The production of interferon-γ (IFNγ) is required for an effective, early (innate) immune response to tumour growth. A recent paper in Nature Medicine has identified that a novel subset of immune cells is able to produce this cytokine and kill tumour cells.

Dendritic cells (DCs) are an essential part of the immune system, as they help to activate lymphocytes in response to infection or tumour progression (an adaptive response), but part of the innate immune response to tumour development is mediated by natural killer (NK) cells. Recent studies indicate that there is substantial crosstalk between DCs and NK cells, so Taieb et al. studied the anti-tumour response in mice with B16F10 melanoma lung metastases. The authors had previously noted that imatinib mesylate (Gleevec) generates an anti-tumour response to these metastases that is mediated by NK cells. In this study, combining imatinib mesylate with interleukin-2 (IL-2) was found to increase this anti-tumour response. It also increased the number of DCs infiltrating the tumours, and most of these cells expressed B220, NK1.1 and other NK-cell markers. Consistent with these cells being a new subset of DCs, ∼50% also expressed major histocompatibilty complex (MHC) class II and could be detected in mice lacking lymphocytes and NK cells (mice lacking recombination-activating gene 2 (RAG2) and the common-cytokine receptor γ-chain (γc)).

When isolated from mice treated with imatinib mesylate and IL-2, these DCs mediated TRAIL (tumour-necrosis factor (TNF)-related apoptosis-inducing ligand)-dependent tumour-cell lysis. Expression of TRAIL is induced by IFNγ, and when stimulated with either tumour cells or imatinib mesylate and IL-2, these DCs produced large amounts of IFNγ, hence their name — IFN-producing killer DCs (IKDCs). Importantly, IKDCs controlled tumour-cell growth when transferred to mice lacking RAG2 and γc, indicating that IKDCs induce an effective anti-tumour response in vivo.

The authors conclude that IKDCs might be an important link between the innate and adaptive immune response to tumour growth.