Tumor-Associated Macrophage Status in Cancer Treatment

Abstract

Tumor-associated macrophages (TAMs) represent the most abundant innate immune cells in tumors. TAMs, exhibiting anti-inflammatory phenotype, are key players in cancer progression, metastasis and resistance to therapy. A high TAM infiltration is generally associated with poor prognosis, but macrophages are highly plastic cells that can adopt either proinflammatory/antitumor or anti-inflammatory/protumor features in response to tumor microenvironment stimuli. In the context of cancer therapy, many anticancer therapeutics, apart from their direct effect on tumor cells, display different effects on TAM activation status and density. In this review, we aim to evaluate the indirect effects of anticancer therapies in the modulation of TAM phenotypes and pro/antitumor activity.

Novel Photosensitizer β-Mannose-Conjugated Chlorin e6 as a Potent Anticancer Agent for Human Glioblastoma U251 Cells

“…The other different molecular region of β-M-Ce6 compared with TS is a mannose residue. This approach was based on the high expression of the mannose receptor in TAMs [ 17 , 19 , 20 , 25 ]. TAMs influence progression, metastasis, and tumor recurrence, which originate mainly from circulating monocytes, but resident macrophages also develop in a tumor [ 26 , 27 ].…”

“…Glucose conjugation is based on Warburg effects whereby cancer cells in general consume more glucose than normal cells [ 15 , 16 ]. Another strategy to enhance the cancer specificity of a photosensitizer is targeting tumor-associated macrophages (TAMs), a class of immune cells that exist in high numbers in the solid tumor microenvironment [ 17 , 18 , 19 ]. TAMs with high expression of mannose receptor are pro-tumorigenic cells that negatively affect therapy responsiveness [ 17 , 18 , 19 , 20 ].…”

“…Another strategy to enhance the cancer specificity of a photosensitizer is targeting tumor-associated macrophages (TAMs), a class of immune cells that exist in high numbers in the solid tumor microenvironment [ 17 , 18 , 19 ]. TAMs with high expression of mannose receptor are pro-tumorigenic cells that negatively affect therapy responsiveness [ 17 , 18 , 19 , 20 ]. In this context, we also developed a mannose-conjugated chlorin derivative, H2TFPC-SMan, 5,10,15,20-tetrakis (4-(α-d-mannopyranosylthio)-2,3,5,6-tetrafluorophenyl)-2,3-(methano ( N -methyl) iminomethano) chlorin, which shows significant anti-cancer effects and accumulation in M2-polarized macrophages [ 21 , 22 ].…”

Simultaneous Tumor and Stroma Targeting by Oncolytic Viruses

“…In solid tumors, half of the tumor mass is represented by types of macrophages known as TAMs, which polarize into the pro-tumoral and anti-inflammatory M2 phenotype. The described recruitment and polarization are promoted by the tumor and immune cell secreted cytokines, growth factors and metabolites such as VEGF, colony stimulating factor-1 (CSF-1) and chemokine CCL2 [54]. TAMs can be distinguished from the M1 phenotype based on their specific markers, including CD163, CD204, and CD200R, and their upregulated genes, such as arginase-1 and macrophage mannose receptor [55].…”

“…Targeting of the highly abundant TAM population and their interactions with the tumor cells and other stromal components may help to reduce primary tumor growth, metastases, and recurrence. Multiple therapeutic approaches to reduce the pro-tumoral effects of TAMs have been reviewed by Portella and colleagues, including TAM depletion, reduction in macrophage recruitment, or modulation of the pro-tumoral M1 to M2 macrophages polarization [54]. The oncolytic effect of OVs is shown to be closely related to the macrophage phenotype present in the tumor stroma.…”