Mazdak Ganjalıkhani-Hakemi, Gulderen Yanikkaya Demirel, Xin He, Chengwu Zeng
Cancer immunotherapy harnesses the body’s immune system to combat tumors while sparing normal cells. Numerous strategies have been explored for this purpose. However, monotherapy using these methods often proves ineffective in clinical trials. Many tumors resist immunotherapy, earning them the designation of “cold” or non-inflammatory tumors. These cold tumors lack sufficient infiltration by CD8+ T cells, hampering immune response. They are characterized by a dearth of cytotoxic T cells, alongside the presence of anti-inflammatory myeloid cells, tumor-associated M2 macrophages, and regulatory T cells. Combining immunotherapy with other cancer treatment modalities, such as chemotherapy or cancer vaccines, holds promise in bolstering efficacy and improving outcomes (1–3).
In their article titled “Overcoming cold tumors: a combination strategy of immune checkpoint inhibitors,” Ouyang et al. have explored methods to convert cold tumors into hot ones, including boosting T cell infiltration and adopting therapies like CAR T cells. Despite the groundbreaking impact of Immune Checkpoint Inhibitors (ICIs) on cancer therapy, resistance persists in many cold tumors due to diverse immune evasion mechanisms. The success of immunotherapy hinges on T cells’ capacity to recognize and eliminate tumor cells; however, cold tumors lack T cell infiltration, rendering ICI therapy ineffective. Overcoming these challenges, particularly impaired T cell activation and homing, is essential for enhancing ICI therapy efficacy.