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Here, we report that\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    (\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    ) triggers caspase-3\u2013dependent pyroptosis in murine CRC MC38 cells, characterized by GSDME cleavage, intracellular reactive oxygen species (ROS) accumulation, and the release of damage-associated molecular patterns (DAMPs). This form of immunogenic cell death promotes robust inflammatory cytokine secretion, upregulation of PD-L1 on tumor cells, and functional maturation of bone marrow\u2013derived dendritic cells (BMDCs) in vitro. In vivo, intratumoral injection of\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    leads to significant reprogramming of the TME, including increased expression of proinflammatory genes, DC maturation, and enhanced infiltration of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T lymphocytes. Notably, combination therapy with\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    and an anti-PD-L1 antibody results in synergistic tumor regression, markedly outperforming either monotherapy, without inducing detectable systemic toxicity. Together, our findings reveal that\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    -induced pyroptosis serves as a potent immunogenic stimulus that reshapes the CRC tumor microenvironment and overcomes resistance to immune checkpoint blockade. This strategy represents a promising approach to enhance immunotherapy efficacy in poorly immunogenic solid tumors.\n                  <\/jats:p>","DOI":"10.1007\/s00262-025-04266-y","type":"journal-article","created":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T22:04:11Z","timestamp":1767477851000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pseudomonas aeruginosa induces tumor pyroptosis and immune activation to enhance checkpoint blockade in colorectal cancer"],"prefix":"10.1007","volume":"75","author":[{"given":"Yanan","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxi","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningyi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwei","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,3]]},"reference":[{"key":"4266_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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