Exploring the Therapeutic Potential of ICOS and GITR Agonists in Lung Cancer

Lung cancer, being the second most prevalent cancer occurring in both males and females in the United States, is one of the most frequently reported types of cancer worldwide. Some immunological checkpoint proteins that aid in the dysfunction of antitumour immunity and boost the proliferation and division of cancer cells have been identified to be expressed by some malignant cells. Cancer immunotherapy is a widely explored therapeutic arena that focuses to strengthen the body’s immune system to attack cancerous cells by targeting the immune regulatory pathways. ICOS (inducible T-cell co-stimulator) and GITR (glucocorticoid-induced tumour necrosis factor receptor)-related protein are two of the co-stimulatory molecules that amplify the immune response against the tumour cells. ICOS is found to be encoded on the membranes of the activated T-cells and aids in the activation and differentiation of T-cells. The ICOS/ICOSL (inducible T-cell co-stimulator ligand) pathway serves a dual function of pro-tumour as well as the antitumour function, whereas GITR is localised on various immune cells and is associated with the modulation of immune responses. Like ICOS, GITR too exhibits both activating and inhibitory effects on immune cells. Many research studies have explored both GTIR and ICOS as potential targets for immunotherapy in lung cancer. Various in vitro studies have also testified the efficacy of ICOS/GTIR agonists in downregulating the progression of lung cancer cells along with significant improvement in the overall survival of patients suffering from advanced non-small cell lung cancer (NSCLC). This chapter explores the utility of ICOS and GITR agonists as potential arsenal in the treatment of lung cancer.