Susceptible loci associated with autoimmune disease as potential biomarkers for checkpoint inhibitor-induced immune-related adverse events

Hoefsmit, E.P.; Rozeman, E.A.; Haanen, J.B.A.G.; Blank, C.U.

doi:doi:10.1136/esmoopen-2018-000472

Unprecedented successes regarding cancer immunotherapy have been achieved, in which therapeutic agents are used to target immune cells rather than cancer cells. The most effective immunotherapy to date is the group of immune checkpoint inhibitors (CPI), targeting, for example, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) or programmed cell death protein (PD-1). TThe combination of these therapies (anti-PD-1 with anti-CTLA-4) induces high response rates, and seem to be increased further when applied in early-stage disease. However, combined CTLA-4 plus PD-1 blockade causes frequent high-grade immune-related adverse events (irAE). To date, research on biological mechanism of irAEs is scarce and no widely accepted biomarkers predicting onset of severe irAEs have been identified. The similarity of irAEs to autoimmune disorders fuels the hypothesis that irAEs may be linked to susceptible genetic loci related to various autoimmune diseases. In this review, we extensively searched...Show moreUnprecedented successes regarding cancer immunotherapy have been achieved, in which therapeutic agents are used to target immune cells rather than cancer cells. The most effective immunotherapy to date is the group of immune checkpoint inhibitors (CPI), targeting, for example, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) or programmed cell death protein (PD-1). TThe combination of these therapies (anti-PD-1 with anti-CTLA-4) induces high response rates, and seem to be increased further when applied in early-stage disease. However, combined CTLA-4 plus PD-1 blockade causes frequent high-grade immune-related adverse events (irAE). To date, research on biological mechanism of irAEs is scarce and no widely accepted biomarkers predicting onset of severe irAEs have been identified. The similarity of irAEs to autoimmune disorders fuels the hypothesis that irAEs may be linked to susceptible genetic loci related to various autoimmune diseases. In this review, we extensively searched for susceptible loci associated with various autoimmune diseases, and pooled them in groups most likely to be associated with CPI-induced irAEs. These sets could be used in future research on predicting irAEs and guide physicians in a more refined and personal manner.Show less

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Susceptible loci associated with autoimmune disease as potential biomarkers for checkpoint inhibitor-induced immune-related adverse events