Conventional type 1 dendritic cells (cDC1) as cancer therapeutics: challenges and opportunities

ABSTRACT

Introduction

The use of dendritic cell (DC)-based cancer vaccines over three decades has shown them to be a safe therapeutic approach against a range of hematological and solid malignancies. However, underwhelming and inconsistent results from clinical trials have seen them move in and out of favor. The limitations of ex vivo generated monocyte-derived DC (MoDC) in these therapies provide a pointed explanation for the varying and somewhat disappointing clinical outcomes. The identification of a specialized role for the rare conventional type 1 dendritic cell (cDC1) subset in orchestrating tumor immunity via the initiation of CD8⁺ T cell responses has led to a new concept of targeting cDC1 as a therapeutic option to address the unmet need of enhancing the immune response in cancer patients.

Areas Covered

This article reviews several current challenges and key opportunities associated with the development and use of next generation cDC1 cancer vaccines.

Expert Opinion

Manipulation of cDC1 quantity and quality holds enormous potential to improve tumor immunogenicity, as already demonstrated in preclinical models. New technologies are rapidly advancing the understanding of cDC1 in human cancer patients and facilitating the generation of these extremely rare cells in vitro, providing feasible new approaches toward clinical translation.

KEYWORDS:

• Cancer immunotherapy
• dendritic cells
• vaccines
• cell therapies
• cord blood

Article highlights

• The specialized role of cDC1 in orchestrating tumor immunity offers a potential pathway to overcome the limitations observed to date with the use of DC-derived cancer vaccines.

• Absolute numbers, dysregulation of patient-derived DCs, and time-to-access remain key challenges in the development of cDC1-based cancer vaccines.

• Next generation cDC1 therapeutics can be expected to deliver significant outcomes for many cancer patients in the future.

Declaration of Interests

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper is funded by the Mater Foundation, Brisbane, Australia.