Journal
MOLECULAR IMMUNOLOGY
Volume 160, Issue -, Pages 32-43Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2023.06.004
Keywords
Shkbp1; CD8+T cells; Tumor growth; Cancer immunotherapy; Transgenic mice
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CD8 + effector cells play a crucial role in immune surveillance and adaptive immunity against cancer cells. Knockout of the Shkbp1 gene increases the number and enhances the function of CD8 + T cells in the spleen. This study suggests that Shkbp1 may be a potential target in cancer immunotherapy.
CD8 + effector cells are highly skilled in immune surveillance and contribute to adaptive immunity against cancer cells. An increasing number of molecular factors affecting T-cell differentiation may alter T-cell function by increasing or decreasing the capacity of the immune system to kill cancer cells. Here, Sh3kbp1 binding protein 1 (Shkbp1), known as CIN85 binding protein or SETA binding protein, was found to be expressed in immune organs and immune cells. Shkbp1 knockout mice presented abnormal red and white pulp structures in spleen. Shkbp1 knockout increased CD8 + T cell number in spleen and enhanced the function of isolated CD8 + T cells from Shkbp1 knockout mice. The subcutaneous melanoma model in Shkbp1 knockout mice showed that tumor growth was inhibited, and the infiltration of CD8 + T cells in tumor tissue was increased. Furthermore, adenoviral therapy targeting Shkbp1 indicated that knockout of Shkbp1 increased CD8 + T cells and inhibited tumor growth. This study provides new insights into the role of Shkbp1 in CD8 differentiation and functions, suggesting that Shkbp1 may be a new, potential target in cancer immunotherapy.
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