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An independent study reported that cultures of stimulated splenic mouse mononuclear cells treated with nicotine showed reduced generation of CTLA-4+ CD4+ T cells and decreased production of INF and IL-2 compared with control cultures without nicotine treatment in vitro ( Interestingly, the importance of CTLA-4 in the context of cancer and nicotine exposure can be observed indirectly in a tumor model ( 4.2.4 Nicotine and other immune checkpoints Nicotine can promote CD47 expression in human non-small cell lung cancer cell lines ( in vitro , including stem cell-like characteristics, such as increased levels of CD44, SOX2, and NANOG and enhanced sphere formation efficiency ( In vitro studies suggested that activation of the nAChR/STAT3/CD47 axis in tumor cells reduced phagocytosis by monocytes and decreased TNF levels

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