IFN-Alpha-Mediated Differentiation of Dendritic Cells for Cancer Immunotherapy: Advances and Perspectives

Abstract

The past decade has seen tremendous developments in novel cancer therapies through targeting immune-checkpoint molecules. However, since increasing the presentation of tumor antigens remains one of the major issues for eliciting a strong antitumor immune response, dendritic cells (DC) still hold a great potential for the development of cancer immunotherapy. A considerable body of evidence clearly demonstrates the importance of the interactions of type I IFN with the immune system for the generation of a durable antitumor response through its effects on DC. Actually, highly active DC can be rapidly generated from blood monocytes in vitro in the presence of IFN-α (IFN-DC), suitable for therapeutic vaccination of cancer patients. Here we review how type I IFN can promote the ex vivo differentiation of human DC and orientate DC functions towards the priming and expansion of protective antitumor immune responses. New epigenetic elements of control on activation of the type I IFN signal will be highlighted. We also review a few clinical trials exploiting IFN-DC in cancer vaccination and discuss how IFN-DC could be exploited for the design of effective strategies of cancer immunotherapy as a monotherapy or in combination with immune-checkpoint inhibitors or immunomodulatory drugs.

Induced dendritic cells co-expressing GM-CSF/IFN-α/tWT1 priming T and B cells and automated manufacturing to boost GvL

“…It was shown pre-clinically that monocytes modified to express IFN-α reprogrammed the tumor microenvironment and inhibited leukemia in a mouse model. 31 We and others 32 have shown that IFN-α promotes the ex vivo differentiation of mature DCs with migratory capabilities, and therefore, IFN-DCs are actively being exploited in clinical trials for cancer vaccination.…”

TIM-1 inhibits cancer cell proliferation by regulating IFIT2 and is correlated with prognosis in bladder cancer

“…IFN-α is well known for its key roles in antiviral immune responses. Recently, the intratumoral expression levels of IFN-α and IFIT genes were reported to be associated with improved patient outcomes in multiple cohorts of cancer cases, and new anticancer immunotherapies based on recombinant IFN-α have been recently developed [37][38][39]. Therefore, our ndings further con rmed TIM-1 as a potential biomarker of BC that could regulate IFIT2 and intratumoral IFN-α, playing a dual antitumor role due to the important role of the cytokine IFN-α in tumor immunotherapy.…”

Emerging Strategies of Engineering and Tracking Dendritic Cells for Cancer Immunotherapy

“…59 Surprisingly, in the absence of maturation factors, fully functional IFN-DCs can be differentiated after 3 days of culture, thus facilitating clinical applications. 58 However, upon inoculation with different antigens, the advantages of IL-4 MoDCs and IFN-DCs differ. In the context of DC vaccination with synthetic long peptide (SLP), the use of IFN-DCs is superior to IL-4 MoDCs, whereas IL-4 MoDCs are more suitable for vaccination with antigens from apoptotic cellderived blebs.…”