The editorial focuses on regulators of the immune tumor microenvironment as a new frontier in cancer immunotherapy. The tumor microenvironment (TME) is a complex ecosystem composed of tumor, stromal, and immune cells that influence cancer progression and response to treatment. Many patients with solid tumors do not respond to immunotherapy due to immunosuppressive TME. The aim is to investigate the regulation of the immune TME in solid tumors and to identify epigenetic pathways that can be targeted therapeutically. It includes studies characterizing the composition and heterogeneity of the immune TME, identifying key regulators such as T-cells, regulatory T-cells, MDSCs and CAFs. It also focuses on the mechanisms by which epigenetic mechanisms control these regulators and the development of new epigenetic therapies to improve the efficacy of immunotherapy. Targeting the immune TME can overcome resistance to immunotherapy and improve outcomes for cancer patients.[2][5]