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Immune Checkpoint Inhibitors

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The Mechanism of Immune Checkpoint Inhibitors

Though there are multiple treatment domains within “cancer immunotherapy,” a major source of excitement has been the discovery and the proven efficacy of immune checkpoint inhibitors – Ipilimumab, Nivolumab, Pembrolizumab. These drugs operate on the basis that our own immune cells can recognize and eliminate self-cells (and malignant cells), but are usually inhibited from doing so by specific receptors and ligand complexes. These mechanisms normally serve to maintain self-tolerance and limit collateral tissue damage during immune responses, but are exploited by cancers to evade immune effector cells.[2]

Essentially, immune checkpoints occur during the 1) priming/activation and 2) effector phases
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IRAEs tend to follow a predictable pattern, with rashes and GI toxicity seen early and liver toxicity or endocrinopathies seen later in the treatment course. [13] Certain IRAEs appear to be specific to certain cancers, with pneumonitis being more prevalent in lung cancer patients and higher rates of vitiligo and colitis observed in melanoma patients receiving infusions immune check point inhibitors.[14] In general, anti-PD-1 antibodies, Nivolumab/Pembrolizumab, are more tolerable (10-15% rate of grade 3 [severe] and 4 [life-threatening] AEs) compared to Ipilimumab (20–30% rate of grade 3-4 AEs) and or combination PD-1 + CTLA-4 blockade therapy (55% rate of AEs).[14] Immune modulators (IMMs) are employed for high grade IRAEs and most patients achieve control with steroids or infliximab for steroid-refractory toxicity.[3] Fortunately, it has been shown that treating IRAEs with steroids/IMMs has yet to show any detrimental effect on the efficacy of immune check point therapy in terms of OS and
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