Reprogramming of myeloid cells of the tumor microenvironment – a new approach in the immunotherapy of malignant neoplasms

Abstract

Modern therapy of a cancer patient, especially immunotherapy, must take into account and overcome the immunosuppression created inside the tumor and, in general, in the body affected by a malignant neoplasm. Without overcoming immunosuppression, it is impossible to achieve effective elimination of malignant cells by the forces of immune mechanisms.

The immunosuppressive properties of the tumor microenvironment are formed by both malignant and non-malignant cells and the substances they produce. Myeloid cells, tumor-associated macrophages, intratumoral dendritic cells, and myeloid suppressors attracted by the tumor, play a significant role in creating an immunosuppressive milieu inside the tumor. These cells produce soluble inhibitors of immune responses such as IDO, TGF-β, IL-10, prostaglandins, and also exhibit on their surface molecules that have the ability to suppress immune cells, in particular, PD-L1/2 molecules that cause functional paralysis of T cells or even their death.

In this literature review, we consider the immunosuppressive properties of macrophages, dendritic cells, and other tumor-associated myeloid cells aiming to overcome this mechanism of immunosuppression during the treatment of cancer patients. We present an analysis of the literature and our own results of the correction of immunity by targeting of tumor myeloid cells. The presented data suggest that a correction of the tumor myeloid cells’ properties is new effective approach in the immunotherapy of malignant neoplasms.

Keywords:malignant neoplasm; microenvironment; immunosuppression; myeloid cells; reprogramming; immunotherapy

For citation: Ataullakhanov R.I., Ushakova E.I., Al Khudhur S.А., Pichugin A.V., Lebedeva E.S. Reprogramming of myeloid cells of the tumor microenvironment – a new approach in the immunotherapy of malignant neoplasms. Immunologiya. 2022; 43 (4): 375–88. DOI: https://doi.org/10.33029/0206-4952-2022-43-4-375-388 (in Russian)

Funding. The study was supported by a grant from the Russian Science Foundation (project No. 20-15-00391).

Conflict of interests. The authors declare no conflict of interests.

Authors’ contribution. Concept, literature analysis, article writing – Ataullakhanov R.I.; literature analysis, article writing and editing – Ushakova E.I.; literature analysis, article writing – Al Khudur S.A.; literature analysis, article editing – Pichugin A.V.; literature analysis, article editing – Lebedeva E.S.

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