Targeting cathepsin B by cycloastragenol enhances anti-tumor immunity via inhibiting MHC-1 degradation and promoting the presentation of tumor antigen
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE197229 | GEO | 2023/02/22
REPOSITORIES: GEO
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Project description:Purpose:We want to elaborate the specific mechanism of CAG inhibiting the growth of transplanted mouse colon cancer cell MC38. Methods:After MC38 cells were inoculated into C57BL/6 mice for 6 days, the mice were evenly divided into PBS group and CAG group, and PBS and CAG (50mg / kg) were administered by gavage every day. On the 18th day, the mouse tumors were removed, and one tumor was selected to prepare single cell suspension for 10x-scRNA-seq and 10x-scATAC-seq. Results:We found that CAG promoted the antigen-presenting function of tumor cells and enhanced the killing ability of CD8 T cells. Conclusions:CAG enhances the antitumor immunity of CD8 T cells by promoting the antigen presentation of tumor cells.
2023-02-22 | GSE197227 | GEO
Project description:Purpose:We want to elaborate the specific mechanism of CAG inhibiting the growth of transplanted mouse colon cancer cell MC38. Methods:After MC38 cells were inoculated into C57BL/6 mice for 6 days, the mice were evenly divided into PBS group and CAG group, and PBS and CAG (50mg / kg) were administered by gavage every day. On the 18th day, the mouse tumors were removed, and one tumor was selected to prepare single cell suspension for 10x-scRNA-seq and 10x-scATAC-seq. Results:We found that CAG promoted the antigen-presenting function of tumor cells and enhanced the killing ability of CD8 T cells. Conclusions:CAG enhances the antitumor immunity of CD8 T cells by promoting the antigen presentation of tumor cells.
2023-02-22 | GSE197228 | GEO
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Project description:Neutrophil elastase (NE) is an innate immune cell-derived inflammatory mediator that we have shown increases the presentation of tumor-associated peptide antigens in breast cancer. In this study, we extend these observations to show that NE uptake has a broad effect on enhancing antigen presentation by breast cancer cells. We show that NE increases human leukocyte antigen (HLA) class I expression on the surface of breast cancer cells in a concentration and time-dependent manner. HLA class I upregulation requires internalization of enzymatically active NE. Western blots of NE-treated breast cancer cells confirm that the expression of total HLA class I as well as the antigen-processing machinery proteins TAP1, LMP2, and calnexin does not change following NE treatment. This suggests that NE does not increase the efficiency of antigen processing; rather, it mediates the upregulation of HLA class I by stabilizing and reducing membrane recycling of HLA class I molecules. Furthermore, the effects of NE extend beyond breast cancer since the uptake of NE by EBV-LCL increases the presentation of HLA class I-restricted viral peptides, as shown by their increased sensitivity to lysis by EBV-specific CD8+ T cells. Together, our results show that NE uptake increases the responsiveness of breast cancer cells to adaptive immunity by broad upregulation of membrane HLA class I and support the conclusion that the innate inflammatory mediator NE enhances tumor cell recognition and increases tumor sensitivity to the host adaptive immune response.
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