Version 1
: Received: 15 April 2024 / Approved: 16 April 2024 / Online: 16 April 2024 (10:47:24 CEST)
How to cite:
Yu, X.; Xu, J. TWIST1 Drives Immune Evasion through Upregulating PD-L1 Expression in Breast Cancer. Preprints2024, 2024041047. https://doi.org/10.20944/preprints202404.1047.v1
Yu, X.; Xu, J. TWIST1 Drives Immune Evasion through Upregulating PD-L1 Expression in Breast Cancer. Preprints 2024, 2024041047. https://doi.org/10.20944/preprints202404.1047.v1
Yu, X.; Xu, J. TWIST1 Drives Immune Evasion through Upregulating PD-L1 Expression in Breast Cancer. Preprints2024, 2024041047. https://doi.org/10.20944/preprints202404.1047.v1
APA Style
Yu, X., & Xu, J. (2024). TWIST1 Drives Immune Evasion through Upregulating PD-L1 Expression in Breast Cancer. Preprints. https://doi.org/10.20944/preprints202404.1047.v1
Chicago/Turabian Style
Yu, X. and Jianming Xu. 2024 "TWIST1 Drives Immune Evasion through Upregulating PD-L1 Expression in Breast Cancer" Preprints. https://doi.org/10.20944/preprints202404.1047.v1
Abstract
In breast cancer, epithelial-mesenchymal transition (EMT) is positively associated with programmed death ligand 1 (PD-L1) expression and immune escape, and TWIST1 induces EMT and cancer metastasis. However, how TWIST1 regulates PD-L1 and immune evasion is unknown. This study analyzed TWIST1 and PD-L1 expression in breast cancers, investigated the mechanism for TWIST1 to regulate PD-L1 transcription, and assessed the effects of TWIST1 and PD-L1 in cancer cells on the cytotoxicity of CD8+ effector T cells. Interestingly, TWIST1 expression is associated with high-level PD-L1 in triple negative breast cancers (TNBCs). Overexpression and knockdown of TWIST1 robustly upregulates and downregulate PD-L1 expression, respectively. TWIST1 binds to the PD-L1 promoter and recruits the TIP60 acetyltransferase complex in a BRD8-dependent manner to promote PD-L1 expression, which drives immune escape of breast cancer cells by accelerating the exhaustion of CD8+ T cells. Accordingly, knockdown of TWIST1 or BRD8 or blockade of PD-L1 with a PD-L1 antibody significantly enhances CD8+ T cells to inhibit breast cancer cell growth. These results demonstrate that TWIST1 directly induces PD-L1 expression in breast cancer cells to drive immune evasion. Targeting TWIST1, BRD8 or PD-L1 in TNBC should facilitate CD8+ T cell-mediated immune therapy. TWIST1 may also serve as a biomarker for anti-PD-L1 immunotherapy.
Keywords
Breast cancer; EMT; TWIST1; metastasis; immunosuppression; PD-L1; immune-checkpoint-inhibitor therapy
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
