Tumour-associated macrophages and cancer
Section snippets
Macrophages, cancer and inflammation
Infiltrating immune cells are an abundant component of solid tumours [1, 2, 3]. The complex balance between pro-tumoural and anti-tumoural effects of immune cell infiltration is thought to create a chronic inflammatory microenvironment essential for tumour growth, progression and invasion [4, 5, 6•, 7, 8].
Macrophages are often found in the stromal compartment of solid tumours including breast, ovarian, pancreatic and hepatocellular carcinomas [9, 10, 11, 12]. Macrophages are part of the
Macrophage phenotypic characterisation
Phenotypic plasticity of macrophages allows them to adapt in response to environmental signals, which is key in innate immunity. Currently the macrophage phenotype is often simplified as either classical ‘M1’ or alternative ‘M2’ [14]. Although, it is now acknowledged that there is a spectrum of intermediate phenotypes that may also have different functional abilities [15, 16].
Classically activated macrophages or ‘M1’ like macrophages activate cells of the adaptive immune system and are
Tumour associated macrophage characterisation
A recent meta-analysis, taking into account recent exploitable data from 55 studies, summarised the current prognostic value of macrophage presence in cancer. Macrophage presence was associated with decreased survival in endometrial, prostate, urothelial bladder, ovary, gastric and oral carcinomas. The most striking effects were seen in breast cancer where the detrimental effects of TAM presence were found on clinical staging, vascular invasion, tumour volume, lymph node metastasis and HER-2
Inhibition of macrophage recruitment for anti-cancer therapy
Alternatively activated TAMs are an attractive target due to their range of tumour promoting roles and plasticity to reduce the surrounding inflammatory microenvironment and enhance anti-tumour activity [40, 8, 41•]. Current pre-clinical investigations into TAM abrogration as an anti-cancer strategy have shown promising results in murine models of breast and pancreatic cancer [29•, 42]. Clodronate was used for quite some time in many tumour studies to dissect the impact of macrophages on tumour
‘Re’-educating the TAM phenotype
Macrophages are highly abundant in the tumour microenvironment — this makes them a highly interesting clinical therapeutic target, as their genetic programmes are most likely more stable than those of malignant cells. In addition, to be able to adapt the macrophage phenotype in a temperospatial manner according to the therapeutic desirable response is highly attractive.
Pre-clinical studies have demonstrated that this approach is feasible. Data from our own group showed that by targeting the NF-κB
Challenges
Current understanding implicates macrophages in complex, diverse tumour-promoting roles within the tumour microenvironment. To mount an effective therapeutic offensive requires a well-founded understanding of macrophage phenotypic variation and interaction with tumour cells as well as identification of specific TAM markers. So far, re-programming of the tumour microenvironment to enhance anti-tumoural effects by targeting macrophages in early pre-clinical studies shows potential and the results
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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