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Supporting data for "Immunophenotyping of anti-PD-L1-treated hepatocellular carcinoma"

posted on 2023-09-11, 02:53 authored by Fu Wan SitFu Wan Sit

Hepatocellular carcinoma (HCC) is a deadly disease. The FDA recently approved the first immunotherapy, atezolizumab (anti-PD-L1) plus bevacizumab (anti-VEGF-A), for advanced HCC. Nonetheless, there are still patients not responding. Exploring how the tumour microenvironment is being altered upon anti-PD-L1 treatment helps unravel resistance mechanisms underlying anti-PD-L1 resistance. Using hydrodynamic tail vein injection (HDTVi), we established an anti-PD-L1 resistant HCC mouse model. We performed immunophenotyping of the tumour infiltrating immune cells utilising cytometry by Time-Of-Flight (CyTOF) and single-cell RNA sequencing (scRNA-seq). We discovered that anti-PD-L1 enhanced the infiltration of CD8+ T cells. Remarkably, several immune checkpoints were upregulated, accompanied by reduced effector functions. Anti-PD-L1 simultaneously induced T cell clonal expansion that shall aid in reinforcing immune response against tumour development. Together, these results suggest that anti-PD-L1 activates and expands T cells; however, these T cells are still in exhaustion due to other inhibitory receptors, rendering anti-PD-L1 ineffective in advanced HCC. Therefore, antibodies targeting the other immune checkpoints have considerable potential in restoring the therapeutic effects in combination with anti-PD-L1 to patients with advanced HCC. Submitted excel is the data for the figure included in the thesis, tab label corresponds to figure numbering


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