Regulation of Specific Cell Clusters in TCR-T Cells Responding to Differential Expression of Tumor PD-L1

Renpeng Ding; Shang Liu; Huanyi Chen; Bin Kang; Radoje Drmanac; Ying Gu

Authors

Renpeng Ding
Shang Liu
Huanyi Chen
Bin Kang
Radoje Drmanac
Ying Gu

Keywords:

TCR-T, PD-L1, scRNA-seq, cell clusters, gene expression

Abstract

PD-L1 signaling is essential in regulating T cell function and keeping the balance of tumor microenvironment, but its role in modifying TCR-T cell cytotoxicity remains unknown. MART-1-specific TCR-T cells (TCR-T MART-1 ) were stimulated by MEL-526 tumor cells expressing different proportions of PD-L1 and used to perform cytotoxicity assays and single-cell RNA sequencing. Percentage changes of different specific cell clusters were analyzed. The percentage of cluster HLA-DR + CD38 + CD8 + was upregulated after antigen stimulation, and tumor PD-L1 modified TCR-T cell function through downregulating the percentages of HLA-DR + CD28 + CD8 + and HLA-DR + CD38 + CD8 + subsets which were higher in TCR-T MART-1 than in T null .

Downloads

How to Cite

Regulation of Specific Cell Clusters in TCR-T Cells Responding to Differential Expression of Tumor PD-L1. (2020). Global Journal of Medical Research, 20(F8), 11-19. https://medicalresearchjournal.org/index.php/GJMR/article/view/2188

Download Citation

References

L Zou, Chen (2008) Inhibitory B7-family molecules in the tumour microenvironment. 8(6), 467-477.

Jianxiang Zhang, Lingyu Wang (2019) The Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review. 18, 1533033819831068.

Zhu Jianhong, Zhong Junjie (2018) Engineered T Cells for glioblastoma therapy. 1(4), 125.

Miyuki Nishimura, Hisanori Umehara, Takashi Nakayama, Osamu Yoneda, Kunio Hieshima, Mayumi Kakizaki, Naochika Dohmae, Osamu Yoshie, Toshio Imai (2002) Dual Functions of Fractalkine/CX3C Ligand 1 in Trafficking of Perforin+/Granzyme B+ Cytotoxic Effector Lymphocytes That Are Defined by CX3CR1 Expression. 168(12), 6173-6180.

J Bottcher, M Beyer, F Meissner, Z Abdullah, J Sander, B Hochst (2015) Functional classification of memory CD8(+) T cells by CX3CR1 expression. 6, 8306.

Limin Xing, Chunyan Liu, Rong Fu, Huaquan Wang, Jun Wang, Xiao Liu, L Feng, Lijuan Li, Hui Liu, Honglei Wang, Tian Zhang, Zonghong Shao (2014) CD8+HLA-DR+ T cells are increased in patients with severe aplastic anemia. 10(3), 1252-1258.