Next-generation cancer treatment: exploring the tumor microenvironment and CAR-T cell therapy potential

Cancer is still one of the most common causes of death worldwide; the tumor microenvironment plays a key role in cancer development and treatment resistance. It has been reported that CAR-T cell immunotherapy is one of the most promising approaches. However, when considering solid tumors, difficulties are posed by TME complexity and its immunosuppressive nature. The paper review discusses the interaction of TME with CAR-T cell treatment, including the mechanisms of how the outcome is affected by the treatment and how the therapeutic efficiency of CAR-T cells could be improved. TME significantly influences the immune responses; the tumor-associated macrophages and regulatory T cells within TME are identified as major contributing cells toward an immunosuppressive environment; CAR-T cell therapy is relatively effective in hematological malignancies but not in solid tumors due to dense TME; and promising strategies involve TME modulation, cytokine engineering, and combination therapies. Improving the outcomes of CAR-T cell therapy crucially depends on the dynamics of the TME, as the elucidation of immune evasion, metabolic competition, and immunosuppressive factors has necessitated novel approaches. Personalization of CAR-T therapy according to unique characteristics of the TME and new strategies have led to better outcomes for patients. Further research is needed for translation into the clinical setting since findings are continuously being unraveled, thereby expanding the use of CAR-T therapy into a wide array of cancer types.