Increasing the frequency of CIK cells adoptive immunotherapy may decrease risk of death in gastric cancer patients

doi:10.3748/wjg.v16.i48.6155

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Dec 28, 2010; 16(48): 6155-6162
Published online Dec 28, 2010. doi: 10.3748/wjg.v16.i48.6155

Table 1 Distribution of demographic and clinical characteristics in two groups

Demographic and clinical features	n	Groups, n (%)		χ²	P
Demographic and clinical features	n	Group I	Group II
Sex
Men	122	62 (76.5)	60 (80)	0.273	0.601
Women	34	19 (23.5)	15 (20)	0.273	0.601
Age (yr)
≤ 45	14	7 (8.6)	7 (9.3)	0.047^a	0.977
45 < age ≤ 60	71	36 (44.5)	35 (46.7)
> 60	71	38 (46.9)	33 (44.0)
Tumor site^b
Gastric cardia
Yes	58	30 (37.0)	28 (37.3)	0.002	0.970
No	98	51 (63.0)	47 (62.7)	0.002	0.970
Gastric body
Yes	64	35 (43.2)	29 (38.7)	0.332	0.564
No	92	46 (56.8)	46 (61.3)	0.332	0.564
Gastric antrum
Yes	36	17 (21.0)	19 (25.3)	0.414	0.520
No	120	64 (79.0)	56 (74.7)	0.414	0.520
Tumor size^c (cm)
< 5	76	43 (59.7)	33 (55.0)	0.299	0.585
≥ 5	56	29 (40.3)	27 (45.0)	0.299	0.585
Histological type^c
Differentiated	52	28 (35.4)	24 (64.6)	0.002	0.962
Poorly-differentiated	94	51 (38.5)	43 (64.2)	0.002	0.962
Invasion^c
Yes	112	55 (76.4)	57 (89.1)	3.745	0.053
No	24	17 (23.6)	7 (10.9)	3.745	0.053
Lymph node metastasis^c
Yes	100	55 (76.4)	45 (70.3)	0.643	0.423
No	36	17 (23.6)	19 (29.7)	0.643	0.423
Relapse
Yes	98	58 (28.4)	40 (46.7)	5.566	0.018
No	58	23 (71.6)	35 (53.3)	5.566	0.018
Pathological grade
1	2	1 (1.3)	1 (1.3)	2.976	0.395
2	27	18 (22.2)	9 (12.0)
3	92	44 (54.3)	48 (64.0)
4	35	18 (22.2)	17 (22.7)
Tumor stage
I	14	9 (11.1)	5 (6.7)	2.129^a	0.546
II	22	12 (14.8)	10 (13.3)
III	102	49 (60.5)	53 (70.7)
IV	18	11 (13.6)	7 (9.3)

^acmh2 χ²-test;

^bTwo cases of gastric cancer involving gastric cardia and body;

^cMissed cases.

Table 2 Distribution of demographic and clinical characteristics in group II

Demographic and clinical features	n	Frequency of CIK cells immunotherapy, n (%)				χ²	P
Demographic and clinical features		0	1-10	11-25	> 25
Sex
Men	122	62 (76.5)	39 (84.8)	13 (86.7)	8 (57.1)	5.573	0.134
Women	34	19 (23.5)	7 (15.2)	2 (13.3)	6 (42.9)
Age (yr)
≤ 45	14	7 (8.6)	5 (10.9)	1 (6.6)	1 (7.1)	1.153	0.979
45 < age ≤ 60	71	36 (44.4)	20 (43.5)	7 (46.7)	8 (57.1)
> 60	71	38 (47.0)	21 (45.6)	7 (46.7)	5 (35.8)
Tumor site^a
Gastric cardia
Yes	58	30 (37.0)	17 (37.0)	5 (33.3)	6 (42.9)	0.290	0.962
No	98	51 (63.0)	29 (63.0)	10 (66.7)	8 (57.1)
Gastric body
Yes	64	35 (43.2)	19 (41.3)	5 (33.3)	5 (35.7)	0.691	0.875
No	92	46 (56.8)	27 (58.7)	10 (66.7)	9 (64.3)
Gastric antrum
Yes	36	17 (21.0)	10 (21.7)	4 (26.7)	5 (35.7)	1.614	0.656
No	120	64 (79.0)	36 (78.3)	11 (73.3)	9 (64.3)
Tumor size^c (cm)
< 5	76	43 (59.7)	17 (45.9)	7 (58.3)	9 (81.8)	4.834	0.184
≥ 5	56	29 (40.3)	20 (54.1)	5 (41.7)	2 (18.2)
Histological type^c
Differentiated	52	28 (35.4)	12 (30.0)	6 (40.0)	6 (50.0)	1.760	0.624
Poorly-differentiated	94	51 (64.6)	28 (70.0)	9 (60.0)	6 (50.0)
Invasion^c
Yes	112	55 (76.4)	38 (90.5)	10 (90.9)	9 (81.8)	4.226	0.238
No	24	17 (23.6)	4 (9.5)	1 (9.1)	2 (18.2)
Lymph node metastasis^c
Yes	100	55 (76.4)	31 (75.6)	7 (58.3)	7 (63.6)	2.371	0.499
No	36	17 (23.6)	10 (24.4)	5 (41.7)	4 (36.4)
Relapse
Yes	98	58 (71.6)	31 (67.4)	8 (53.3)	1 (7.1)	15.633	0.0004
No	58	23 (28.4)	15 (32.6)	7 (46.7)	13 (92.9)
Pathological grade
1	2	1 (1.2)	1 (2.2)	0 (0.0)	0 (0.0)	2.976^b	0.3953
2	27	18 (22.2)	8 (17.4)	0 (0.0)	1 (7.1)
3	92	44 (54.3)	25 (54.4)	12 (80.0)	11 (78.6)
4	35	18 (22.2)	12 (26.0)	3 (20.0)	2 (14.3)
Tumor stage
I	14	9 (11.1)	3 (6.5)	0 (0.0)	2 (14.2)	13.66^b	0.0386
II	22	23 (28.4)	3 (6.5)	1 (6.7)	6 (42.9)
III	102	38 (46.9)	34 (73.9)	13 (86.7)	6 (42.9)
IV	18	11 (13.6)	6 (13.1)	1 (6.6)	0 (0.0)

^aTumor sites in some cases were repeated;

^bBecause the theoretical value is less than 1, χ² was performed for patients who received cytokine-induced killer (CIK) cells immunotherapy at the frequencies of 11-25 and > 25, and for those who underwent CIK cells immunotherapy at the frequencies of 1-10, 11-25 and > 25;

^cMissed cases.

Table 3 Two- and five-year survival rates of gastric cancer patients in two groups

Groups	Survival rate (%)	95% CI	u-value	P
2-yr
Chemotherapy	52.6	41.7-63.6	2.721	0.007
CIK treatment	73.5	63.3-83.7
5-yr
Chemotherapy	23.9	13.5-34.3	1.913	0.0526
CIK treatment	40.4	27.1-53.7

CIK: Cytokine-induced killer; 95% CI: 95% confidence interval.

Table 4 First stage time-dependent multivariate Cox model analysis of cytokine-induced killer cells immunotherapy at different frequencies and prognosis of the patients¹^,² (n = 154³)

Variables⁴	β	s_β	Wald-χ²	P-value	HR	95% CI
No. of CIK infusion	-0.620	0.200	9.592	0.002	0.54	0.36-0.80
Sex	0.294	0.298	0.969	0.325	1.34	0.75-2.41
Age	0.508	0.200	6.492	0.011	1.66	1.12-2.46
Tumor stages	0.739	0.202	13.377	0.0003	2.10	1.40-3.11
Relapse (yes or no)	3.363	0.719	21.848	< 0.0001	28.87	7.05-118.25

¹>All patients with survival time of longer than 36 mo (median value for total patients) were defined as the survivors;

²Pearson correlation test between Schoenfeld residual of cytokine-induced killer (CIK) cells immunotherapy frequency and survival time (r = 0.01, F = 0.01, P = 0.936);

³Missed patients;

⁴Variable value definition in the Cox model (frequency of CIK cells immunotherapy: 0 = 0 time, 1 = 1-10 times, 2 = 11-25 times, 3 = more than 25 times; Sex: 1 = man, 2 = woman), age (0 = ≤ 45 yr, 1 = about 60 yr, 2 = over 60 yr), tumor stage (0 = stage I, 1 = stage II, 2 = stage III, 3 = stage IV), relapse (1 = yes, 0 = no). HR: Hazard risk; 95% CI: 95% confidence interval.

Table 5 Second stage time-dependent multivariate Cox model analysis of cytokine-induced killer cells immunotherapy at different frequencies and prognosis of patients¹^,² (n = 56)

Variables³	β	s_β	Wald-χ²	P-value	HR	95% CI
Number of CIK infusion	0.089	0.280	0.102	0.750	1.09	0.63-1.89
Sex	0.676	0.619	1.191	0.275	1.97	0.58-6.62
Age	-0.318	0.442	0.518	0.472	0.73	0.31-1.73
Tumor stages	-0.471	0.341	1.909	0.167	0.62	0.32-1.22
Relapse (yes or no)	2.203	0.558	15.582	< 0.0001	9.05	3.03-27.02

¹This model only involving the patients with a survival time longer than 36 mo. The survival rate of each patient was similar;

²Pearson correlation test between Schoenfeld residual of cytokine-induced killer (CIK) cells immunotherapy frequency and survival time (r = 0.307, F = 1.98, P = 0.176);

³Variable value definition in the Cox model (frequency of CIK cells immunotherapy: 0 = 0 time, 1 = 1-10 times, 2 = 11-25 times, 3 = more than 25 times; Sex: 1 = man, 2 = woman), age (0 = ≤ 45 yr, 1 = about 60 yr, 2 = over 60 yr), tumor stage (0 = stage I, 1 = stage II, 2 = stage III, 3 = stage IV), relapse (1 = yes, 0 = no). HR: Hazard risk; 95% CI: 95% confidence interval.

Citation: Jiang JT, Shen YP, Wu CP, Zhu YB, Wei WX, Chen LJ, Zheng X, Sun J, Lu BF, Zhang XG. Increasing the frequency of CIK cells adoptive immunotherapy may decrease risk of death in gastric cancer patients. World J Gastroenterol 2010; 16(48): 6155-6162
URL: https://www.wjgnet.com/1007-9327/full/v16/i48/6155.htm
DOI: https://dx.doi.org/10.3748/wjg.v16.i48.6155