Immune checkpoint inhibitors (ICIs), while transformative for cancer therapy, are linked to serious immune-mediated side effects including myocarditis and pericarditis, raising safety concerns. New research elucidates complex immune and inflammatory interactions, such as the role of astrocyte-derived CXCL10 in exacerbating brain injury post-hemorrhage. Additionally, studies reveal tumor microenvironment mechanisms whereby nociceptors promote immunosuppression, undermining anti-tumor immunity. These findings underscore the delicate balance between therapeutic benefit and adverse immune response, informing safer immunotherapeutic strategies.