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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)
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
Cox et al. (2014), Dai et al. (2011)
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
Fais et al. (2014), Feuerecker et al. (2015)
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
Hamdan and Zihlif (2014), Hanahan and Weinberg (2011)
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
Kumar et al. (2013), Li et al. (2013)
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
Li et al. (2004, 2016), Liu et al. (2013)