Abstract
Abstract Intro: The number of undergoing clinical trials using more than one immune checkpoint inhibitor is rising rapidly. Previously, we have observed CD4 CD8 double-positive T cells (Figure 1) from checkpoint inhibitor responder in advanced HCC patient. To further investigate the genomic difference between CD4 CD8 double-positive T (DP T) cell and conventional CD4, CD8 T cells, we have applied GO, KEGG, and Reactone database to compare. Material and method: Two responders showed a partial response to PD-1/PD-L1 inhibitor treatment with advanced HCC were included. DP T cells were measured with Carl Zeiss Laser Scanning Microscopy (LSM) 780 (Zeiss) at Faculty Core Facility. Blood samples from responders were stained with an antibody cocktail containing CD3, CD4 and CD8 T cells. To visualise the labelling cells, CD3, CD4 and CD8 surface fluorescence was shown in yellow, violet and green dots respectively. Conventional CD4, CD8 T cells and DP T cells were further sorted using the same staining protocol before extraction. RNA extraction were immediately applied after cell sorting, where CD4 CD8 double-negative T (DN T) cells were also included. All patients were seen at the Department of Medical Oncology, Queen Mary Hospitals. Blood samples were collected after the treatment along with clinical routine blood test. Results: A total number of 3723 and 4653 genes respectively were differentially expressed in DP T cell versus CD8 T cell and DP T cell versus CD4 T cell in responder 1, whereas a total 11117 differential expressed genes were measured in DP T cell and DN T cell. In responder 2, a total number of 6439 genes were differentially expressed in DP T versus CD8 T cell, while a total number of 316 and 488 differential expressed genes were measured in DP T cell versus CD4 T cell and DP T cell versus DN T cell. GO, KEGG and Reactone database analysis indicated cytokine receptor, cell cytotoxicity and cell activation enrichment in DP T cell compared to conventional CD4 or CD8 T cell. Citation Format: Vox Ting, Carmen Chak-Lui Wong, Yok Lam Kwong, Thomas Chung Cheung Yau. Genomic difference of CD4 CD8 double-positive T cells versus conventional CD4 T cells and CD8 T cells in responders undergoing immunotherapy in advanced HCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 487.
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