Cancer immunotherapies have revolutionized the treatment of cancer. To better understand the dynamic changes of T cell states during tumor progression, we profiled TCR sequences and transcriptomes of ~40,000 T cells from matched xenograft MC38 cancer cell line and spleen samples of 12 mice. Comparing the gene expression profiles of T cells collected in 10-day and 20-day samples, we observed obvious differences of T cell composition, such as higher CD8 and lower CD4 T cells in 20-day tumors. Unsupervised clustering revealed two subsets of T cells specific to early tumors, recapitulating important markers, such as TCF7, which has recently been reported to be a valid predictor of immune checkpoint blockade therapies in melanoma. Additionally, a unique CD8 cluster, expressing markers of T cell activation and exhaustion, was found to appear only in late tumors. We also observed subpopulations of TCRαβ+ CD3+/CD4-/CD8- double negative (DN) T cells, which have not been well-characterized in the tumor microenvironment. Our analysis revealed three clusters of DN cells: 1) an effector-like group with FCER1G and XCL1 high expression, and high interferon production; 2) a regulatory population expressing high level of Foxp3 and IL2ra, which has been previously reported in autoimmune disorders; 3) a naïve-like population with CCR7 expression. These findings indicate that the DN T cell population may span a wide-spectrum of functionalities that similar to CD4 or CD8 single positive conventional T cells. Our study, for the first time, provided a high-resolution dynamic landscape of T cell state and identified rare T cell subgroups associated with cancer progression.

Citation Format: Hongyi Zhang, Longchao Liu, Jiahui Chen, Bo Li. Investigation of T cell dynamic changes in tumor progression by using sing-cell data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-145.