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Cognate interaction with CD4+ T cells instructs tumor-associated macrophages to acquire M1-like phenotype

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 c...

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Main Authors: Eisel, David (Author) , Das, Krishna (Author) , Dickes, Elke (Author) , König, Rainer (Author) , Osen, Wolfram (Author) , Eichmüller, Stefan B. (Author)
Format: Article (Journal)
Language:English
Published: 22 February 2019
In: Frontiers in immunology
Year: 2019, Volume: 10
ISSN:1664-3224
DOI:10.3389/fimmu.2019.00219
Online Access:Verlag, Volltext: https://doi.org/10.3389/fimmu.2019.00219
Verlag, Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2019.00219/full
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Author Notes:David Eisel, Krishna Das, Elke Dickes, Rainer König, Wolfram Osen and Stefan B. Eichmüller

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520 |a 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+ T cells and TAMs might shift the intra-tumoral M1/M2 ratio towards M1. This study demonstrates repolarization of M2 like PECs upon MHC II-restricted interaction with tumor specific CD4+ T 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+ T cell / TAM axis in re-conditioning the immunosuppressive tumor microenvironment. 
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