Use of cytokine-induced killer cell therapy in colorectal cancer patients: a systematic review and meta-analysis
Authors: Ying Li Celine Man , Tomita Yoko , Dhakal Bimala , Li Runhao , Li Jun , Drew Paul , Price Timothy , Smith Eric , Maddern Guy J. , Fenix Kevin 
Published: January 2023

AbstractBackgroundThe number of clinical studies evaluating the benefit of cytokine-induced killer cell (CIK) therapy, an adoptive immunotherapy, for colorectal cancer (CRC) are increasing. In many of these trials CIK therapy was co-administered with conventional cancer therapy. The aim of this review is to systematically assess the available literature, in which the majority were only in Chinese, on CIK therapy for the management of CRC using meta-analysis, and to identify parameters associated with successful CIK therapy implementation.MethodsProspective and retrospective clinical studies which compared CIK therapy to non-CIK therapy in CRC patients were searched for electronically on MEDLINE, Embase, CNKI and Wanfang Data databases. The clinical endpoints of overall survival (OS), progression-free survival (PFS), OS and PFS rates, overall response rate (ORR) and toxicity were meta-analysed using hazard (HR) and relative ratios (RR), and subgroup analyses were performed using Chi-square (Chi2) test and I-square (I2) statistics for study design, disease stage, co-therapy type, and timing of administration.ResultsIn total, 70 studies involving 6,743 patients were analysed. CIK therapy was favoured over non-CIK therapy for OS (HR=0.59, 95% CI: 0.53-0.65), PFS (HR=0.55, 95% CI: 0.47-0.63), and ORR (RR=0.65, 95% CI: 0.57-0.74) without increasing toxicity (HR=0.59, 95% CI 0.16-2.25). Subgroup analyses on OS and PFS by study design (randomised versus non-randomised study design), disease stage (Stage I-III versus Stage IV), co-treatment with dendritic cells (CIK versus DC-CIK therapy), or timing of therapy administration (concurrent versus sequential with co-administered anti-cancer therapy) also showed that the clinical benefit of CIK therapy was robust in any subgroup analysis. Furthermore, co-treatment with dendritic cells did not improve clinical outcomes over CIK therapy alone.ConclusionsCompared with standard therapy, patients who received additional CIK cell therapy had favourable outcomes without increased toxicity, warranting further investigation into CIK therapy for the treatment of CRC.Key MessageWhat is already known on this topicCytokine-induced killer cell (CIK) therapy is an adoptive immunotherapy used to treat both solid and haematological cancers for over 20 years. It is predominantly used in China, with multiple studies reporting benefit in colorectal cancer (CRC) patients. Despite this, CIK therapy treatment regimens are not widely used, possibly due in part to the majority of the literature about CIK therapy in CRC being reported in Chinese. Further, CIK therapy is commonly combined with other therapies but it is currently not known if there is a specific combination or treatment regimen that is optimal for CRC.What this study addsWe report the most comprehensive systematic review to date of CIK therapy for CRC patients, combining both Chinese and English language reports. Patients with CRC who received additional CIK therapy had better survival outcomes than with standard therapy alone. We also showed that the addition of dendritic cells (DC) to CIK therapy, common for CRC treatment, did not provide any clinical benefit over CIK therapy alone, and that CIK therapy is effective whether given concurrently or sequentially to standard treatment regimens.How this study might affect research, practice, or policyOur systematic review of Chinese and English publications shows that CRC patients benefit from the addition of CIK therapy to standard treatment protocols and warrants further international studies.