Monocyte programming by cancer therapy

Abstract

Monocytes in peripheral blood circulation are the precursor of essential cells that control tumor progression, that include tumor-associated macrophages (TAMs), dendritic cells (DCs) and myeloid-derive suppressor cells (MDSC). Monocytes-derived cells orchestrate immune reactions in tumor microenvironment that control disease outcome and efficiency of cancer therapy. Four major types of anti-cancer therapy, surgery, radiotherapy, chemotherapy, and most recent immunotherapy, affect tumor-associated macrophage (TAM) polarization and functions. TAMs can also decrease the efficiency of therapy in a tumor-specific way. Monocytes is a major source of TAMs, and are recruited to tumor mass from the blood circulation. However, the mechanisms of monocyte programming in circulation by different therapeutic onsets are only emerging. In our review, we present the state-of-the art about the effects of anti-cancer therapy on monocyte progenitors and their dedifferentiation, on the content of monocyte subpopulations and their transcriptional programs in the circulation, on their recruitment into tumor mass and their potential to give origin for TAMs in tumor-specific microenvironment. We have also summarized very limited available knowledge about genetics that can affect monocyte interaction with cancer therapy, and highlighted the perspectives for the therapeutic targeting of circulating monocytes in cancer patients. We summarized the knowledge about the mediators that affect monocytes fate in all four types of therapies, and we highlighted the perspectives for targeting monocytes to develop combined and minimally invasive anti-cancer therapeutic approaches.

Keywords: anti-cancer treatment; chemotherapy; genotype; immunotherapy; monocyte; radiotherapy; surgery.

Figure 1

Interaction of four major types of cancer therapy with monocyte programming. Effects of surgery (A), radiotherapy (B), chemotherapy (C) and immunotherapy (D) on the differentiation of the monocyte progenitors in bone marrow, monocyte amounts and content in the circulation, recruitment to tumor and differentiation into TAMs are separately presented. Soluble mediators of the therapy effects are listed in the grey arrows. GM-CSF- Granulocyte-macrophage colony-stimulating factor, M-CSF - Macrophage colony-stimulating factor, CCL2 - Monocyte chemoattractant protein 1 (MCP1), IL1 – Interleukin1, IL3 – Interleukin 3, IL4 – Interleukin 4, IL6 – Interleukin 6, IL10 – Interleukin 10, MCP5 - Monocyte chemotactic protein 5 (CCL12), MIFα- Macrophage Migration Inhibitory Factor α, ROS - , VEGF - Vascular endothelial growth factor α, INFy – Interferon γ, PGE2 - Prostaglandin E, IDO - indoleamine 2,3-dioxygenase, TNFa - tumor necrosis factor α, S100A9 - S100 calcium-binding protein A9.

Figure 2

Chromosomal localisation of SNPs associated with the monocytes’ involvement in the cancer therapy effects. Figure created in biorender (http://biorender.io).