Infiltration of Tumors Is Regulated by T cell-Intrinsic Nitric Oxide Synthesis

Nitric oxide (NO) is a signaling molecule produced by NO synthases (NOS1-3) to control processes such as neurotrans-mission, vascular permeability, and immune function. Although myeloid cell-derived NO has been shown to suppress T-cell responses, the role of NO synthesis in T cells themselves is not well understood. Here, we showed that significant amounts of NO were synthesized in human and murine CD8 thorn T cells following activation. Tumor growth was significantly accelerated in a T cell-specific, Nos2-null mouse model. Genetic deletion of Nos2 expression in murine T cells altered effector differentiation, reduced tumor infiltration, and inhibited recall responses and adoptive cell transfer function. These data show that endogenous NO production plays a critical role in T cell-mediated tumor immunity.

Automated summary

Nitric oxide (NO), produced by NO synthases (NOS1-3), regulates neurotransmission, vascular permeability, and immune function. While myeloid cell-derived NO suppresses T-cell responses, the role of NO synthesis in T cells themselves remains unclear. The study demonstrates that significant amounts of NO are synthesized in activated human and murine CD8 T cells. In a mouse model with T cell-specific deletion of Nos2 expression, tumor growth is accelerated. Genetic deletion of Nos2 in murine T cells alters effector differentiation, reduces tumor infiltration, and inhibits recall responses and adoptive cell transfer function. These findings highlight the critical role of endogenous NO production in T cell-mediated tumor immunity.