomes remain unfavorable. Herein, we performed single-cell transcriptomic profiling of 57,005 cells obtained from normal conjunctival samples (n=3), conjunctival melanoma (n=6) and lymph node metastasis (n=3). Notably, we noticed a higher abundance of cancer-associated fibroblasts (CAFs) in the tumor microenvironment, correlated with enhanced angiogenic capacity and increased VEGFR expression in distal metastatic CoM. Additionally, we observed a significant decrease in the number of CD8+ T cells and an increase in the proportion of CD8+ T naive cells, contributing to a relatively quiescent immunological environment in distal metastatic CoM. Given these key changes during CoM progression, we launched a clinical trial (ChiCTR2100045061) of VEGFR blockade combined with anti-PD1 therapy for distant metastatic CoM patients, which exhibited capable tumor-inhibitory efficacy. Conclusively, our study uncovered the landscape and heterogeneity of the tumor microenvironment (TME) during CoM tumorigenesis and progression, empowering clinical decisions in the management of distal metastatic CoM. To our knowledge, this is the initial exploration to translate single cell RNA-sequencing (scRNA-seq) analysis to a clinical trial dealing with cancer, providing a novel concept by accommodating scRNA-seq data in cancer therapy.