The promising results of immune checkpoint inhibitors (ICIs) in tumors have changed the current treatment modality for cancer. ICIs response prediction is urgently needed for the personalized therapy approach. In the recent issue of the Journal of Oncology, Zixin Hu et al. proposed that DNA methylation alternations contribute to tumor microenvironment (TME) reshapement to predict the ICIs response. Notwithstanding the global DNA methylation loss, the repression of T cell receptor signaling and the fellow costimulators by DNA hypermethylation contributed to the cold TME and ICIs resistance.

Immune checkpoint inhibitors (ICI) have emerged as promising treatment options for many cancers. ICIs exert their therapeutic effects by targeting immune inhibitory molecules on T-cells in adaptive immunity, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death 1 (PD-1) and its ligand programmed cell death ligand 1 (PD-L1). ICIs, however, can result in a wide variety of immune-related adverse events (iRAE), including myocarditis, a rare and potentially deadly complication that necessitates early diagnosis.

The advent of immune checkpoint inhibitors (ICI) targeting CTLA-4 and PD-1/PD-L1 pathways has revolutionized cancer treatment with significantly improved outcomes across a spectrum of cancers [1,2]. Although ICI therapy offers significant clinical benefits, these treatments can also lead to various immune-related adverse events (irAEs) that may negatively impact patient outcomes. Although the precise mechanism of irAE is not fully understood, they demonstrate many clinical features similar to autoimmune diseases. IRAEs are thought to result from bystander effects of activated T-cells, cross-reactivity between tumor and host tissues, and the role of the gut microbiome in immune activation [3].