Table 3.

A skew towards immunosuppression in the tumour microenvironment can drive resistance to immune checkpoint inhibitors.

Event	Impact on the Tumour Microenvironment
Increased AXL receptor tyrosine kinase (AXL) expression	Increases regulatory T cells, MDSCs and M2 macrophages [185]
Increased Wnt signalling	Decreases tumour infiltrating lymphocytes [185]
Loss of Phosphatase and tensin homolog (PTEN)	Induces vascular endothelial growth factor (VEGF) production and reduces T cell infiltration [176,185]
Loss of functional beta 2 microglobulin	Dysfunctional CD8+ T cells [175,188]
Hypoxia	Dysfunctional CD8+ T cells [184,187]
Upregulation of T cell immunoglobulin and mucin-domain containing-3 (Tim-3)	Dysfunctional T helper 1 (Th1) cells and reduced cytokine expression [189,190]
Reduced expression of absent in melanoma 2 (AIM2)	Decreases inflammation [181]
Reduced expression of poliovirus receptor-related immunoglobulin domain containing protein (PVRIG)	Dysfunctional CD8+ T cells [181]
Increased expression of mannosidase alpha class 2A member 1 (MAN2A1)	Altered Th1/T-helper 2 (Th2) axis towards Th2 expression [181]