Cancer immunotherapy with immune checkpoint inhibitors and infections: A particular focus on mycobacterial infections

Abstract

Cancer treatment is undergoing a major transformation with the advent of immunotherapy with immune checkpoint inhibitors. These drugs, which have a different mechanism of action from conventional cytotoxic chemotherapy, are transforming treatment paradigms for many patients suffering from advanced cancer. On the other hand, they are often complicated by specific adverse events, known as immune-related adverse events (irAEs). Infections occurring during immunotherapy with immune checkpoint inhibitors have recently received increasing attention and sometimes are seen as part of irAEs. Amongst these, mycobacterial infections have attracted particular attention. Recent reports have shown that infections occurring during immunotherapy can not only be caused by immunosuppression, but in addition new type of infections are observed that are not caused by immunosuppression. Specifically, tuberculosis (TB) has recently been shown to develop as a result of an imbalance in immunoregulation and an excessive immune response. This review highlights reports of infections during immunotherapy with immune checkpoint inhibitors, followed by a focus on the association with TB and nontuberculous mycobacteria. It concludes with a discussion of the possible mechanisms of pathogenesis and the implications for clinical practice.

Keywords: Immune checkpoint inhibitor; Immunotherapy; Infection; Nontuberculous mycobacteria; Tuberculosis.