Dendritic cell-based cancer immunotherapy in the era of immune checkpoint inhibitors: From bench to bedside.

Abstract

Dendritic cells (DCs) can present tumoral antigens to T-cells and stimulate T-cell-mediated anti-tumoral immune responses. In addition to uptaking, processing, and presenting tumoral antigens to T-cells, co-stimulatory signals have to be established between DCs with T-cells to develop anti-tumoral immune responses. However, most of the tumor-infiltrated immune cells are immunosuppressive in the tumor microenvironment (TME), paving the way for immune evasion of tumor cells. This immunosuppressive TME has also been implicated in suppressing the DC-mediated anti-tumoral immune responses, as well. Various factors, i.e., immunoregulatory cells, metabolic factors, tumor-derived immunosuppressive factors, and inhibitory immune checkpoint molecules, have been implicated in developing the immunosuppressive TME. Herein, we aimed to review the biology of DCs in developing T-cell-mediated anti-tumoral immune responses, the significance of immunoregulatory cells in the TME, metabolic barriers contributing to DCs dysfunction in the TME, tumor-derived immunosuppressive factors, and inhibitory immune checkpoint molecules in DC-based cell therapy outcomes. With reviewing the ongoing clinical trials, we also proposed a novel therapeutic strategy to increase the efficacy of DC-based cell therapy. Indeed, the combination of DC-based cell therapy with monoclonal antibodies against novel immune checkpoint molecules can be a promising strategy to increase the response rate of patients with cancers.

• Authors: Farid Ghorbaninezhad, Zahra Asadzadeh, Javad Masoumi, Ahad Mokhtarzadeh, Tohid Kazemi, Leili Aghebati-Maleki, Siamak Sandoghchian Shotorbani, Mahdi Abdoli Shadbad, Amir Baghbanzadeh, Nima Hemmat, Mohammad Bakhshivand, Behzad Baradaran
• Journal: Life sciences (Life Sci) Vol. 297 Pg. 120466 (May 15 2022) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 35271882 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Immune Checkpoint Inhibitors

Topics

• Dendritic Cells
• Humans
• Immune Checkpoint Inhibitors (therapeutic use)
• Immunotherapy
• Neoplasms (metabolism)
• Tumor Microenvironment