Project description:Tumor-infiltrating T lymphocytes (TILS) plays a pivotal role in immunotherapy, but the dynamic relationships of the T cells reacted on the therapy remains elusive. T cell receptor (TCR) repertoire, serving as lineage tags, could track these tumor-infiltrating T lymphocytes. Here, in order to deconvolve TILS heterogeneity after therapy in a comprehensive catalog, we presented single T-cell analysis by RNA-seq and TCR tracking of a 22,590 T cells from colorectal carcinoma under control conditions and during Stellera chamaejasme and anti-PD-1 activation. We reveal a highly complex microenvironment which profoundly molds T lymphocytes, as well as the combinatorial impact of TCR utilization on phenotypic diversity. scRNA-seq identified distinct CD8 T cells subtypes CD8 naïve and CD8 cytoxic cells(CD8 CTL), also, CD4 T cell subpopulations Regulatory T(Tregs) cells and T helper cell 17(Th-17). Stellera chamaejasme activation triggered CTSW, ICOS, etc. in CD8 T cells, whose the dramatic differentiation into from a single time point. At the same time, Stellera chamaejasme plus anti-PD-1 therapy have a strikingly effect on the balance between Tregs and Th-17. Our integrated analyses provide a powerful avenue to disclose the TILS in CRC based on TCR and demonstrate novel functional interactions among TILS subpopulations during Stellera chamaejasme plus anti-PD-1 therapy.
Project description:The interactions among Tumor-infiltrating T lymphocytes (TILS) induced by Stellera chamaejasme and anti-PD-1 therapy with Sing-cell Expression Profiling
Project description:An undescribed diterpene, stellerterpenoid A (1), and two undescribed sesquiterpenoids, stellerterpenoids B and C (2-3), together with six known compounds, prostratin (4) stelleraguaianone B (5), chamaejasnoid A (6), auranticanol L (7), wikstronone C (8), and oleodaphnone (9), were isolated from the roots of Stellera chamaejasme L. Their structures were elucidated by extensive spectroscopic data (1D, 2D NMR, IR, UV, and HR-ESI-MS). The absolute configuration of 1-3 was elucidated based on ECD calculation. Among them, stellerterpenoid A was a rare 13, 14-seco nortigliane diterpenoid and stellerterpenoid B was a guaiacane-type sesquiterpenoid with an unusual 1, 2-diketone moiety. The known stelleraguaianone B (5) exhibited moderate activity for suppressing NO production in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages cells with an IC50 value of 24.76 ± 0.4 μM. None of the compounds showed anti-influenza virus or anti-tumor activity in vitro.