CD8+ T-Cell Number and Function are Altered by Shkbp1 Knockout Mediated Suppression of Tumor Growth in Mice

Abstract

Abstract CD8 + effector cells are highly skilled in/at 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 and SETA binding protein, was found to be expressed in immune organs and immune cells. Shkbp1 knockout mice presented abnormal red and white pulp in spleen tissue. Shkbp1 knockout increased the cell number in the spleen and enhanced the function of isolated CD8 + T cells from Shkbp1 knockout mice. Data on subcutaneous melanoma in Shkbp1 knockout mice showed that melanoma 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 as a cancer immunotherapy, suggesting that Shkbp1 may be a new, potential target in cancer immunotherapy.