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- W2890917729 abstract "12104 Background: Combination of anti-PD1/L1 and anti-CTLA4 is under investigation for treatment of multiple tumors. However, how this combination modifies the immune micro-environment of tumors is not well understood. Using single cell RNA sequencing (scRNAseq), we are systematically characterizing the ex vivo cellular and molecular effects of Durvalumab (D) and Tremelimumab (T) treatment on NSCLC tumors. Methods: Commercially available dissociated NSCLC tumor was treated with low dose interleukin-2 (IL-2) plus D, D+T or isotype control (IsoCtrl) at 20ug/ml each. For scRNAseq, T cells were isolated using αCD4 and αCD8 beads. Over 20,000 immune cells were profiled on D7 after treatment using 10X genomics. Exhausted T cells were defined based on the signature by Singer et al. (2016). Cell clustering and differential expression analyses were conducted using R package Seurat. Functional enrichment analyses, including KEGG and GO were performed by ClusterProfiler. Results: At D7 of D or D+T treatment, intracellular IFNG expression increased 60 and 80%, respectively. scRNAseq results were consistent with this functional data, showing 6% and 12% more IFNG expression in CD4+/CD8+ T cells following D and D+T, respectively. Checkpoint inhibitor expression (PDCD1, CTLA4, TIGIT, LAG3, HAVCR2) increased 4-9% and 7-15% upon D or D+T treatment, respectively. D and D+T treatment increased fraction of total CD4+ cells from 21% to 27% and 28%, respectively; however, there was a reduction in the specific CD4 subfraction of T regs (CD4+FOXP3+) in both treatments compared to IsoCtrl. D+T treatment shifted the molecular phenotype of exhausted T cells toward a more activated state by inducing a significant upregulation of PTPRCAP, ITGB1, and KLF2, genes important for T cell activation and/or reduced T reg function. Conclusions: Single-cell profiling of NSCLC tumor suggest that D+T treatment alters the molecular profile of exhausted T cells and T regs to generate a more active phenotype, which may contribute to clinical benefit for patients treated with this combination." @default.
- W2890917729 created "2018-09-27" @default.
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- W2890917729 date "2018-05-20" @default.
- W2890917729 modified "2023-09-27" @default.
- W2890917729 title "Single-cell profiling of NSCLC tumor treated with Durvalumab and in combination with Tremelimumab." @default.
- W2890917729 doi "https://doi.org/10.1200/jco.2018.36.15_suppl.12104" @default.
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