AUTHOR=Peng Wei , Chang Liang , Li Wenqiang , Liu Yanan , Zhang Min 

TITLE=OCT4 and SOX2 Specific Cytotoxic T Cells Exhibit Not Only Good Efficiency but Also Synergize PD-1 Inhibitor (Nivolumab) in Treating Breast Cancer Stem-Like Cells and Drug-Resistant Breast Cancer Mice

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.781093

DOI=10.3389/fonc.2022.781093

ISSN=2234-943X

ABSTRACT=<sec><title>Purpose</title><p>This study aimed to investigate the effect of OCT4&amp;SOX2 specific cytotoxic T lymphocytes (CTLs) plus programmed cell death protein-1 (PD-1) inhibitor (nivolumab) on treating breast cancer stem-like cells (BCSCs) <italic>in vitro</italic> and drug-resistance breast cancer (DRBC) mice <italic>in vivo</italic>.</p></sec><sec><title>Methods</title><p>In total, 160 breast cancer patients were enrolled following the immunofluorescence assay to detect tumor OCT4 and SOX2 expressions. CD154-activated B cells were co-cultured with CD8<sup>+</sup> T cells (from breast cancer patients) in the presence of OCT4&amp;SOX2 peptides, CMV pp65 peptides (negative control), and no peptides (normal control). MCF7-BCSCs were constructed by drug-resistance experiment and sphere-formation assay, then DRBC mice were constructed by planting MCF7-BCSCs. Subsequently, different doses of OCT4&amp;SOX2 CTLs and PD-1 inhibitor (nivolumab) were used to treat MCF7-BCSCs and DRBC mice.</p></sec><sec><title>Results</title><p>OCT4 and SOX2 correlated with poor differentiation, more advanced stage, and worse prognosis in breast cancer patients. <italic>In vitro</italic>, OCT4&amp;SOX2 CTLs with effector-target ratio (ETR) 5:1, 10:1 and 20:1 presented with increased cytotoxic activity compared to CMV pp65 CTLs with ETR 20:1 (negative control) and Control CTLs with ETR 20:1 (normal control) on killing MCF7-BCSCs. Besides, PD-1 inhibitor (nivolumab) improved the cytotoxic activity of OCT4&amp;SOX2 CTLs against MCF7-BCSCs in a dose-dependent manner. <italic>In vivo</italic>, OCT4&amp;SOX2 CTLs plus PD-1 inhibitor (nivolumab) decreased tumor volume and tumor weight while increased tumor apoptosis rate compared to OCT4&amp;SOX2 CTLs alone, PD-1 inhibitor (nivolumab) alone, and control.</p></sec><sec><title>Conclusion</title><p>OCT4&amp;SOX2 CTLs exhibit good efficiency and synergize PD-1 inhibitor (nivolumab) in treating BCSCs and DRBC.</p></sec>