Cancer Immune Evasion and Immunotherapies: Progress and Challenges of CAR-T in Solid Tumors

Solid tumors account for nearly 90% of the global cancer diagnoses, which is over 20 million annually, making them a central focus in the global fight against cancer. Specifically, by downregulating antigen presentation and reprogramming innate immune cells, tumors can evade the immune system, creating a significant challenge for effective treatment. Furthermore, to overcome these challenges, multiple immunotherapies, including checkpoint inhibitors, vaccines, and adoptive immunotherapies, have been developed. While checkpoint inhibitors and vaccines have demonstrated progress, they depend on major histocompatibility complex-I (MHC-I)-mediated antigen recognition, causing cancer cells with mutated antigen presentation to remain undetected. On the other hand, chimeric antigen receptor T cell (CAR-T) therapy, a type of adoptive immunotherapy, involves engineering classical immune T cells in an ex vivo environment to bypass the MHC-antigen requirement. This MHC-independence allows CAR-T cells to recognize tumors more efficiently, overcoming the challenge posed by other recognized immune therapies. However, CAR-T therapies are primarily recognized for their success in treating B-cell leukemia, a type of white blood cell cancer, and their clinical application in solid tumors is limited. This review examines the current literature on cancer immune escape mechanisms and immunotherapies, with a focus on the obstacles that limit the effectiveness of CAR-T therapies in solid tumors. Additionally, it evaluates clinical trial findings, which indicate progress in survival and tumor control in the short term. Through these examinations, the review underscores the potential of CAR-T therapy for effective treatment of solid tumors.