Data_Sheet_1_Cognate Interaction With CD4+ T Cells Instructs Tumor-Associated Macrophages to Acquire M1-Like Phenotype.pdf David Eisel Krishna Das Elke Dickes Rainer König Wolfram Osen Stefan B. Eichmüller 10.3389/fimmu.2019.00219.s001 https://frontiersin.figshare.com/articles/dataset/Data_Sheet_1_Cognate_Interaction_With_CD4_T_Cells_Instructs_Tumor-Associated_Macrophages_to_Acquire_M1-Like_Phenotype_pdf/7755347 <p>The immunosuppressive tumor microenvironment (TME) established by tumor cells, stromal cells and inhibitory immune cells counteracts the function of tumor reactive T cells. Tumor associated macrophages (TAMs) showing functional plasticity contribute to this process as so called M2-like macrophages can suppress the function of effector T cells and promote their differentiation into regulatory T cells (Tregs). Furthermore, tumor antigen specific CD4<sup>+</sup> T effector cells can essentially sustain anti-tumoral immune responses as shown for various tumor entities, thus suggesting that cognate interaction between tumor antigen-specific CD4<sup>+</sup> Th1 cells and TAMs might shift the intra-tumoral M1/M2 ratio toward M1. This study demonstrates repolarization of M2-like PECs upon MHC II-restricted interaction with tumor specific CD4<sup>+</sup> Th1 cells in vitro as shown by extensive gene and protein expression analyses. Moreover, adoptive transfer of OVA-specific OT-II cells into C57BL/6 mice bearing OVA expressing IA<sup>b−/−</sup> tumors resulted in increased accumulation of M1-like TAMs with enhanced M1 associated gene and protein expression profiles. Thus, this paper highlights a so far underestimated function of the CD4<sup>+</sup> Th1/TAM axis in re-conditioning the immunosuppressive tumor microenvironment.</p> 2019-02-22 04:14:15 tumor associated macrophages CD4+ T cells tumor microenvironment adoptive T cell transfer M2 macrophage T cell therapy CD206 iNOS