TRAF6-overexpressing dendritic cells loaded with MUC1 peptide enhance anti-tumor activity in B16-MUC1 melanoma-bearing mice.

Jingjing Wang, Yu Liu, Weihua Ni, Xinjie Wu, Jianhong Zhou, Zenan Zhang, Hongyue Zhou, Nannan Zhang, Mengyu Jiang, Qianyu Sang, Hongyan Yuan, Guixiang Tai

International immunopharmacology 2022 Jun

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Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) signaling is a critical positive mechanism for the development, homeostasis and activation of immune cells. We investigated the effect of TRAF6 overexpression on dendritic cells (DCs) maturation. TRAF6-overexpressing DCs had increased expression of costimulatory molecules, major histocompatibility complex (MHC) molecules and IL-12 expression. This indicated that TRAF6 promoted the maturation of DCs and indirectly promoted Th1 activation. The antitumor activities between TRAF6-overexpressing DCs and control DCs were compared by administering DCs pulsed with mucin 1 (MUC1) Ag peptide in a therapeutic human MUC1-overexpressing mouse B16 melanoma cells (B16-MUC1) model. Administration of TRAF6-overexpressing DCs significantly inhibited the growth of B16-MUC1 tumors, accompanied by an increase in MUC1-specific Th1 responses and Tc1 responses, as well as a decrease in Tregs levels. TRAF6 signaling has been found to be involved in DCs maturation and Th1 activation in vitro, as well as therapeutic tumor models in vivo, indicating that TRAF6-overexpressing DCs may be a promising approach for cancer immunotherapy. Copyright © 2022 Elsevier B.V. All rights reserved.

Citation

Jingjing Wang, Yu Liu, Weihua Ni, Xinjie Wu, Jianhong Zhou, Zenan Zhang, Hongyue Zhou, Nannan Zhang, Mengyu Jiang, Qianyu Sang, Hongyan Yuan, Guixiang Tai. TRAF6-overexpressing dendritic cells loaded with MUC1 peptide enhance anti-tumor activity in B16-MUC1 melanoma-bearing mice. International immunopharmacology. 2022 Jun;107:108667