Neutrophils suppress adaptive αβ T cells but not the innate γδ T cells and natural killer cells.

The presence of polymorphonuclear neutrophils (PMNs) in the tumor microenvironment is associated with lower survival rates for cancer patients. Presumably due to the immunosuppressive activity of neutrophils (also known as Myeloid-Derived Suppressor Cell (MDSC) activity). We investigated whether this MDSC activity shows any selectivity in suppressing specific lymphocyte subsets. Our data show that CD4+ and CD8+ T cells, both naive and memory fractions, are sensitive to PMN-MDSC activity. Similarly, regulatory T cells, believed to play an important immunosuppressive function themselves, were affected too. In contrast, the more innate-like γδ T cells and Natural Killer (NK) cells were left intact. Our data suggest that Chimeric Antigen Receptor (CAR)-NK and γδ CAR-T cell immunotherapy may be less susceptible to PMN-MDSC activity. Therefore, using such MDSC-resistant innate cells as cellular products may be of advantage over the common αβ CAR-T cell therapies. Additionally, further deciphering the exact mechanisms by which neutrophils suppress αβ T cells could lead to improved T cell immunotherapies.