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Objectives: Regulatory T (Treg) cells regulate immunity in autoimmune diseases and cancers. However, immunotherapies that target tumor‐infiltrating Treg cells often induce unwanted immune responses and tissue inflammation. Our research focussed on exploring the expression pattern of CD177 in tumor‐infiltrating Treg cells with the aim of identifying a potential target that can enhance immunotherapy effectiveness. Methods: Single‐cell RNA sequencing (scRNA‐seq) data and survival data were obtained from public databases. Twenty‐one colorectal cancer patient samples, including fresh tumor tissues, peritumoral tissues and peripheral blood mononuclear cells (PBMCs), were analysed using flow cytometry. The transendothelial activity of CD177+ Treg cells was substantiated using in vitro experiments. Results: ScRNA‐seq and flow cytometry results indicated that CD177 was exclusively expressed in intratumoral Treg cells. CD177+ Treg cells exhibited greater activation status and expressed elevated Treg cell canonical markers and immune checkpoint molecules than CD177− Treg cells. We further discovered that both intratumoral CD177+ Treg cells and CD177‐overexpressing induced Treg (iTreg) cells had lower levels of PD‐1 than their CD177− counterparts. Moreover, CD177 overexpression significantly enhanced the transendothelial migration of Treg cells in vitro. Conclusions: These results demonstrated that Treg cells with higher CD177 levels exhibited an enhanced activation status and transendothelial migration capacity. Our findings suggest that CD177 may serve as an immunotherapeutic target and that overexpression of CD177 may improve the efficacy of chimeric antigen receptor T (CAR‐T) cell therapy. [ABSTRACT FROM AUTHOR]

Objectives: Extracorporeal membrane oxygenation (ECMO) plays an important role in providing temporary life support for patients with severe cardiac or pulmonary failure, but requires strict anticoagulation and monitoring. This network meta‐analysis systematically explored the most effective anticoagulation and monitoring strategies for patients receiving ECMO. Methods: MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched up to January 31, 2023, for studies comparing unfractionated heparin (UFH), argatroban (Arg), bivalirudin (Biv), and/or nafamostat mesylate (NM) in patients receiving ECMO. The primary outcomes included device‐related thrombosis, patient‐related thrombosis, and major bleeding events. The secondary outcomes included ECMO survival, ECMO duration, and in‐hospital mortality. Results: A total of 2522 patients from 23 trials were included in the study. Biv was associated with a decreased risk of device‐related thrombosis (odd ratio [OR] 0.51, 95% confidence interval [CI]: 0.33–0.84) compared with UFH, whereas NM (OR 2.2, 95% CI: 0.24–65.0) and Arg (OR 0.92, 95% CI: 0.43–2.0) did not reduce the risk of device‐related thrombosis compared with UFH. Biv was superior to Arg in decreasing the risk of device‐related thrombosis (OR 0.14, 95% CI: 0.03–0.51). Biv reduced the risk of patient‐related thrombosis compared with UFH (OR 0.44, 95% CI: 0.18–0.85); NM (OR 0.65, 95% CI: 0.14–3.3) and Arg (OR 3.1, 95% CI: 0.94–12.0) did not decrease risk of patient‐related thrombosis compared with UFH. No significant difference was observed in the risk of major bleeding between three alternatives and UFH: Biv (OR 0.54, 95% CI: 0.23–1.3), Arg (OR 1.3, 95% CI: 0.34–5.8), and NM (OR 0.60, 95% CI: 0.13–2.6). NM showed a reduced risk of in‐hospital mortality compared with UFH (OR 0.27, 95% CI: 0.091–0.77), whereas Arg (OR 0.43, 95% CI: 0.15–1.2) and Biv (OR 0.75, 95% CI: 0.52–1.1) did not decrease risk of in‐hospital mortality. Conclusions: Compared with UFH and Arg, Biv reduces the risk of thrombosis and appears to be a better choice for patients requiring ECMO. NM was associated with a reduced risk of in‐hospital mortality. [ABSTRACT FROM AUTHOR]

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