Phytohemagglutinin activates CD8 T cells in a model of the tumor microenvironment.

Abstract

Tumors often include a high proportion of immune modulatory cells and molecules that restrain the anti-cancer response. Activation of T cells to eliminate cancer cells within the immune suppressive tumor microenvironment (TME) remains a challenge. We have shown that C57BL/6J peritoneal cavity (PerC) cell culture models features of macrophage (Mθ)-rich TMEs as TCR ligation fails to activate T cells unless IFNγ is neutralized or iNOS is inhibited. We tested other forms of T cell activation and found phytohemagglutinin (PHA) distinctive in the ability to markedly expand CD8 T cells in the TME model. Neither IFNγ neutralization or iNOS inhibition were required for this response. IFNγR−/− PerC cells revealed that the PHA response is IFNg-dependent, yet this mitogen triggered less IFNγ production than TCR ligation. PHA-FITC staining revealed strong binding to Mfs and PerC cell addition to normally quiescent spleen (SP) cell cultures led to a marked increase in T cell expansion. The stimulatory capacity of PHA might reflect an ability to bind Mθs with CD8 T cells. Intriguingly, PerC Mf expression of the T cell inhibitory PD-L1 molecule was lower after PHA stimulation than that seen following TCR ligation. If PHA can increase CD8 T cell activation within the TME without increasing PD-L1 expression it might serve as an antitumor immune stimulant.