Pyroptotic macrophages promote proliferation and chemotherapy resistance of peripheral T‐cell lymphoma via TLR4 signaling pathway
Male
0303 health sciences
Macrophages
NF-kappa B
Interleukin-18
Lymphoma, T-Cell, Peripheral
Apoptosis
Middle Aged
Prognosis
Toll-Like Receptor 4
Gene Expression Regulation, Neoplastic
Mice
03 medical and health sciences
Drug Resistance, Neoplasm
Cell Line, Tumor
Pyroptosis
Humans
Animals
Female
ORIGINAL ARTICLE
Signal Transduction
Cell Proliferation
DOI:
10.1111/cas.16180
Publication Date:
2024-04-13T08:05:05Z
AUTHORS (11)
ABSTRACT
AbstractPeripheral T‐cell lymphoma (PTCL) is a highly aggressive type of non‐Hodgkin's lymphoma with a poor prognosis. Pyroptosis is a newly discovered procedural cell death mode, which has been implicated to occur in both tumor cells and immune cells. However, the occurrence and effect of pyroptosis on PTCL remain unclear. Here, we found that pyroptosis occurred in interstitial macrophages of PTCL rather than in tumor cells. In clinical specimens, macrophage pyroptosis was associated with a poor prognosis of PTCL. In vitro experiments and gene sequencing results showed that pyroptotic macrophages could upregulate the expression of TLR4 through secreting inflammatory cytokines IL‐18. Upregulated TLR4 activated its downstream NF‐κB anti‐apoptotic signaling pathway, thus leading to malignant proliferation and chemotherapy resistance of tumor cells. Moreover, the expression of factors such as XIAP in the NF‐κB anti‐apoptotic pathway was downregulated after the knockdown of TLR4, and the malignant promotion effect of pyroptotic macrophages on PTCL cells was also reversed. Our findings revealed the mechanism of pyroptotic macrophages promoting the malignant biological behavior of PTCL and elucidated the key role of TLR4 in this process. In‐depth analysis of this mechanism will contribute to understanding the regulatory effect of PTCL by the tumor microenvironment and providing new ideas for the clinical treatment of PTCL.
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