AI Article Synopsis
- Tumors can create an immunosuppressive environment by generating specialized cells like tumor-educated dendritic cells (TEDCs), which aid in tumor progression.
- In this study, researchers discovered that the transcription factor EB (TFEB) is elevated in TEDCs due to influence from cancer cell signals, and knocking down TFEB enhances TEDCs’ ability to mature and promote immune responses.
- By inhibiting TFEB in TEDCs, tumors showed reduced growth and increased immune cell infiltration, suggesting that targeting TFEB could be a promising strategy for cancer immunotherapy.
Article Abstract
Tumors can induce the generation and accumulation of immunosuppressive cells in -the tumor microenvironment (TME). Among them, tumor-educated dendritic cells (TEDCs) involved in tolerance induction contribute greatly to the progression of tumors. However, the mechanisms governing the immunosuppressive function of dendritic cells in the TME are unclear. In this study, we found that the expression of transcription factor EB (TFEB) was significantly increased in TEDCs induced by cancer cell supernatant. TFEB knockdown significantly promoted the differentiation and maturation of TEDCs, with upregulated expression of CD11c and costimulatory molecules (CD86 and MHC-II) but reduced expression of the inhibitory molecule PD-L1, and enhanced their ability to induce Th1 proliferation and differentiation. Moreover, TEDCs with TFEB knockdown significantly reduced tumor growth with increased infiltration of CD11cMHC-II dendritic cells and effector T cells in tumor masses, thus leading to a delay in tumor progression. These findings demonstrate a critical role of TFEB in regulating the immunosuppression of TEDCs, with potential implications as an antitumor immune therapeutic approach.
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| http://dx.doi.org/10.1016/j.molimm.2022.04.011 | DOI Listing |
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