Background
NSCLC, cancer, TGF-β, lung cancer, T-cell infiltration, tumors, Cancer
METASTASIS, INFLAMMATORY RESPONSE, PROLIFERATION, CANCER, SOLID TUMORS, NON-SMALL CELL LUNG CANCER, TRANSFORMING, LUNG CANCER, NSCLC, TUMORS, TUMORIGENESIS, CANCER
Non-small cell lung cancer (NSCLC) accounts for approximately 85% of the incidences of lung cancer [Cancer immunotherapy aims to activate the host’s immune system to recognize and attack cancer cells. Recent successes in immunotherapy have been achieved by targeting immune checkpoints, i.e. a host of inhibitory receptors expressed on immune cells that upon activation suppress the inflammatory response [Programmed cell-death-1 (PD-1) is expressed on activated T-cells and can act to dampen the immune response [Transforming growth factor β (TGF-β) signaling plays an important role in tumorigenesis and contributes to many hallmarks of cancer cells including cell proliferation, invasion, escape of immune surveillance, angiogenesis, and metastasis [Galunisertib is an oral small molecule inhibitor of the TGF-β receptor 1 kinase that specifically down-regulates the phosphorylation of SMAD2 and is associated with an increase in T-cell infiltration in tumors [TGF-β can suppress or alter the activation, maturation, and differentiation of both innate and adaptive immune cells [In this study, both TGF-β and PD-1 were targeted using galunisertib in combination with nivolumab in patients with advanced refractory solid tumors and in patients with recurrent/refractory NSCLC who were PD-(L)1 naïve. The clinical trial objectives were to evaluate the safety and tolerability of the drug combination.