Post-transplant malignancy: Focusing on virus-associated etiologies, pathogenesis, evidence-based management algorithms, present status of adoptive immunotherapy and future directions

Table 5 Viruses and their specific carcinogenic mechanisms

Virus	Carcinogenic mechanisms
EBV	EBV-infected cells generates more interleukin-6, which promotes the proliferation of B-cells, and interleukin-10, an immunosuppressive cytokine that promotes tumour development
HPV	E6 and E7 proteins expressed by HPV suppress p53-mediated apoptosis and increase malignant growth in infected cells
HHV8	Viral proteins encoded by HHV8 inhibit the activation of pro-caspase-8, promotes Ras-PI3K-Akt survival pathway and enhances antiapoptotic Bcl-2 (B-cell lymphoma 2) expression, thereby inhibiting apoptosis and promoting uncontrolled proliferation of infected and endothelial cells
HBV	HBx proteins produced by virus activate the Ras-PI3K-Akt survival pathway and change EGFR signalling. In addition, it modifies the transcriptional activity of c-Myc, c-Fos, and c-Jun and promotes the expression of angiogenic factors, including VEGF and angiopoietin-1. Consequently, this stimulates proliferation and angiogenesis
HCV	Virus-produced non-structural proteins (NS3 and NS5A) promote the Ras-PI3K-Akt survival pathway. NS5A also modulates the signalling mediated by. Consequently, this stimulates proliferation and angiogenesis

EBV: Epstein–Barr virus; HPV: Human papilloma virus; HHV8: Human herpes virus 8; HBV: Hepatitis B virus; HCV: Hepatitis C virus; EGFR: Epidermal growth factor receptor; VEGF: Vascular endothelial growth factor.