Early activation and interferon-γ production of tumor-infiltrating mature CD27high natural killer cells

Natural killer (NK) cells are known to be critically involved in the control of tumors through their direct cytotoxic function, but have also been proposed as an initial source of interferon (IFN)-gamma that primes subsequent adaptive tumor-specific immune responses. Although mounting evidence supports the importance of NK cells in antitumor immune responses, the immunological characteristics of NK cells infiltrating the tumor microenvironment and the mechanisms that regulate this process remain unclear. In the present study, we found that NK cells infiltrate early developing MCA205 tumors, and further showed that mature CD27(high) NK cells were the predominant subpopulation of NK cells accumulating in the tumor microenvironment. The tumor-infiltrating NK cells displayed an activated cell surface phenotype and provided an early source of IFN-gamma. Importantly, we also found that host IFN-gamma was critical for NK cell infiltration into the local tumor site and that the tumor-infiltrating NK cells mainly suppressed tumor growth via the IFN-gamma pathway. This work implicates the importance of IFN-gamma as a positive regulatory factor for NK cell recruitment into the tumor microenvironment and an effective antitumor immune effector response. (Cancer Sci 2011; 102: 1967-1971)