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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\u00a0vitro experiments and gene sequencing results showed that pyroptotic macrophages could upregulate the expression of TLR4 through secreting inflammatory cytokines IL\u201018. Upregulated TLR4 activated its downstream NF\u2010\u03baB anti\u2010apoptotic signaling pathway, thus leading to malignant proliferation and chemotherapy resistance of tumor cells. Moreover, the expression of factors such as XIAP in the NF\u2010\u03baB anti\u2010apoptotic 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\u2010depth 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.<\/jats:p>","DOI":"10.1111\/cas.16180","type":"journal-article","created":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T08:05:05Z","timestamp":1712995505000},"page":"2444-2460","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pyroptotic macrophages promote proliferation and chemotherapy resistance of <scp>peripheral T\u2010cell lymphoma<\/scp> via <scp>TLR4<\/scp> signaling pathway"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8809-4969","authenticated-orcid":false,"given":"Han","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Harbin Medical University Cancer Hospital Harbin Medical University  Harbin 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