Dendritic cell-activated cytokine-induced killer cell-mediated immunotherapy is safe and effective for cancer patients >65 years old

Abstract

Individuals >65 years old account for a large proportion of cancer patients, and usually have poor prognoses due to relative weaker physiological function and lower drug tolerance. To characterize the efficacy and safety of dendritic cell (DC)-activated cytokine-induced killer cell (CIK)-mediated treatment, and develop an adoptive immunotherapy for cancer patients >65 years old, a retrospective study was performed in 58 cancer sufferers who received 1-4 cycles of DC-activated CIK (DC-CIK) treatment and evaluated the response (tumor remission rate) and toxicity (side effects to the treatment). The present results showed that DCs and CIKs could be expanded rapidly in vitro, and following co-culture with DCs, the population of cluster of differentiation (CD) 3+, CD3+CD4+, CD3+CD8+ and CD3+CD56+ CIKs was significantly increased compared to CIKs without DC activation (P=0.044). In addition, DC-CIK infusion produced marked clinical outcomes, resulting in an objective remission rate, overall clinical benefit rate and Karnofsky performance status of 44.83, 75.86 and 87.28±5.46%, respectively, which was significantly improved compared with prior to treatment (P<0.05). Additionally, subsequent to two cycles of this immunotherapy, several tumor marker expression levels declined, returning to the normal range. The proportion of CD3+CD4+ (P=0.017) and CD3+CD8+ (P=0.023) lymphocytes, and the population of CD4/CD8 cells (P=0.024) were also increased. In conclusion, the present study suggests that the immunotherapy mediated by DC-CIK is safe and effective for cancer patients aged >65 years.

Keywords: cancer; cytokine-induced killer cells; dendritic cells; immunotherapy.

Figures

Figure 1.

Procedure for DC-CIK cells preparation and infusion. DC, dendritic cell; CIK, cytokine-induced killer cells; RBC, red blood cell; PBMC, peripheral blood mononuclear cell.

Figure 2.

Phenotype of CIK cells. The population of CD3+, CD3+CD4+, CD3+CD8+ and CD3+CD56+ CIKs were significantly increased by DCs activation compared with CIKs without DC activation. *P<0.05. CD, cluster of differentiation; CIK, cytokine-induced killer cell; DC, dendritic cell.

Figure 3.

Tumor marker level of patients. The levels of tumor markers were monitored prior to and subsequent to 2 cycles of DC-CIK immunotherapy using FCM. (A) The expression of CEA in 15 cases. Expression in 13 patients decreased significantly compared with prior to DC-CIK infusion, and the expression in 7 patients reached the normal range. (B) The expression of CA199 in 8 patients. Expression in 7 patients decreased significantly compared with prior to DC-CIK infusion, and the expression in 1 patient reached the normal range. (C) The expression of NSE in 4 cases. The expression of all 4 patients decreased compared with prior to DC-CIK infusion, and 2 patients demonstrated a decrease to the normal range. (D) The expression of AFP in 2 cases. AFP expression in the 2 patients decreased compared with prior to DC-CIK infusion. (E) The expression of CA-724 in 2 cases. The expression of CA-724 decreased significantly in the 2 patients compared with prior to DC-CIK infusion, and the level in 1 patient reached the normal range. *P

Figure 4.

Lymphocyte subpopulation of patients. The lymphocyte subpopulation was detected prior to and subsequent to 2 cycles of DC-CIK immunotherapy in 8 patients. (A) The proportion of CD3+ lymphocytes. In total, 6 patients showed CD3+ lymphocyte increase following DC-CK treatment. (B) The proportion of CD3+CD4+ lymphocytes was analyzed in 8 cases, and 6 patients showed CD3+CD4+ lymphocyte increase following DC-CK treatment. (C) The proportion of CD3+CD8+ lymphocytes. In total, 4 patients showed CD3+CD8+ lymphocyte increase following DC-CIK treatment. (D) The ratio of CD4 and CD8 lymphocytes. Overall, 6 patients showed increased levels. *P<0.05. DC, dendritic cell; CIK, cytokine-induced killer cell; CD, cluster of differentiation.