Table 3.

Hazard ratios (HR) and 95% confidence intervals (CI) for CRC-specific death in relation to tumor composite scores for cytotoxic T lymphocytes (CTL) and granzyme B (GZMB) in the CRC patients, IWHS, 1986-2011.

Composite score	CRC-specific death
	No. deaths b	Person-years	HR (95% CI)c	HR (95% CI)d	HR (95% CI)e	HR (95% CI)f
CTLa	n=144
2-3.8	50	745	Reference	Reference	Reference	Reference
4-5.1	50	1089	0.73 (0.49-1.08)	0.63 (0.42-0.94)	0.67 (0.43-1.04)	0.68 (0.45-1.02)
5.2-6.3	23	1040	0.36 (0.22-0.59)	0.41 (0.25-0.67)	0.40 (0.23-0.72)	0.49 (0.29-0.82)
>6.3	21	1017	0.33 (0.20-0.55)	0.30 (0.18-0.51)	0.30 (0.15-0.57)	0.44 (0.23-084)
P-trend			<0.0001	<0.0001	<0.0001	0.003
GZMB a	n=144
2	83	1518	Reference	Reference	Reference	Reference
2.2-2.8	46	744	0.71 (0.47-1.08)	0.79 (0.52-1.21)	0.69 (0.43-0.10)	0.86 (0.56-1.33)
>3	15	1544	0.37 (0.25-0.56)	0.41 (0.27-0.63)	0.44 (0.26-0.75)	0.60 (0.35-1.03)
P-trend			0.0001	0.0001	0.002	0.06
Joint score for CTL and GZMB g	n=144
0	40	500	Reference	Reference	Reference
1	87	2443	0.48 (0.33-0.71)	0.55 (0.37-0.79)	0.59 (0.39-0.89)
2	17	825	0.27 (0.15-0.48)	0.27 (0.15-0.49)	0.27 (0.13-0.54)
P-trend			<0.0001	<0.0001	0.0001

^aTumor CTL and GZMB composite scores were created as a sum of corresponding epithelial and stromal scores categorized into quartiles for CTL and tertiles for GZMB.

^bThe number of deaths is slightly different in the analyses of CTL and GZMB because of different number of available cores (n=465 for CTL and n=458 for GZMB; overall 468 CRC patients had tissues immunostained for CTL or GZMB).

^cModel 1: Unadjusted.

^dModel 2: Model adjusted for age at diagnosis, BMI, smoking status, stage and grade at diagnosis.

^eModel 3: Model 2 + integrated pathway.

^fBoth GZMB and CTL tumor composite scores were included with all variables in Model 2.

^gJoint score for GZMB and CTL tumor composite scores was created as follows: 0 – lowest categories of CTL and GZMB; 2 – highest categories of CTL and GZMB; and 1 – all other combinations.