Differential Tumor Surveillance by Natural Killer (Nk) and Nkt Cells

TLDR

Investigate host tumor surveillance in six mouse models to determine how endogenous IL‑12 influences innate immune efficacy. Use gene‑targeted and lymphocyte subset‑depleted mice to assess the relative contributions of NK and NKT cells to protection against tumor initiation and metastasis. NK cells mediate tumor rejection and metastasis protection in IL‑12–independent models, while NKT cells contribute only when IL‑12 is required, as demonstrated by TCR Jα281 mice in spontaneous methylcholanthrene‑induced tumors—providing the first evidence of NKT antitumor activity without exogenous stimulators.

Abstract

Natural tumor surveillance capabilities of the host were investigated in six different mouse tumor models where endogenous interleukin (IL)-12 does or does not dictate the efficiency of the innate immune response. Gene-targeted and lymphocyte subset-depleted mice were used to establish the relative importance of natural killer (NK) and NK1.1(+) T (NKT) cells in protection from tumor initiation and metastasis. In the models examined, CD3(-) NK cells were responsible for tumor rejection and protection from metastasis in models where control of major histocompatibility complex class I-deficient tumors was independent of IL-12. A protective role for NKT cells was only observed when tumor rejection required endogenous IL-12 activity. In particular, T cell receptor Jalpha281 gene-targeted mice confirmed a critical function for NKT cells in protection from spontaneous tumors initiated by the chemical carcinogen, methylcholanthrene. This is the first description of an antitumor function for NKT cells in the absence of exogenously administered potent stimulators such as IL-12 or alpha-galactosylceramide.