Harman  Saman,Shahab  Uddin,Syed  Raza,Raj  Shrimali,Kakil  Rasul,
Understanding Checkpoint Inhibitors in Cancer Therapy, Mechanisms of Action, Resistance and Future Challenges
Clinical Oncology and Research
2020
2613-4942
http://dx.doi.org/10.31487/j.COR.2020.09.08
https://www.sciencerepository.org/understanding-checkpoint-inhibitors-in-cancer-therapy-mechanisms-of-action_COR-2020-9-108 
Abstract: The immune system is the human body’s natural defence against mutated cells produced as the result of
DNA replicative error or by the effect of carcinogens, a process rereferred to as immune surveillance.
‘Escaping’ of cancer cells from immune surveillance leads to tumor development, metastasis and
progression. Avoiding detection and destruction by the immune system are the result of cancer cells
evolution, caused primarily by cancer cells’ genomic instability. On the other hand, scientists attempted for
decades to exploit the anticancer effect of the immune system with limited success. However, better
understanding of the mechanisms behind the cancer cells’ ability to avoid detection and suppression by the
immune system resulted in the development of immune checkpoint inhibitors, a form of immunotherapy,
first approved by the Food and Drug Administration (FDA) in 2011. This article reviews the pathways
involved in anticancer immune response, evading and supressing of the immune system by cancer cells
mechanisms of action and successes of immune checkpoint inhibitors (ICI), particularly programmed death1 (PD-1) and programmed death-ligand (PD-L1) inhibitors as well as mechanisms that result in resistance
of cancer cells to ICI.Keywords:   Immune check point inhibitors, resistance to immune check point, inhibitors, mechanism of action of immune check point inhibitors, tumor microenvironment, cancer immunotherapy, cancer immunology