Granzymes are essential for natural killer cell-mediated and perf-facilitated tumor control

Essential for Perforin-Mediated Tumor Cutting Edge: Granzymes A and B Are Not

An Essential Role for Tumor Necrosis Factor in Natural Killer Cell–mediated Tumor Rejection in the Peritoneum

Natural killer (NK) cells are thought to provide the first line of defence against tumors, particularly major histocompatibility complex (MHC) class I- variants. We have confirmed in C57BL/6 (B6) mice lacking perforin that peritoneal growth of MHC class I- RMA-S tumor cells in unprimed mice is controlled by perforin-dependent cytotoxicity mediated by CD3(-) NK1.1(+) cells. Furthermore, we demon...

Stat5b Is Essential for Natural Killer Cell–mediated Proliferation and Cytolytic Activity

We have analyzed the immune system in Stat5-deficient mice. Although Stat5a-/- splenocytes have a partial defect in anti-CD3-induced proliferation that can be overcome by high dose interleukin (IL)-2, we now demonstrate that defective proliferation in Stat5b-/- splenocytes cannot be corrected by this treatment. Interestingly, this finding may be at least partially explained by diminished expres...

Natural Killer Cell-Mediated Shedding of ULBP2

UL16 binding proteins (ULBPs) are a family of cell surface proteins that are present in transformed and stressed cells and ligands for NKG2D. Soluble NKG2D ligands have been found in sera from cancer patients with their protein concentrations correlated with poor cancer prognosis. Here we show, for the first time, that human tumor cells lost their surface expression of ULBP2, but not ULBP1 and ...

The Critical Role of the Tumor Microenvironment in Shaping Natural Killer Cell-Mediated Anti-Tumor Immunity

Considerable evidence has been gathered over the last 10 years showing that the tumor microenvironment (TME) is not simply a passive recipient of immune cells, but an active participant in the establishment of immunosuppressive conditions. It is now well documented that hypoxia, within the TME, affects the functions of immune effectors including natural killer (NK) cells by multiple overlapping...