Table 1 Cellular involvement in the tumour microenvironment
From: Enhanced nanoparticle delivery exploiting tumour-responsive formulations
Cell type | Role | References |
|---|---|---|
T-lymphocytes | CD8+: cytotoxic, good for prognosis CD4+: Th1—production of IL-2 and IFN-γ. Important for immune defense CD4+: Th2—tumour promoting, linked with inflammatory phenotype. Secrete inflammatory cytokines. Poor prognosis if in high number | Botchway et al. (2015), Brown et al. (2010), Burroughs et al. (2013) |
T-Regulatory (T-Reg) (lymphocyte) | Tumour promoting/ suppress tumour immunity Produce IL-10 and TGF-β allowing for enhanced cell growth Reduce cellular response to oxidative stress thereby contributing to the development of therapeutic resistance | Cathcart et al. (2015), Cheng et al. (2017), Coulter et al. (2013) |
Pericytes | Contractile cells Differentiate to stromal fibroblasts contributing to invasion/metastasis Provide structural support for blood vessels Decreased expression in TME allowing for increased metastasis | |
B-lymphocytes | Located in the invasive margin of the tumour and lymph nodes Involved in antitumour humoral immunity Release of cytokines and lymphotoxin activating pro-inflammatory pathways such as NF-κB | Deshayes et al. (2005), Dixit et al. (2015), Erler et al. (2006) |
Natural Killer (NK) | Innate cytotoxic lymphocytes Normally powerful cytotoxic activity but decreased presence in TME Influences a tumours ability to control tumour growth Important role in response to some targeted antibody therapies such as trastuzumab | |
Adipocytes | Aid recruitment of malignant cells due to presence of free fatty acids Act as “fuel” for cancer cells Assist in recruitment of macrophages, polarizing to M2 phenotype Produce IL-6, CCL2 and TNF-α | Gao et al. (2017), Gialeli et al. (2011), Haley and Frenkel (2008) |
Dendritic | Normal immune function—antigen presenting and processing cells Reduction in antigen presenting function Accumulation within tumour associated with increased patient survival | |
Tumour associated neutrophils (TAN) | Promote primary tumour growth Enhance angiogenesis Facilitate ECM degradation ROS and RNS production—DNA damage | Hatakeyama et al. (2007), Heitz et al. (2009), Heldin et al. (2004), Hill et al. (2008) |
Tumour associated macrophages (TAM) | Highly expressed in hypoxic, necrotic areas Associated with poor prognosis Involved in cell migration, invasion and metastasis and epithelial-mesenchymal transition Increase expression of MMP | Hua et al. (2018), Huanwen et al. (2009), Kanapathipillai et al. (2012) |
Myeloid derived suppressor cell(MDSC ) | Inhibitory immune cell Promote tumour growth Inhibit CD8+ T cell activity by increasing NOS2 expression | Hamdan and Zihlif (2014), Kato et al. (2013), Kobayashi et al. (2014) |
Vascular endothelial | Line the lumen of blood vessels essential for nutrient/oxygen supply In TME—abnormal in shape, chaotic branching promoting a leaky vasculature Stimulate inflammation and metastasis | |
Cancer associated fibroblasts (CAF) | Involved in organ fibrosis and cancer development Secrete chemo-attractants and growth factors—e.g. CXCL12 promotes growth and survival of malignant cells Enhances MMP production and neovascularization |