Often the body's natural defense system can distinguish the cancer cells from healthy cells but sometimes the immune response is insufficient to clear the cells. In other cases, cancer cells find a way to escape this immune response. This is also the case with the JAK2 and CALr mutations that we know in MPN diseases. With immunotherapy we strengthen and manipulate the immune system to still switch off the cancer cells. The mutated cancer cells can put a brake on the T cells. T cells are a certain type of immune cells. Because of this brake, the T cells cannot clear the cancer cells and they continue to multiply.
A new immunotherapy takes the brakes off the T cells, so the own immune system can attack and clean up the abnormal cells. These drugs are checkpoint inhibitors. Roughly speaking, 2 groups of checkpoint inhibitors can be distinguished: Group 1 that inhibits the checkpoint PD-1 and Group 2 that inhibits CTLA-4.
Prestipino et al. found that myeloproliferative cancers with overactive JAK2 also have elevated PD-L1. PD-L1 helps cancer cells escape the immune system. The immune checkpoint inhibitors (developed in recent years) can block its function and convert PD-L1 expression into a therapeutic vulnerability to the tumors.
And this is very good news for the MPN people! Current treatments have left a lot to be desired for years and focus only on symptom control. The sensitivity of the JAK2v617f mutation to PD-1 targeting paves the way for immunomodulatory approaches based on PD-1 inhibition. The big advantage is that treatment with immune checkpoint inhibitors is already available in most university hospitals! Attached are a number of studies, including a first report demonstrating the effectiveness of PD-L1 treatment in an ET patient:
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