Figure 5: Role of TNF-TNFR2 in the progression of breast cancer and the potential role of TNF antagonists in competing with TNFR2 by mopping up excess soluble TNF and binding on the membrane-bound TNF. (a) TNFR2 is expressed on immune cells and tumour cells in cancer microenvironment. Instead of apoptosis, TNFR2 induces malignant transformation and tumour proliferation by sTNF that activates TNFR2 to enhance Tregs, cancer cells, and MDSC. Therefore, TNFR2 is implicated in enhancing tumour progression either by maintaining cancer microenvironment (immune responses) and enhancing cancer immune evasion, or by inducing cancer cells survival and proliferation [116]. TNFR2 was implicated in promoting the progression of breast cancer via stimulation of AKT signalling pathway which protects against DNA damage and, consequently, enhances proliferation, CAF induction, angiogenesis, and carcinogenesis. Further, a positive association had been reported between TNFR2 expression and its prognosis in terms of size of tumour, higher pathological grade, advanced clinical stage, and dampened doxorubicin resistance [95, 102]. (b) We hypothesized that TNF antagonists would modify breast cancer cells’ signalling effects that lead to division, migration, differentiation, or death by assessing their expression markers and secreted cytokines.