%0 Generic %A Eisel, David %A Das, Krishna %A Dickes, Elke %A König, Rainer %A Osen, Wolfram %A B. Eichmüller, Stefan %D 2019 %T Data_Sheet_1_Cognate Interaction With CD4+ T Cells Instructs Tumor-Associated Macrophages to Acquire M1-Like Phenotype.pdf %U 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 %R 10.3389/fimmu.2019.00219.s001 %2 https://frontiersin.figshare.com/ndownloader/files/14438132 %K tumor associated macrophages %K CD4+ T cells %K tumor microenvironment %K adoptive T cell transfer %K M2 macrophage %K T cell therapy %K CD206 %K iNOS %X

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+ 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+ 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+ 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 IAb−/− 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+ Th1/TAM axis in re-conditioning the immunosuppressive tumor microenvironment.

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