Tumor cells PD-L1 expression as a favorable prognosis factor in nasopharyngeal carcinoma patients with pre-existing intratumor-infiltrating lymphocytes

Figures & data

Table 1. Association between PD-L1 expression and clinicopathological features of nasopharyngeal carcinoma patients (N = 209)

		PD-L1 expression
Feature	No. of patients	Tumor cells^pos	Tumor cells^neg	p value	Immune cells^pos	Immune cells^neg	p value
Gender
Female	59 (28.2%)	20 (33.9%)	39 (66.1%)	0.792	34 (34.7%)	25 (65.3%)	0.051
Male	150 (71.8%)	48 (32%)	102 (68%)		64 (22.5%)	86 (77.5%)
Age (years)
≤ 45	89 (42.6%)	30 (33.7%)	59 (66.3%)	0.755	48 (53.9%)	41 (46.1%)	0.079
> 45	120 (57.4%)	38 (31.7%)	82 (68.3%)		50 (41.7%)	70 (58.3%)
T classification
T1	26 (12.5%)	10 (38.5%)	16 (61.5%)	0.493	11 (42.3%)	15 (57.7%)	0.161
T2	68 (32.5%)	22 (32.4%)	46 (67.6%)		38 (55.9%)	30 (44.1%)
T3	69 (33.0%)	25 (36.2%)	44 (63.8%)		33 (47.8%)	36 (52.2%)
T4	46 (22.0%)	11 (23.9%)	35 (76.1%)		16 (34.8%)	30 (65.2%)
N classification
N0	40 (19.1%)	15 (37.5%)	25 (62.5%)	0.767	22 (55.0%)	18 (45.0%)	0.122
N1	96 (45.9%)	29 (30.2%)	67 (69.8%)		37 (38.5%)	59 (61.5%)
N2	51 (24.4%)	18 (35.3%)	33 (64.7%)		29 (56.9%)	22 (43.1%)
N3	22 (10.5%)	6 (27.3%)	16 (72.7%)		10 (45.5%)	12 (54.5%)
M classification
M0	158 (75.6%)	55 (34.8%)	103 (65.2%)	0.217	78 (49.4%)	80 (50.6%)	0.207
M1	51 (24.4%)	13 (25.5%)	38 (74.5%)		20 (39.2%)	31 (60.8%)
Clinical stage
I	10 (4.8%)	6 (60.0%)	4 (40.0%)	0.034	5 (50.0%)	5 (50.0%)	0.195
II	55 (26.3%)	15 (27.3%)	40 (72.7%)		26 (47.3%)	29 (52.7%)
III	83 (39.7%)	33 (39.8%)	50 (60.2%)		45 (54.2%)	38 (45.8%)
IV	61 (29.2%)	14 (23.0%)	47 (77.0%)		22 (36.1%)	39 (63.9%)
Treatment
1	42 (20.1%)	11 (26.2%)	31 (73.8%)	0.154	15 (35.7%)	27 (64.3%)	0.091
2	88 (42.1%)	25 (28.4%)	63 (71.6%)		39 (44.3%)	49 (55.7%)
3	79 (37.8%)	32 (40.5%)	47 (59.5%)		44 (55.7%)	35 (44.3%)
Histological differentiation
U	54 (25.8%)	21 (38.9%)	33 (61.1%)	0.247	30 (55.6%)	24 (44.4%)	0.138
D	155 (74.2%)	47 (30.3%)	108 (69.7%)		68 (43.9%)	87 (56.1%)
Peritumoral CD3 expression
Low	105 (50.2%)	15 (14.3%)	90 (85.7%)	< 0.001	32 (69.5%)	73 (30.5%)	< 0.001
High	104 (49.8%)	53 (51.0%)	51 (49.0%)		66 (63.5%)	38 (36.5%)
Intratumoral CD3 expression
Low	105 (50.2%)	18 (17.1%)	87 (82.9%)	< 0.001	38 (36.2%)	67 (63.8%)	0.002
High	104 (49.8%)	50 (48.1%)	54 (51.9%)		60 (57.7%)	44 (42.3%)
Vital status
Alive	130 (49.3%)	49 (37.7%)	81 (62.3%)	0.041	65 (50.0%)	65 (50.0%)	0.248
Dead	79 (50.7%)	19 (24.1%)	60 (75.9%)		33 (41.8%)	46 (58.2%)

PD-L1, Programmed death ligand 1.

Figure 1. Evaluation of CD3, PD-L1 protein and their associations in nasopharyngeal carcinoma patients. Tumor and immune cell PD-L1 protein (A) and intratumoral and peritumoral CD3⁺ lymphocytes (B). Correlation between intratumoral (C) or peritumoral CD3⁺ lymphocytes and TCs-PD-L1 (D), and correlation between intratumoral (E) or peritumoral CD3⁺ lymphocytes (F) and ICs- PD-L1 expression.

Table 2. Cox proportional regression analysis for the prediction of nasopharyngeal patient OS and DFS

	Univariate analysis
	OS		DFS
Covariant	HR (95% CI)	p	HR (95% CI)	`p
Age (< 50 vs. ≥ 50)	0.768 (0.494–1.194)	0.241	0.742 (0.489–1.128)	0.162
Gender (Female vs. Male)	0.863 (0.534–1.394)	0.547	0.798 (0.509–1.251)	0.326
T classification (T1 vs. T2 vs. T3 vs.T4)	1.774 (1.372–2.294)	< 0.001	1.765 (1.381–2.256)	< 0.001
N classification (N0 vs. N1 vs. N2 vs. N3)	1.660 (1.302–2.117)	< 0.001	1.686 (1.339–2.123)	< 0.001
M classification (M0 vs. M1)	2.783 (1.769–4.379)	< 0.001	2.660 (1.715–4.125)	< 0.001
Clinical stage (I vs. II vs. III vs. IV)	3.106 (1.679–5.746)	< 0.001	2.339 (1.742–3.141)	< 0.001
Histological differentiation (U vs. D)	1.727 (0.969–3.078)	0.064	1.481 (0.882–2.489)	0.138
Treatment (1 vs. 2 vs. 3)	0.571 (0.424–0.770)	< 0.001	0.565 (0.425–0.750)	< 0.001
CD3 in total (High vs. Low)	0.741 (0.475–1.156)	0.186	0.730 (0.479–1.112)	0.143
Intratumoral CD3 (High vs. Low)	0.545 (0.346–0.859)	0.009	0.522 (0.339–0.804)	0.003
Peritumoral CD3 (High vs. Low)	1.141 (0.734–1.774)	0.559	1.094 (0.720–1.662)	0.673
ICs-PD-L1 (Postive vs. Negative)	0.585 (0.309–1.106)	0.099	0.571 (0.311–1.051)	0.072
TCs-PD-L1 (Postive vs. Negative)	0.563 (0.335–0.945)	0.030	0.597 (0.369–0.964)	0.035
Type in total CD3 (I vs. II vs. III vs. IV)	1.143 (0.942–1.386)	0.176	1.122 (0.934–1.348)	0.220
Type in intratumoral CD3 (I vs. II vs. III vs. IV)	1.220 (1.008–1.478)	0.041	1.180 (0.983–1.416)	0.046
	Multivariate analysis
	OS		DFS
Covariant	HR (95% CI)	p	HR (95% CI)	p
T classification (T1 vs. T2 vs. T3 vs.T4)	1.121 (0.820–1.531)	0.475	1.113 (0.810–1.528)	0.509
N classification (N0 vs. N1 vs. N2 vs. N3)	1.048 (0.772–1.422)	0.763	0.982 (0.714–1.351)	0.912
M classification (M0 vs. M1)	0.756 (0.377–1.516)	0.431	0.673 (0.318–1.425)	0.301
Clinical stage (I vs. II vs. III vs. IV)	2.412 (1.270–4.582)	0.007	2.823 (1.417–5.625)	0.003
Treatment (1 vs. 2 vs. 3)	0.447 (0.321–0.622)	< 0.001	0.444 (0.314–0.629)	< 0.001
Intratumoral CD3 (High vs. Low)	0.607 (0.371–0.995)	0.084	0.624 (0.366–1.063)	0.083
TCs-PD-L1 (Postive vs. Negative)	1.116 (0.647–1.924)	0.693	1.037 (0.583–1.845)	0.900
Type in intratumoral CD3 (I vs. II vs. III vs. IV)	1.387 (1.074–1.790)	0.012	1.465 (1.113–1.928)	0.006

TCs-PD-L1, Tumor Cells Programmed death ligand 1; ICs-PD-L1, Immune Cells Programmed death ligand 1.

Figure 2. Survival curves of different distributions of CD3⁺ TILs. Kaplan–Meier plots of OS (A) and DFS (B) according to the percentage of TILs. OS (C and E) and DFS (D and F) based on intratumoral and peritumoral CD3⁺ lymphocytes.

Figure 3. Survival curves of different distributions of PD-L1+ cells. The present study analyzed OS (A and C) and DFS (B and D) based on TCs-PD-L1 and ICs-PD-L1.

Figure 4. Comparison of survival according to staging system in 209 NPC patients. OS and DFS analyses according to the stage classification based on CD3⁺ lymphocytes and TCs-PD-L1 (A and B). Survival analysis based on intratumoral CD3⁺ lymphocytes and TCs-PD-L1 (C and D).