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Programmed death ligand-1 (PD-L1) has shown a close relationship with inflammatory disorder among animal models and patients. We aimed to investigate the potential beneficial immunologic mechanisms of anti-PD-L1 on monocyte dysfunction of mice with sepsis. Firstly, we assessed the potential association between PD-L1 expression on monocyte subsets and sepsis severity as well as 28-day mortality. In this study, 52 septic patients, 28 septic shock patients, and 40 healthy controls were enrolled and their peripheral whole blood was examined by flow cytometry. Then, cecal ligation and puncture (CLP) were performed for establishing the mouse sepsis model. Subsequently, effects of anti-PD-L1 antibody on monocyte subset, major histocompatibility complex II (MHC II) expression, cytokine production, and survival were investigated. PD-L1 expression on the classical monocytes (CD14\u2009+\u2009+\u2009CD16\u2009\u2212) was significantly upregulated among septic shock patients and the 28-day death group than non-septic shock group and 28-day survival group (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05). Compared to septic mice, anti-PD-L1-treated mice had significantly elevated percentages of major histocompatibility complex (MHC) II on peripheral Ly6c\n                    <jats:sup>hi<\/jats:sup>\n                    monocyte at 24\u00a0h after CLP. Our results showed that the anti-PD-L1 antibody markedly decreased the level of serum inflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-\u03b1, and IL-10 in sepsis mice at 24\u00a0h, 48\u00a0h, and 72\u00a0h, respectively (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05). The survival rate of CLP mice was significantly improved by anti-PD-L1 antibody treatment. Classical monocytes with high expression of PD-L1 were thought to be connected with sepsis progression. The PD-L1 blockade protects from sepsis, at least partially by inhibiting the reversal of monocyte dysfunction.\n                  <\/jats:p>","DOI":"10.1007\/s10753-023-01897-0","type":"journal-article","created":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T02:02:06Z","timestamp":1696039326000},"page":"114-128","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["PD-L1 Blockade Improves Survival in Sepsis by Reversing Monocyte Dysfunction and Immune Disorder"],"prefix":"10.1007","volume":"47","author":[{"given":"Li","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiujing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8870-4587","authenticated-orcid":false,"given":"Shubin","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,30]]},"reference":[{"issue":"8","key":"1897_CR1","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1001\/jama.2016.0288","volume":"315","author":"CW Seymour","year":"2016","unstructured":"Seymour, C.W., V.X. 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