Efficacy of adjuvant cytokine-induced killer cell immunotherapy in patients with colorectal cancer after radical resection

Figures & data

Table 1. Baseline characteristics of patients with colorectal cancer

Characteristic	Total	Control group	CIK group	P
No. of patients	122	62	60
Sex				0.536
Male	78	38	40
Female	44	24	20
Age (years)				0.606
≥ 60	34	16	18
< 60	88	46	42
Primary tumor				0.498
Rectum	43	24	19
Left-sided colon	46	24	22
Right-sided colon	33	14	19
Histology				1.000^a
Well differentiated	9	5	4
Moderate differentiated	84	42	42
Poorly differentiated	29	15	14
T stage				0.597^a
T1 + T2	8	3	5
T3	65	32	33
T4	49	27	22
N stage				0.186
N0	33	20	13
N1	65	28	37
N2	24	14	10
TNM stage^b				0.021^a
II	32	21	11
III	86	41	45
IV	4	0	4
Tumor size (cm)				0.161
< 4	34	17	17
≥ 4	38	15	23
Missing data	50	30	20
Neural invasion				0.520
Absent	91	48	43
Present	15	8	7
Missing data	16	6	10
Venous invasion				0.452
Absent	78	40	38
Present	28	16	12
Missing data	16	6	10
MMR status				0.519^a
dMMR	3	1	2
pMMR	34	15	19
Missing data	85	46	39
Chemotherapy regimen				0.371^a
FOLFOX	31	19	12
CAPOX	81	39	42
Capecitabine	10	4	6
Duration of chemotherapy				0.252
> 20 weeks	73	34	39
< 20 weeks	49	28	21
Adjuvant radiotherapy				0.504
Yes	12	5	7
No	110	57	53
Neoadjuvant chemotherapy				0.145
Yes	18	12	6
No	104	50	54
Neoadjuvant radiotherapy				0.373
Yes	11	7	4
No	111	55	56

CIK, cytokine-induced killer cell. CAPOX, Capecitabine + Oxaliplatin. FOLFOX, Oxaliplatin + 5-fluorouracil. MMR, mismatch repair; dMMR, MMR-defcient; pMMR, MMR-profcient.

a, Fisher’s exact test. b, According to the 8th edition of the American Joint Committee on Cancer staging system.

Figure 1. Phenotypic analysis of CIK cells after expansion. (a) The phenotype of autologous CIK cells after 14-d culture from 51 patients was evaluated using flow cytometry. The positive proportions of CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺, CD3⁻CD56⁺, and CD3⁺CD56⁺ are shown. (b) The phenotypic evolution of CIK cells after culture for first four treatment cycles. The results were from 49 patients and are represented as mean ± SEM. NS, not significant. * p < .05

Figure 2. Kaplan–Meier estimates of disease-free survival (DFS) (a) and overall survival (OS) (b) of patients with CRC by treatment group. Significantly improved DFS and OS were observed in the CIK group (n = 60) versus the control group (n = 62)

Table 2. Univariate and multivariate analysis of disease-free survival in patients with CRC

	Univariate analysis		Multivariate analysis
Variables	HR (95% CI)	P	HR (95% CI)	P
Sex (male vs. female)	1.581 (0.832–3.004)	0.162
Age (≥ 60 vs. < 60)	1.158 (0.618–2.171)	0.647
Primary tumor (right- vs. left-sided colon vs. rectum)	1.072 (0.745–1.543)	0.707
Histology (poorly vs. well/moderate)	1.000 (0.518–1.931)	0.999
T stage (4 vs. 3, 2, 1)	2.014 (1.127–3.599)	0.018^a	2.139 (1.192–3.838)	0.011^a
N stage (2 vs. 1 vs. 0)	1.387 (0.900–2.138)	0.139
TNM stage (III, IV vs. II)	1.357 (0.689–2.672)	0.378
Chemotherapy regimen (CAPOX, Capecitabine vs. FOLFOX)	0.688(0.372–1.273)	0.234
Duration of chemotherapy (> 20 weeks vs. < 20 weeks)	0.556(0.312–0.992)	0.047^a	0.566 (0.317–1.013)	0.055
Treatment (CIK vs. control)	0.399 (0.215–0.741)	0.004^a	0.399 (0.214–0.743)	0.004^a

HR, Hazard ratio; CI, confidence interval; CRC, colorectal cancer; CAPOX, Capecitabine + Oxaliplatin; FOLFOX, Oxaliplatin + 5-fluorouracil; CIK, cytokine-induced killer cell.

^aP value < 0.05

Table 3. Univariate and multivariate analysis of overall survival in patients with CRC

	Univariate analysis		Multivariate analysis
Variables	HR (95% CI)	P	HR (95% CI)	P
Sex (male vs. female)	1.471 (0.607–3.565)	0.393
Age (≥ 60 vs. < 60)	0.918 (0.364–2.316)	0.857
Primary tumor (right- vs. left-sided colon vs. rectum)	0.747 (0.440–1.268)	0.280
Histology (poorly vs. well/moderate)	1.738 (0.760–3.974)	0.190
T stage (4 vs. 3, 2, 1)	1.770(0.792–3.954)	0.164
N stage (2 vs. 1 vs. 0)	1.351 (0.755–2.415)	0.311
TNM stage (III, IV vs. II)	1.350 (0.551–3.304)	0.511
Chemotherapy regimen (CAPOX, Capecitabine vs. FOLFOX)	0.631(0.270–1.474)	0.287
Duration of chemotherapy (> 20 weeks vs. < 20 weeks)	0.469 (0.208–1.057)	0.068	0.535 (0.236–1.211)	0.133
Treatment (CIK vs. control)	0.308 (0.122–0.776)	0.013^a	0.334 (0.132–0.846)	0.021^a

HR, Hazard ratio; CI, confidence interval; CRC, colorectal cancer; CAPOX, Capecitabine + Oxaliplatin; FOLFOX, Oxaliplatin + 5-fluorouracil; CIK, cytokine-induced killer cell.

^aP value < 0.05

Figure 3. Subgroup analysis to estimate the survival benefits from sequential CIK cell immunotherapy according to the T stage. (a) Sequential CIK cell immunotherapy slightly prolonged the disease-free survival (DFS) and overall survival (OS) of patients with T1-3 stage disease. (b) Sequential CIK cell immunotherapy significantly improved the DFS and OS of patients with T4 stage disease

Figure 4. Subgroup analysis to estimate the survival benefits from sequential CIK cell immunotherapy according to the duration of chemotherapy. (a) Sequential CIK cell immunotherapy significantly prolonged the disease-free survival (DFS) and overall survival (OS) of patients receiving less than 20 weeks of chemotherapy. (b) Sequential CIK cell immunotherapy slightly prolonged the DFS and OS of patients receiving more than 20 weeks of chemotherapy