Transforming growth factor-β signalling in tumour resistance to the anti-PD-(L)1 therapy: Updated

Low frequency of durable responses in patients treated with immune checkpoint inhibitors (ICIs) demands for taking complementary strategies in order to boost immune responses against cancer. Transforming growth factor-beta (TGF-beta) is a multi-tasking cytokine that is frequently expressed in tumours and acts as a critical promoter of tumour hallmarks. TGF-beta promotes an immunosuppressive tumour microenvironment (TME) and defines a bypass mechanism to the ICI therapy. A number of cells within the stroma of tumour are influenced from TGF-beta activity. There is also evidence of a relation between TGF-beta with programmed death-ligand 1 (PD-L1) expression within TME, and it influences the efficacy of anti-programmed death-1 receptor (PD-1) or anti-PD-L1 therapy. Combination of TGF-beta inhibitors with anti-PD(L)1 has come to the promising outcomes, and clinical trials are under way in order to use agents with bifunctional capacity and fusion proteins for bonding TGF-beta traps with anti-PD-L1 antibodies aiming at reinvigorating immune responses and promoting persistent responses against advanced stage cancers, especially tumours with immunologically cold ecosystem.

Automated summary

The low frequency of durable responses in patients treated with immune checkpoint inhibitors (ICIs) requires additional strategies to enhance immune responses against cancer. Transforming growth factor-beta (TGF-beta) is a cytokine often expressed in tumors and promotes an immunosuppressive tumor microenvironment (TME). TGF-beta also influences the efficacy of anti-PD-1/PD-L1 therapy. Combining TGF-beta inhibitors with anti-PD(L)1 has shown promising results, and clinical trials are currently underway to investigate the use of agents with bifunctional capacity and fusion proteins to reinvigorate immune responses against advanced stage cancers, particularly those with an immunologically cold ecosystem.