IL-12 and the Antitumor Response: The Good, the Bad, and the Unknown

IL-12 is a proinflammatory cytokine secreted by antigen-presenting cells. It promotes the differentiation of cytotoxic T cells, which makes it a strong candidate to boost the antitumor immune response in cancer patients. While its first use in humans faced severe toxicity, more recent approaches have been taken to limit toxicity while retaining its biologic function. These strategies, summarized in this review, include systemic and local delivery of IL-12 and demonstrated promising results in murine tumor models. However, their translation in cancer patients was met with limited efficacy. Recent evidence indicates that exposure to IL-12 results in the expression of immunoregulatory molecules by T cells, suggesting the existence of a negative feedback loop that might impair the antitumor immune response. Therefore, a more thorough understanding of the biology of IL-12 in the context of cancer is crucial to advance the design of novel clinical trials. This approach can lead to improved therapy regimens and promising results in the future.