CD3-CD8 immune score associated with a clinical score stratifies PDAC prognosis regardless of adjuvant or neoadjuvant chemotherapy

Figures & data

Table 1. Demographic and clinical characteristics of the two cohorts.

Variable	Cohorte1, N = 205^1	Cohorte2, N = 129^1	p-value^2
Sex			.6
F	103 (50%)	61 (47%)
M	101 (50%)	68 (53%)
NA	1	0
Age	67 (40, 86)	70 (46.8, 85.2)	.020
NA	1	1
Neoadjuvant treatment			<.001
No	194 (95%)	85 (67%)
Yes	10 (4.9%)	42 (33%)
NA	1	2
Adjuvant treatment			.068
No	46 (24%)	15 (15%)
Yes	146 (76%)	86 (85%)
NA	13	28
Resection			.081
R0	161 (80%)	81 (72%)
R1	37 (18%)	32 (28%)
R2	2 (1.0%)	0 (0%)
NA	5	16
Histological grade			.4
Well differentiated	42 (21%)	27 (23%)
Moderatly differentiated	125 (61%)	67 (58%)
Poorly differentiated	32 (16%)	21 (18%)
Mucinous differentiated	5 (2.5%)	0 (0%)
NA	1	14
Tumor status (AJCC 2017)			<.001
1	24 (14%)	10 (8.1%)
2	110 (64%)	52 (42%)
3	39 (23%)	56 (45%)
4	0 (0%)	6 (4.8%)
NA	32	5
Node status (AJCC 2017)			.6
0	49 (24%)	35 (29%)
1	83 (41%)	47 (39%)
2	72 (35%)	40 (33%)
NA	1	7

^aMedian (min,max); n (%).

^bWilcoxon rank sum test; Pearson’s Chi-squared test; Fisher’s exact test.

Figure 1. Description of PDAC immune populations and their associated prognostic value.

Representative images of PDAC infiltrates (left panel) and their detection using QuPath (right panel). Scale bar is 200 µm (a). Kaplan-Meier survival curves for overall survival (OS) according to CD3-IM (b), CD3-TC (c), CD8-IM (d) and CD8-TC (e). Log-rank test; HR = hazard ratio, 95% CI in square brackets.

Figure 2. Immune score combining CD3 and CD8 IHC markers is associated with PDAC prognosis.

(a) Graphical abstract showing immune score generation. Kaplan-Meier curves for the immune score (IS) in 5 modalities (score 0 to 4) in terms of OS (b) and PFS (c) in the training dataset. Kaplan-Meier curves for low (0–2) vs high (3–4) immune score in terms of OS (d) and PFS (e) in the training dataset. Log-rank test; HR = hazard ratio, 95% CI in square brackets.

Table 2. Univariate and multivatiate Cox models for overall survival in the whole cohort (complete data for n = 280 patients).

Variables	Univariate			Multivariate
	HR	95% CI	p-value	HR	95% CI	p-value
Adjuvant therapy
No	—	—		—	—
Yes	0.61	0.44, 0.84	.003	0.49	0.35, 0.69	<.001
Histological Grade
Well	—	—		—	—
Moderatly	1.23	0.86, 1.77	.3	1.21	0.84, 1.75	.3
Poorly	2.65	1.68, 4.20	<.001	2.50	1.57, 3.98	<.001
Mucinous	4.34	1.54, 12.2	.005	5.42	1.84, 16.0	.002
Sex
Female	—	—		—	—
Male	0.80	0.60, 1.05	.10	0.72	0.55, 0.96	.023
Node status (AJCC 2017)
0	—	—		—	—
1	1.36	0.95, 1.97	.10	1.73	1.18, 2.54	0.005
2	2.22	1.53, 3.22	<.001	2.33	1.57, 3.44	<.001
Immune Score (IS)
Low	—	—		—	—
High	0.60	0.45, 0.80	<.001	0.60	0.44, 0.81	<.001

HR : Hazard Ratio ; CI : Confidence Interval.

Table 3. Univariate and multivatiate Cox models for progression-free survival in the whole cohort (complete data for n = 273 patients).

Variables	Univariate			Multivariate
	HR^1	95% CI^1	p-value	HR^1	95% CI^1	p-value
Adjuvant therapy
No	—	—		—	—
Yes	0.69	0.51, 0.94	.020	0.61	0.44, 0.85	.003
Histological Grade
Well	—	—		—	—
Moderatly	1.10	0.79, 1.53	.6	1.16	0.83, 1.62	.4
Poorly	2.30	1.50, 3.52	<.001	2.14	1.39, 3.28	<.001
Mucinous	4.78	1.71, 13.4	.003	6.13	2.14, 17.5	<.001
Sex
Female	—	—		—	—
Male	0.87	0.67, 1.12	.3	0.80	0.61, 1.04	.091
Node status (AJCC 2017)
0	—	—		—	—
1	1.19	0.85, 1.66	.3	1.51	1.06, 2.15	.021
2	1.84	1.31, 2.59	<.001	2.10	1.47, 3.01	<.001
Immune Score (IS)
Low	—	—		—	—
High	0.54	0.40, 0.74	<.001	0.56	0.40, 0.76	<.001

HR : Hazard Ratio ; CI : Confidence Interval.

Figure 3. Improved prognostic value for PDAC outcome with a combination of clinical features and immune score.

Kaplan-Meier curves for low vs high clinical score in the training (a) and validation datasets (b) in terms of OS. Kaplan-Meier curves for low vs high combined (clinical + immune) score in the training (c) and validation datasets (d) in terms of OS. AUC for predictive value of the different models (e). Log-rank test; HR = hazard ratio, 95% CI in square brackets.

Figure 4. Combined score associating immune score and clinical score is associated with PDAC prognosis regardless of neoadjuvant or adjuvant chemotherapy.

Kaplan-Meier curves for low vs high immune score (IS) in patients with adjuvant chemotherapy (a) and in patients with neoadjuvant chemotherapy (b) in the training dataset in terms of OS. Kaplan-Meier curves for low vs high combined score in patients with adjuvant chemotherapy (c) and in patients with neoadjuvant chemotherapy (d) in the training dataset in terms of OS.

Data availability statement

Date are available on reasonable request.