Analysis of PD1, PDL1, PDL2 expression and T cells infiltration in 1014 gastric cancer patients

Figures & data

Table 1. Clinicopathological and molecular features according to PDL1 expression.

		PDL1 in tumor			PDL1 in immune cells
	n	Pos(%)	Neg(%)	p-value	Pos(%)	Neg(%)	p-value
Gender	1014			0.140			0.437
female	275	41.5	58.5		73.1	26.9
male	739	36.4	63.6		75.5	24.5
Age	1014			0.507			0.405
< = 60	506	36.8	63.2		73.7	26.3
>60	508	38.8	61.2		76.0	24.0
Localization	971			0.760			0.342
Upper	239	38.5	61.5		17.6	6.0
Middle	259	35.9	64.1		79.9	20.1
Lower	468	39.1	60.9		72.6	27.4
whole	5	40.0	60.0		60.0	40.0
Lauren type	995			0.013			0.247
Diffuse	242	32.2	67.8		72.3	27.7
Intestinal	569	38.0	62.0		74.9	25.1
Mixed	184	46.2	53.8		79.3	20.7
T stage	1014			0.068			0.027
T1	64	37.5	62.5		82.8	17.2
T2	124	49.2	50.8		83.1	16.9
T3	651	36.3	63.7		72.8	27.2
T4	175	35.4	64.6		73.7	26.3
N stage	1007			<0.001			0.016
N0	252	43.7	56.3		75.8	24.2
N+	755	38.4	61.57%		77.2	22.8
M stage	979			0.028			0.002
M0	913	38.4	61.6		75.9	24.1
M1	66	25.8	74.2		59.1	40.9
pTNM	979			<0.001			0.003
1	118	44.1	55.9		80.5	19.5
2	280	44.6	55.4		77.9	22.1
3	515	33.8	66.2		73.8	26.2
4	66	25.8	74.2		59.1	40.9
Vascular invasion	999			0.215			0.114
neg	456	39.9	60.1		77.6	22.4
pos	543	36.1	63.9		73.3	26.7
Diameter	978			0.973			<0.001
<5cm	520	37.9	62.1		80.2	19.8
> = 5cm	458	38.0	62.0		70.1	29.9
Differentiation	962			0.115			0.873
well	23	21.7	78.3		69.6	30.4
poorly	470	40.6	59.4		76.0	24.0
moderately	469	37.1	62.9		76.1	23.9
MMR	857			0.999			0.057
deficient	142	40.8	59.2		69.7	30.3
proficient	715	40.8	59.2		77.2	22.8
EBV status	967			<0.001			0.001
neg	933	36.5	63.5		74.2	25.8
pos	34	76.5	23.5		100.0	0.0
c-Met status	979			<0.001			<0.001
neg	655	33.0	67.0		71.1	28.9
pos	324	48.1	51.9		83.6	16.4
PCNA	892			<0.001			<0.001
1	28	10.7	89.3		57.1	42.9
2	104	31.7	68.3		61.5	38.5
3	760	40.5	59.5		78.4	21.6

Figure 1. PDL1, PDL2, PD1, CD3 and CD8 expression in gastric carcinoma by immunohistochemistry (× 200). PDL1 expression was evaluated based on staining in the cytoplasm and membrane of tumor cells and immune cells. A: Intense expression of PDL1 in tumor cells; B: Immune cells expressing PDL1 in the disseminated lymphocytes and macrophages; C: representative cytoplasmic expression of PDL2 in tumor tissues. D: PD1 expressed in the disseminated immune cells infiltrating the tumor tissues; E: The representative images of CD3⁺ T cells; F: The representative images of CD8+ T lymphocytes.

Table 2. Survival analysis of 1014 gastric cancers.

	Univariable				Multivariable
	p-value	HR	95%CI		p-value	HR	95%CI
Age	<0.001	1.022	1.013	1.030	<0.001	1.024	1.016	1.033
Vascular invasion
pos vs neg	<0.001	2.130	1.760	2.578	0.012	0.760	0.614	0.942
Lauren
Mixed	0.017				0.005	0.853	0.762	0.954
Diffused	0.061	1.141	0.994	1.311
Intestinal	0.008	0.850	0.753	0.959
pTNM
1	<0.001				<0.001
2	<0.001	3.093	1.764	5.426	<0.001	3.507	1.819	6.763
3	<0.001	7.354	4.302	12.572	<0.001	7.151	3.752	13.628
4	<0.001	23.786	13.208	42.834	<0.001	26.786	13.417	53.478
PDL1 TU
pos vs neg	<0.001	0.685	0.564	0.831	0.021	0.786	0.640	0.965
CD3	<0.001	0.974	0.963	0.985	<0.001	0.978	0.967	0.989

Figure 2. Kaplan-Meire curves stratified by PDL1, CD3, and CD8 expression. PDL1 expression in tumor cells predicted better survival in GC patients using cut-off value of IRS for 2 and 5 as 3 groups (A, PDL1TU: PDL1 expression in tumor cells) or in the immune cells (B, PDL1IM: PDL1 expression in immune cells). CD3⁺ (C) or CD8⁺ (D) T cells both associated with better outcome in a density dependent manner.

Figure 3. Prognostic significance of PDL1 expression (A) in tumor cells as well as the intersection of PDL1 expression and CD3⁺ T cell infiltration (B) in subgroups of different pTNM stages. Using the median of CD3 density as the cutoff value and PDL1 membrane expression in tumor cells, the patients were divided into 2 groups, one with CD3 density lower than median and PDL1 negative expression, and the other group consisted with the rest patients.

Figure 4. PDL1 expression associated with better outcome in the subgroup of EBV+ and EBV- GC patients (A). PDL1, PDL2, PD1, CD3 and CD8 expression in the identical EBV infected gastric cancer tissue (× 200, B). In situ hybridization of EBER (a) was shown in the identical patients together with PDL1 (b), PDL2 (c) and PD1 (d) expression in GC tumor tissues and CD3 (e) and CD8 (f) in intratumoral lymphocytes.