Effectiveness of immune therapy combined with chemotherapy on the immune function and recurrence rate of cervical cancer

Survival rate

Survival rate

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Summary

The study aims to compare the immune function of the treatment with biological immune therapy combined with chemotherapy on patients with cervical cancer. As a result, treatment with DC-CIK cells combined with chemotherapy improved the immune function, reduced recurrence rate and prolonged the survival time of patients with cervical cancer.

Patients characteristics

79 patients diagnosed with cervical cancer by pathology ages between 30 and 70 years old, without organ lesions, e.g., of the liver, kidney or heart, without cardiovascular and psychiatric disorders.

Methodology

The patients were randomly divided into a control group and an experimental group. The patients of the control group were treated with chemotherapy, while the patients of the experimental group were treated with biological immune therapy combined with chemotherapy.
The control group consisted of 39 cases (age, 51.9±16.8 years), 30 of whom had squamous cell carcinoma and nine of whom had adenocarcinoma. According to International Federation of Gynecology and Obstetrics (FIGO) stage classification, there were 16 cases in Stage IIa, 11 cases in Stage IIb, seven cases in Stage IIIa, four cases in Stage IIIb, and one case in Stage IV.
The experimental group consisted of 40 cases (age, 52.4±17.1 years), 31 of whom had squamous cell carcinoma and nine of whom had adenocarcinoma. According to FIGO stage classification, there were 15 cases in Stage IIa, 12 cases in Stage IIb, eight cases in Stage IIIa, four cases in Stage IIIb and one case in Stage IV.
Preparation of DC-CIK cell
PBMCs were collected from each patient and were centrifuged at 2,500 x g for 10 min, and the supernatant was decanted. The sediment was washed with phosphate-buffered saline (PBS) twice and then resuspended. After that, the PBMCs were mixed with lymphocyte separation medium in a 1:1 ratio, centrifuged at 3,000 x g for 15 min and the supernatant was decanted. The PBMCs were washed with normal saline three times, and then resuspended in serum-free medium to modulate the cells. The suspension was divided into two parts in the ratio of 1:9. The cell density of the small part of the suspension was adjusted to 1-2×107/ml. Then, the suspension was seeded in 6-well plates (2 ml/plate), adherently cultured for 2 hours in an incubator and then the non- adherent cells were sucked out. Serum-free medium containing granulocyte- macrophage colony-stimulating factor (GMCSF) and interleukin (IL)-4 was added for culturing DCs and replaced every 3 days.
On day 7, tumor necrosis factor (TNF)-α was added to promote maturation. The large part of the suspension was mixed with interferon (INF)-γ and used as CIK serum-free medium, in which IL-1α, IL-2 and CD3 monoclonal mouse anti-human antibodies were added from day 2 and replaced every 3 days.
On day 8, the mature DCs were collected and divided into two portions. One portion of the DCs was washed with normal saline 3 times and then resuspended in 2 ml autologous plasma. The other portion of the DCs was mixed and co-cultured with CIK cells at a ratio of 1:10 for 7 days to construct the DC-CIK cell mixture.

Treatment

Patients in the control group were given conventional chemotherapy with cisplatin. This involved dissolving 20 mg cisplatin in 250 ml normal saline, and then administered by intravenous drip within 2 hours with the avoidance of light. One course of treatment lasted for 10 days.
The experimental patients were given the same chemotherapy as that given to the patients in the control group. However, the experimental patients were also given a reinfusion of DC-CIK cells after the chemotherapy. Three months later, all patients from these two groups were given a second course of treatment. DC-CIK cells were reinfused to patients once a day for a total of four times and the total number of cells was 2-3.5×10.

Results

The lymphocyte ratio in the experimental group was significantly higher than that in the control group. The positive expression levels of perforin, GraB and CD107a of PBMCs in the experimental group following treatment were significantly higher than those prior to treatment and those of the control group.
Eighteen recurrent cases were found in the control group but only nine recurrent cases were found in the experimental group.
Kaplan-Meier curves demonstrated that the cumulative 1-year, 2-year and 3-year recurrence rates in the control group were 28.2% (11 cases), 35.9% (14 cases) and 46.2% (18 cases), respectively. In the experimental group, the cumulative recurrence rates were 5% (2 cases), 15% (6 cases) and 22.5% (9 cases), respectively.
The cumulative 1-year, 2-year and 3-year survival rates in the control group were 92.31, 76.92 and 56.41%, respectively. In the experimental group, the cumulative survival rates were 97.25, 90 and 80%, respectively. Log-rank test showed that the cumulative survival rate of the experimental group was significantly different from that of the control group.

Conclusion

In conclusion, in postoperative patients with cervical cancer, treatment with DC-CIK cells combined with cisplatin chemotherapy significantly improved the immune function, reduced the recurrence rate and prolonged the survival time of the patients.

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Scientific article publishing date 1/7/2015

Immucura identifier BSC21_253EN

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