Immune checkpoint inhibitors (ICIs) have recently emerged as strong therapies for a broad spectrum of cancers being the first-line treatment for many of them, even improving the prognosis of malignancies that were considered untreatable. This therapy is based on the administration of monoclonal antibodies targeting inhibitory T-cell receptors, which boost the immune system and prevent immune evasion. However, non-specific T-cell de-repression can result in a wide variety of immune-related adverse events (irAEs), including gastrointestinal, endocrine, and dermatologic, with a smaller proportion of these having the potential for fatal outcomes such as neurotoxicity, pulmonary toxicity, and cardiotoxicity. In recent years, alarm has been raised about cardiotoxicity as it has the highest mortality rate when myocarditis develops. However, due to the difficulty in diagnosing this cardiac condition and the lack of clinical guidelines for the management of cardiovascular disease in patients on therapy with ICIs, early detection of myocarditis has become a challenge in these patients. In this review we outline the mechanisms of tolerance by which this fatal cardiomyopathy may develop in selected cancer patients treated with ICIs, summarize preclinical models of the disease that will allow the development of more accurate strategies for its detection and treatment, and discuss the challenges in the future to decrease the risks of its development with better decision making in susceptible patients.

The central nervous system (CNS) has long been considered an immune‐privileged site, with minimal interaction between immune cells, particularly of the adaptive immune system. Previously, the presence of immune cells in this organ was primarily linked to events involving disruption of the blood‐brain barrier (BBB) or inflammation. However, current research has shown that immune cells are found patrolling CNS under homeostatic conditions. Specifically, T cells of the adaptive immune system are able to cross the BBB and are associated with aging and cognitive impairment. In addition, T‐cell infiltration has been observed in pathological conditions, where inflammation correlates with poor prognosis. Despite ongoing research, the role of this population in the aging brain under both physiological and pathological conditions is not yet fully understood. In this review, we provide an overview of the interactions between T cells and other immune and CNS parenchymal cells, and examine the molecular mechanisms by which these interactions may contribute to normal brain function and the scenarios in which disruption of these connections lead to cognitive impairment. A comprehensive understanding of the role of T cells in the aging brain and the underlying molecular pathways under normal conditions could pave the way for new research to better understand brain disorders.