Interleukin-12 in multimodal tumor therapies for induction of anti-tumor immunity

Abstract

Interleukin-12 (IL-12) can be used as an immunomodulator in cancer immunotherapy. And it has demonstrated enormous potential in inhibiting tumor growth and improving the tumor microenvironment (TME) by several preclinical models. However, some disappointing results have showed in the early clinical trials when IL-12 used as a single agent for systemic cancer therapy. Combination therapy is an effective way to significantly fulfill the great potential of IL-12 as an immunomodulator. Here, we discuss the effects of IL-12 combined with traditional methods (chemotherapy, radiotherapy and surgery), targeted therapy or immunotherapy in the preclinical and clinical studies. Moreover, we summarized the potential mechanism underlying the anti-tumor effect of IL-12 in the combination strategies. And we also discussed the delivery methods and tumor-targeted modification of IL-12 and outlines future prospects for IL-12 as an immunomodulator.

Keywords: Anti-tumor immunity; Combination therapy; Cytokine; IL-12.

Fig. 1

Summary of the physiological origin of IL-12 and its effects on downstream cells. The figure highlights that DCs, monocytes, macrophages and B cells will secrete IL-12 by stimulation. The major sensing cells are T cells and NK cells, and the major downstream effector molecule is IFN-γ. PAMPs/DAMPs: pathogen-associated molecular patterns/damage-associated molecular patterns

Fig. 2

The summary of IL-12 combined with other therapies. Potential combination strategies include traditional methods (chemotherapy, radiotherapy and surgery), targeted therapy and immunotherapy, and the potential mechanisms involved in the combined treatment induce synergistic effects, such as inhibition of angiogenesis, regulation of T cell infiltration, activation of Treg cells, and so on