Clinical application of cytokine-induced killer cells in cancer immunotherapy

Cytokine-induced killer (CIK) cells exhibit potent antitumor activity with reduced dependence on strict MHC compatibility, mediated by a combination of T-cell receptor (TCR)-dependent recognition and natural killer (NK)-like, MHC-unrestricted cytotoxicity. This narrative review synthesizes evidence from clinical trial evaluations, including 48 published studies. We examine strategies to enhance CIK function, such as engineering, combination with checkpoint inhibitors, and co-administration with dendritic cells. CIK cell therapy effectively reduces post-treatment recurrence in the adjuvant setting and enhances chemotherapy outcomes in advanced disease, significantly improving key survival metrics across multiple cancers. A detailed analysis is conducted of ongoing challenges, such as immunosuppressive conditions in tumor microenvironments, limited in vivo durability, product variability, and choosing the best treatment plans. Future advancements in translation depend on establishing standardized manufacturing procedures, developing treatment algorithms guided by precision biomarkers, and validating next-generation engineered CIK cell products in clinical settings.