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bioRxiv · 10.1101/2024.11.11.623110

TLL1 knockdown attenuates prostate cancer progression by enhancing antitumor immunity

hao, j.·He, J.·Hu, H.·Wu, X.·Zhu, Z.·Zhao, X.·Li, L.·Ruan, Y.·Yang, J.·Fu, M.·Zhang, K.·Gao, P.·Dong, X.
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Abstract

Due to the inevitable progression to castration-resistant prostate cancer (CRPC) following treatment with androgen deprivation therapy (ADT), it is essential to develop novel treatment approaches for managing CRPC. Here we showed that metalloproteinase TLL1 was positively associated with prostate cancer aggressiveness. Mechanistically, TLL1 promoted prostate cancer cells migration and metastasis through cleaving latent TGF-{beta}1 to activate TGF-{beta} signaling pathway. Moreover, LINC01179 interacted with Miz1 to attenuate TLL1 expression and LINC01179 impaired prostate cancer cell proliferation and migration ability by suppressing TLL1 expression to deactivate TGF-{beta} signaling activity. Meanwhile, we observed that TLL1 increased the expression of PD-L1 by activating TGF-{beta} signaling pathway and TLL1 depletion enhanced the antitumor efficacy by anti-PD-1 antibody via augmenting the infiltration proportions of CD8+ T cells in tumors. In addition, T cell-specific overexpression of TLL1 disrupted T cell development in the thymus. TLL1 overexpression in T cells accelerated RM-1 prostate tumor growth in mice by decreasing the infiltration of CD8+ T cells into tumors. Collectively, our results revealed that TLL1 may be a potential therapeutic target to alter prostate cancer progression.

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hao, j., He, J., Hu, H., Wu, X., Zhu, Z., Zhao, X., Li, L., Ruan, Y., Yang, J., Fu, M., Zhang, K., Gao, P., Dong, X.. 2024-11-12. TLL1 knockdown attenuates prostate cancer progression by enhancing antitumor immunity. https://doi.org/10.1101/2024.11.11.623110

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