The article discusses the challenges of treating "cold" tumors, which are characterized by low immune cell infiltration and resistance to immune checkpoint inhibitors (ICIs). Cold tumors are distinguished from "hot" tumors, which have high immune cell infiltration and respond well to ICIs. The article explores the mechanisms by which cold tumors evade immune detection, including the lack of tumor antigens, defective antigen presentation, and the inability of T cells to infiltrate the tumor bed. It also highlights the role of immune checkpoint pathways, such as PD-1 and PD-L1, in suppressing T cell activity and enabling tumor immune evasion. The article emphasizes the need for combination therapies to overcome the resistance of cold tumors, including dual ICIs, CAR-T cell therapy, cancer vaccines, oncolytic viruses, and macrophage-targeted therapies. It also discusses the potential of combining ICIs with other immunotherapies, such as T cell redirecting bispecific antibodies, to enhance immune responses against tumors. The article concludes with a review of various therapeutic strategies, including radiotherapy and chemotherapy, which can be combined with ICIs to improve treatment outcomes for patients with cold tumors. The study underscores the importance of understanding the tumor microenvironment and immune evasion mechanisms to develop more effective treatment strategies for cold tumors.The article discusses the challenges of treating "cold" tumors, which are characterized by low immune cell infiltration and resistance to immune checkpoint inhibitors (ICIs). Cold tumors are distinguished from "hot" tumors, which have high immune cell infiltration and respond well to ICIs. The article explores the mechanisms by which cold tumors evade immune detection, including the lack of tumor antigens, defective antigen presentation, and the inability of T cells to infiltrate the tumor bed. It also highlights the role of immune checkpoint pathways, such as PD-1 and PD-L1, in suppressing T cell activity and enabling tumor immune evasion. The article emphasizes the need for combination therapies to overcome the resistance of cold tumors, including dual ICIs, CAR-T cell therapy, cancer vaccines, oncolytic viruses, and macrophage-targeted therapies. It also discusses the potential of combining ICIs with other immunotherapies, such as T cell redirecting bispecific antibodies, to enhance immune responses against tumors. The article concludes with a review of various therapeutic strategies, including radiotherapy and chemotherapy, which can be combined with ICIs to improve treatment outcomes for patients with cold tumors. The study underscores the importance of understanding the tumor microenvironment and immune evasion mechanisms to develop more effective treatment strategies for cold tumors.