PURPOSE: Interleukin (IL)-7 is a pleiotropic, non-redundant cytokine necessary for the development of B and T lymphocytes, in particular gamma delta T cell receptor-positive cell differentiation. The cytokine can function as a cofactor during myelopoiesis and the generation of cytotoxic T cells and natural killer cells, can activate monocytes/macrophages, and support the survival of mature T cells. Tumor-induced immune suppression has been well documented in lung cancer and other malignancies. Tumor-reactive T cells accumulate in lung cancer tissues but fail to respond, in part, because high proportions of non-small cell lung cancer (NSCLC) TIL are Treg cells. T regulatory cells have a significant impact on the host response to cancer and defining the pathways that attenuate Treg activities in cancer bearing hosts may enhance anti-tumor immune responses.
METHODS: We evaluate the mechanisms of anti-tumor response to systemic IL-7 treatment in the immune competent tumor bearing mice.
RESULTS: In this study we show that systemic administration of IL-7 to tumor bearing mice reduced the frequency and activity of Treg cells, enhanced T cell lytic activity against the parental tumor and decreased tumor burden. IL-7 treatment of tumor bearing mice significantly reduced the apoptosis rates in the T cell population compared to diluent tumor bearing mice. Transfer of Treg cells to IL-7 treated tumor bearing mice partially reversed the anti-tumor effects of IL-7.
CONCLUSION: We conclude that IL-7 can down regulate Treg cell activity and enhance anti-tumor responses in vivo.
CLINICAL IMPLICATIONS: The potent anti-tumor properties demonstrated in this model provide a strong rationale for additional evaluation of IL-7 regulation of tumor immunity and its use in immunotherapy for lung cancer.
DISCLOSURE: Seok Chul Yang, No Financial Disclosure Information; No Product/Research Disclosure Information