Retrospective analysis of the efficacy of cytokine‐induced killer cell immunotherapy combined with first‐line chemotherapy in patients with metastatic colorectal cancer

Abstract

Objectives Fluoropyrimidine‐based chemotherapy regimens are the current first‐line treatment for metastatic colorectal cancer (mCRC); however, the outcome is often unsatisfactory. The present study aimed to determine the effect of combined cytokine‐induced killer (CIK) cell immunotherapy and first‐line chemotherapy in patients with mCRC. Methods This retrospective study included 252 patients with mCRC treated with first‐line chemotherapy. Among them, 126 patients received first‐line chemotherapy only (control group), while the other 126 patients, with similar demographic and clinical characteristics, received CIK cell immunotherapy combined with first‐line chemotherapy (CIK group). Overall survival (OS) and progression‐free survival (PFS) were compared between the two groups using the Kaplan–Meier method. Results The median OS for the CIK group was 54.7 versus 24.1 months for the controls, and the median PFS for the CIK group was 25.7 versus 14.6 months for the controls. Univariate and multivariate analyses indicated that CIK cell treatment was an independent prognostic factor for patients' OS and PFS. Subgroup analyses showed that CIK cell treatment significantly improved the OS and PFS of patients with metastatic colon cancer, but not those with metastatic rectal cancer. Additionally, the change in CD3+CD56+ subsets after the fourth treatment cycle might be an indicator of successful CIK cell treatment: Patients with increased CD3+CD56+ subsets had better survival than those with decreased CD3+CD56+ subsets. Conclusion Cytokine‐induced killer cell immunotherapy combined with first‐line chemotherapy could significantly improve the OS and PFS of patients with mCRC, particularly for patients with metastatic colon cancer.

Retrospective analysis of the efficacy of adjuvant cytokine‐induced killer cell immunotherapy combined with chemotherapy in colorectal cancer patients after surgery

“…These findings, showing that postoperative CIT treatment could significantly prolong OS and PFS and reduce the rate of metastasis and recurrence in CRC patients, were consistent with results in patients with ovarian cancer, non-small lung cancer, triplenegative breast cancer, gastric cancer and liver cancer, as well as in patients with CRC metastases. [20][21][22][23][24][25][26] Subgroup analyses showed that, compared with chemotherapy alone, CIT improved the OS and PFS in CRC patients with stage II, but not stage III/ IV. Moreover, CIT treatment was more effective than chemotherapy alone in CRC patients at advanced T (T3/T4) and earlier N (N0) stage.…”

“…3 In addition, this combination was associated with few side effects, such as fever, fatigue and myalgia. 26 Although several clinical studies have assessed the efficacy of CIK cell treatments, less is known about the clinical indications for these treatments or factors, especially the molecular biomarkers, predictive of their long-term efficacy.…”

Cytokine-induced killer cells mediated pathways in the treatment of colorectal cancer

“…evaluated the relationship between the percentage of CD3+CD56+ subset in CIK cells and survival of treated metastatic CRC patients and showed that no significant differences were observed in the OS and progression-free survival (PFS) in higher ratios of CD3+CD56+ subset in the first cycle. However, after the fourth cycle, the increase in the CD3+CD56+ subset was associated with improved OS and PFS [ 25 ].…”

“…In subgroup analysis, in patients with metastatic colon cancer and patients with one metastatic site, CIK therapy significantly prolonged PFS and OS. In both studies mentioned above, no severe side effects were observed among CIK therapy patients [ 23 , 25 ].…”

“…1, 3, 5-year OS were also higher in the study group ( P = 0.001) 6 patients receiving DC-CIK developed mild fever, chills, and fatigue; and three and one patients experienced headache and chest tightness with hypotension, respectively Liu [ 15 ] 2019 II, III, IV Cohort study NA 35 35 4 courses of 5*10 9 DC-CIK cells from day 14 to 16 + 4 to 6 cycles of chemotherapy with XELOX from day 1 to 14 (duration of a cycle: 21 days) 4 to 6 cycles of chemotherapy with XELOX from day 1 to 14 (duration of a cycle: 21 days) The ORRs in the study and control groups are 60% and 31%, respectively. The effectiveness ( ) was significantly higher in the study group ( P < 0.05) The side effects were significantly lower in the study group Pan [ 23 ] 2020 II, III, IV Retrospective study 54.5 60 62 Complete resection + 4 cycles of CIK cell immunotherapy 4 weeks after chemotherapy with 1-week interval and the 4 cycles with 2-weeks interval + adjuvant chemotherapy (FOLFOX or XELOX or single-agent Capecitanine regimen) Complete resection + adjuvant chemotherapy (FOLFOX or XELOX or single-agent Capecitanine regimen) The DFS and OS rate significantly improved in the CIK group as compared to the control group ( P = 0.0024 and P = 0.008, respectively) Among CIK receiving patients, only 10 patients developed side effects (fever, transient hypertension, pruritus, fatigue) Pan [ 25 ] 2020 IV Retrospective study 55.2 126 126 12*10 10 CIK cell infusions every 2 or 3 weeks in intervals of chemotherapy + Chemotherapy with FOLFOX, FOLFIRI, or XELOX regimen, with or without bevacizumab or cetuximab Chemotherapy with FOLFOX, FOLFIRI, or XELOX regimen, with or without bevacizumab or cetuximab The median OS was significantly higher in the CIK group as compared to the control group (54.7 vs 24.1 months; P < 0.0001). The median PFS was also significantly improved in the CIK group (25.7 vs. 14.6 mont...…”