Functional Role of Dendritic Cell Subsets in Cancer Progression and Clinical Implications.

Annalisa Del Prete,Francesca Sozio,Silvano Sozzani,Mattia Laffranchi,Valentina Salvi,Angela Gismondi,Laura Tiberio,Daniela Bosisio,Tiziana Schioppa,Ilaria Barbazza

doi:10.3390/ijms21113930

Abstract

Dendritic cells (DCs) constitute a complex network of cell subsets with common functions but also with many divergent aspects. All dendritic cell subsets share the ability to prime T cell response and to undergo a complex trafficking program related to their stage of maturation and function. For these reasons, dendritic cells are implicated in a large variety of both protective and detrimental immune responses, including a crucial role in promoting anti-tumor responses. Although cDC1s are the most potent subset in tumor antigen cross-presentation, they are not sufficient to induce full-strength anti-tumor cytotoxic T cell response and need close interaction and cooperativity with the other dendritic cell subsets, namely cDC2s and pDCs. This review will take into consideration different aspects of DC biology, including the functional role of dendritic cell subsets in both fostering and suppressing tumor growth, the mechanisms underlying their recruitment into the tumor microenvironment, as well as the prognostic value and the potentiality of dendritic cell therapeutic targeting. Understanding the specificity of dendritic cell subsets will allow to gain insights on role of these cells in pathological conditions and to design new selective promising therapeutic approaches.

Highlights

Dendritic cells (DCs) represent the bridge between innate and adaptive immune responses [1]
This review will take into consideration different aspects of DC biology, including the functional role of dendritic cell subsets in both fostering and suppressing tumor growth, the mechanisms underlying their recruitment into the tumor microenvironment, as well as the prognostic value and the potentiality of dendritic cell therapeutic targeting
Based on the repertoire of transcription factors that control their development, conventional DCs (cDCs) can be further divided into cDC1s, which are under the control of IRF8, ID2, and BATF3, and cDC2s, which develop under the control of IRF4, ID2, ZEB, and Notch2/KLF4 [8]

Summary

Introduction

Dendritic cells (DCs) represent the bridge between innate and adaptive immune responses [1]. They are specialized in antigen recognition and presentation and play a central role in the initiation of antigen-specific immunity as well as tolerance [2]. Different DC subsets play specific roles in antitumor immunity through the expression of costimulatory molecules and inflammatory cytokines and have the ability to activate specific T cell subsets [19]. DCs can favor the formation of a tumor-promoting local microenvironment by secreting anti-inflammatory cytokines and expressing immune checkpoint molecules able to restrain T cell response [20]. We will discuss: (i) the specific role of DC subsets in fostering or suppressing tumor growth; (ii) the molecules responsible for the recruitment of DC subsets into tumor microenvironment (TME); (iii) the prognostic value of DC subsets in TME, and (iv) the potential therapeutic implications of targeting specific DC subsets in cancer immunotherapy

Anti-Tumor Activity of DC Subsets

Regulation of DC Subsets Migration in TME

Prognostic Value of DC Subsets in TME

Targeting DC Subsets to Improve Cancer Immunotherapy

Findings

Conclusions