Dendritic Cell Subsets in Melanoma: Pathophysiology, Clinical Prognosis and Therapeutic Exploitation

Abstract

Evasion from immunity is a hallmark of cancer development. Dendritic cells (DCs) are strategic immune cells shaping anti-tumor immune responses, but tumor cells exploit DC versatility to subvert their functions. Unveiling the puzzling role of DCs in the control of tumor development and mechanisms of tumor-induced DC hijacking is critical to optimize current therapies and to design future efficient immunotherapies for melanoma. Dendritic cells, crucially positioned at the center of anti-tumor immunity, represent attractive targets to develop new therapeutic approaches. Harnessing the potencies of each DC subset to trigger appropriate immune responses while avoiding their subversion is a challenging yet promising step to achieve tumor immune control. This review focuses on advances regarding the diversity of DC subsets, their pathophysiology and impact on clinical outcome in melanoma patients. We provide insights into the regulation mechanisms of DCs by the tumor, and overview DC-based therapeutic developments for melanoma. Further insights into DCs’ diversity, features, networking, regulation and shaping by the tumor microenvironment will allow designing novel effective cancer therapies. The DCs deserve to be positioned in the current melanoma immunotherapeutic landscape. Recent discoveries strongly motivate exploitation of the exceptional potential of DCs to drive robust anti-tumor immunity, offering promising tracks for clinical successes.

Retrospective analysis of immune markers and BRAF status in melanoma patients: Implications for prognosis

“…However, modulation by tumour cells may render them non-functional. 6 A retrospective study investigating immune-related gene signature and prognosis in melanoma patients, utilizing sequenced DNA data from 453 samples, reported that prognosis was negatively correlated with activated dendritic cell infiltration. 7 Furthermore, BRAF mutations are independently associated with worse overall survival since these mutations may gain treatment…”

Differential Response of Human Dendritic Cells upon Stimulation with Encapsulated or Non-Encapsulated Isogenic Strains of Porphyromonas gingivalis

“…Recently, it has been proposed that pathological immune commitment begins with the first cells contacting and recognizing antigens [31][32][33]. Indeed, T-cell polarization could even be defined before antigen presentation when the microbial antigens induce a particular dendritic cell subset [31,[33][34][35].…”

“…Recently, it has been proposed that pathological immune commitment begins with the first cells contacting and recognizing antigens [31][32][33]. Indeed, T-cell polarization could even be defined before antigen presentation when the microbial antigens induce a particular dendritic cell subset [31,[33][34][35]. Certainly, dendritic cells could selectively acquire particular functional characteristics by recognizing capsular antigens of P. gingivalis and consequently, could influence the polarization and function of T lymphocytes and the nature of periodontal immunity [28,29].…”