Capillary-Leak Syndrome: An Unrecognized Early Immune Adverse Effect Of Checkpoint-Inhibitors Treatment

Lay abstractModern cancer treatment increasingly relies on means that encourage the patient's immune system to attack and destroy existing cancer cells. These means are very effective compared with standard treatments. However, the activation of the immune system is sometimes associated with untoward effects as a result of an attack of bystanding healthy tissues by the overactivated immune system and excessive inflammatory processes that accompany the immune response. We describe here two patients treated with immune checkpoint inhibiting drugs that developed transient extensive edema attributed to leakage of serum proteins and water from small blood vessels into the surrounding tissues (so-called 'capillary-leak syndrome'), after the drug-induced activation of the immune system. In both patients, the edema subsided following specific interventions.Capillary-leak syndrome is strongly associated with cytokine activity states. It is an ill-recognized adverse effect of checkpoint inhibitors treatment, which are typically associated with cellular immune response. We describe two patients with capillary leak syndrome following immune checkpoint inhibitors treatment. We present linking mechanisms between checkpoint inhibitors, cellular immunity, cytokine action and endothelial damage. We suggest that capillary-leak syndrome is a unique adverse effect of immunotherapy, resulting from complex interactions between cellular and cytokine activation and that its expression is probably depending on inherent host immune variabilities.