STARTRAC analyses of scRNAseq data from tumor models reveal T cell dynamics and therapeutic targets

• DOI: 10.1084/jem.20201329
• Publication Date: 2021-04-26T14:03:10Z
• Authors: Dev Bhatt; Boxi Kang; Deepali Sawant; Liangtao Zheng; Kristy Perez; Zhiyu Huang; Laura Sekirov; Dan Wolak; Julie Y. Huang; Xian Liu; Jason DeVoss; Paolo S. Manzanillo; Nathan Pierce; Zemin Zhang; Antony Symons; Wenjun Ouyang
• Keywords: CD4-Positive T-Lymphocytes; Mice, Inbred BALB C; 0303 health sciences; Programmed Cell Death 1 Receptor; CD8-Positive T-Lymphocytes; Th1 Cells; T-Lymphocytes, Regulatory; Technical Advances and Resources; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; Mice; 03 medical and health sciences; Lymphocytes, Tumor-Infiltrating; Cell Line, Tumor; Neoplasms; Animals; Female

Single-cell RNA sequencing is a powerful tool to examine cellular heterogeneity, novel markers and target genes, therapeutic mechanisms in human cancers animal models. Here, we analyzed single-cell data of T cells obtained from multiple mouse tumor models by PCA-based subclustering coupled with TCR tracking using the STARTRAC algorithm. This approach revealed various differentiated cell subsets activation states, correspondence between tumors. analyses demonstrated peripheral that were developmentally connected tumor-infiltrating CD8+ cells, CD4+ Th1 reg cells. In addition, large amounts paired TCRα/β sequences enabled us identify specific enrichment public clones tumor. Finally, identified CCR8 as tumor-associated marker could preferentially deplete We showed CCR8-depleting antibody treatment provided benefit CT26 tumors synergized anti–PD-1 MC38 B16F10