Prognostic Significance of Circulating Lymphocyte Subsets Before Treatment in Patients with Nasopharyngeal Carcinoma

Figures & data

Table 1 Baseline Characteristics of Patients (N =677)

Characteristics	No of Patients	Percent
Age (Years)
≤46	351	51.8
>46	326	48.2
Gender
Males	506	74.7
Females	171	25.3
Smoking
No	444	65.6
Yes	233	34.3
Family history of NPC
No	610	90.1
Yes	67	9.9
WHO pathologic classification
WHO II	74	10.9
WHO III	603	89.1
Primary tumor (T) stage
T1	32	4.7
T2	244	36
T3	256	37.8
T4	145	21.4
Regional lymph nodes (N) stage
N0	36	5.3
N1	326	48.2
N2	263	38.8
N3	52	7.7
Clinical stage
I	5	0.7
II	156	23
III	326	48.2
IVa	190	28.1
Treatment received by patients
Radiotherapy alone	35	5.2
CCRT	312	46.1
CCRT+IC	134	19.8
CCRT+AC	175	25.8
IC+CCRT+AC	21	3.1

Note: According to the AJCC 8th edition staging.

Abbreviations: NPC, nasopharyngeal carcinoma; CCRT, concurrent chemoradiotherapy; IC, induction chemotherapy; AC, adjuvant chemotherapy.

Table 2 Correlation of Circulating Lymphocyte Subsets with Clinical Variables

Clinical Variables	Circulating Lymphocyte Subsets
	CD3	CD4	CD8	CD4/CD8	CD19	NK
Sex	r =0.030	r =0.032	r =−0.021	r =0.037	r =0.087	r =−0.010
	P =0.439	P =0.399	P =0.592	P =0.342	P =0.024	P =0.800
Age	r =−0.160	r =0.049	r =−0.244	r =0.230	r =−0.053	r =0.129
	P <0.001	P =0.204	P <0.001	P <0.001	P =0.171	P =0.001
Pathology	r =0.056	r =0.033	r =0.070	r =−0.034	r =0.011	r =−0.076
	P =0.148	P =0.392	P =0.070	P =0.371	P =0.779	P =0.048
Tumor stage	r =−0.010	r =−0.011	r =−0.017	r =−0.017	r =−0.100	r =0.054
	P =0.794	P =0.783	P =0.660	P =0.662	P =0.010	P =0.163
Node stage	r =0.049	r =−0.002	r =0.038	r =−0.019	r =−0.171	r =−0.004
	P =0.203	P =0.966	P =0.328	P =0.621	P <0.001	P =0.922
Clinical stage	r =−0.014	r =−0.009	r =−0.016	r =0.019	r =−0.174	r =0.046
	P =0.719	P =0.818	P =0.676	P =0.630	P <0.001	P =0.234

Figure 1 ROC curves of CD19⁺ B cells based on overall survival (A), CD3⁺CD4⁺ T cells and CD19⁺ B cells based on progression-free survival (B), CD3⁺CD4⁺ T cells and CD4/CD8 ratio based on distant metastasis-free survival (C).

Figure 2 Kaplan–Meier survival curves of high and low CD19⁺ B cell groups based on overall survival (A), progression-free survival (B), locoregional relapse-free survival (C), distant metastasis-free survival (D) in NPC patients.

Figure 3 Kaplan–Meier survival curves of high and low CD3⁺CD4⁺ T cell groups based on overall survival (A), progression-free survival (B), locoregional relapse-free survival (C), distant metastasis-free survival (D) in NPC patients.

Figure 4 Kaplan–Meier survival curves of high and low CD4/CD8 radio groups based on overall survival (A), progression-free survival (B), locoregional relapse-free survival (C), distant metastasis-free survival (D) in NPC patients.

Table 3 Multivariate Cox Proportional Hazards Analysis of 677 Patients with NPC

Variable	OS				PFS
	Univariate		Multivariate		Univariate		Multivariate
	P	HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)
Sex	0.098	1.387(0.942–2.042)	0.006	1.797(1.185–2.725)	0.399	1.155(0.826–1.616)
Age	0.000	0.555(0.405–0.761)	0.003	0.618(0.449–0.850)	0.003	0.649(0.489–0.862)	0.012	0.691(0.517–0.923)
Smoking	0.219	1.220(0.888–1.675)			0.400	1.133(0.847–1.515)
Family history of NPC	0.179	0.657(0.356–1.212)			0.268	0.742(0.438–1.257)
Pathology	0.297	0.787(0.502–1.234)			0.302	0.804(0.532–1.216)
Tumor stage	0.000	0.392(0.272–0.566)	0.006	0.517(0.323–0.827)	0.000	0.443(0.321–0.610)	0.002	0.532(0.354–0.799)
Node stage	0.000	0.460(0.334–0.632)	0.001	0.545(0.379–0.786)	0.000	0.462(0.346–0.617)	0.000	0.497(0.354–0.698)
Clinical stage	0.000	0.297(0.175–0.506)	0.954	1.022(0.487–2.146)	0.000	0.327(0.206–0.519)	0.987	1.005(0.528–1.915)
NLR	0.009	0.658(0.481–0.900)	0.273	0.837(0.609–1.151)	0.010	0.689(0.519–0.914)	0.263	0.847(0.634–1.133)
Albumin	0.001	1.695(1.233–2.330)	0.017	1.509(1.076–2.116)	0.009	1.458(1.097–1.939)	0.035	1.393(1.024–1.895)
Hb	0.002	1.650(1.200–2.267)	0.003	1.704(1.196–2.427)	0.003	1.557(1.168–2.074)	0.018	1.435(1.065–1.933)
LDH	0.000	0.490(0.355–0.675)	0.000	0.493(0.355–0.684)	0.000	0.512(0.383–0.684)	0.000	0.540(0.401–0.729)
CD3^+ T cells	0.629	1.079(0.793–1.469)			0.437	1.118(0.844–1.480)
CD4^+ T cells	0.134	1.301(0.922–1.835)			0.016	1.481(1.076–2.038)	0.040	1.462(1.018–2.099)
CD8^+ T cells	0.417	0.880(0.647–1.198)			0.391	0.885(0.668–1.171)
CD4/CD8 ratio	0.104	1.291(0.949–1.757)			0.025	1.378(1.042–1.824)	0.125	1.283(0.933–1.764)
CD19^+ B cells	0.000	2.641(1.822–3.827)	0.000	2.147(1.468–3.139)	0.000	2.058(1.498–2.828)	0.001	1.736(1.251–2.409)
NK cells	0.596	0.920(0.676–1.252)			0.650	0.937(0.708–1.240)
Treatment	0.396	0.702(0.311–1.588)			0.287	0.664(0.312–1.412)
	LRFS				DMFS
	Univariate		Multivariate		Univariate		Multivariate
	P	HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)
Sex	0.798	1.097(0.539–2.232)			0.548	0.857(0.518–1.419)
Age	0.535	1.216(0.656–2.255)			0.690	0.912(0.580–1.434)
Smoking	0.190	0.621(0.305–1.265)			0.553	1.152(0.722–1.840)
Family history of NPC	0.640	1.250(0.491–3.187)			0.173	0.497(0.181–1.360)
Pathology	0.115	0.537(0.248–1.163)			0.423	1.406(0.610–3.239)
Tumor stage	0.323	0.727(0.387–1.368)			0.000	0.333(0.189–0.587)	0.005	0.363(0.178–0.738)
Node stage	0.245	0.698(0.381–1.280)			0.000	0.397(0.246–0.642)	0.004	0.446(0.259–0.768)
Clinical stage	0.191	0.582(0.258–1.310)			0.001	0.257(0.112–0.592)	0.963	1.027(0.328–3.215)
NLR	0.249	0.698(0.379–1.287)			0.416	0.828(0.526–1.304)
Albumin	0.970	1.012(0.552–1.854)			0.806	1.058(0.673–1.665)
Hb	0.323	1.361(0.738–2.510)			0.472	1.182(0.750–1.862)
LDH	0.901	0.962(0.525–1.764)			0.000	0.369(0.224–0.607)	0.002	0.444(0.269–0.733)
CD3^+ T cells	0.784	1.089(0.594–1.996)			0.480	1.178(0.748–1.856)
CD4^+ T cells	0.723	1.126(0.585–2.166)			0.000	3.716(1.852–7.457)	0.003	3.124(1.487–6.562)
CD8^+ T cells	0.881	0.955(0.521–1.749)			0.196	0.740(0.469–1.168)
CD4/CD8 ratio	0.575	1.189(0.649–2.180)			0.002	2.056(1.295–3.264)	0.225	1.359(0.828–2.230)
CD19^+ B cells	0.509	1.234(0.661–2.306)			0.002	2.278(1.340–3.873)	0.026	1.847(1.077–3.165)
NK cell	0.931	1.027(0.561–1.881)			0.458	0.842(0.534–1.326)
Treatment	0.518	1.474(0.455–4.772)			0.158	0.242(0.034–1.739)

Notes: Sex (male/female), Age (≤46 years/>46 years), Smoking (Yes/No), Family history of NPC (Yes/No), Pathology (undifferentiated/differentiated), Tumour stage (T1+T2/T3+T4), Node stage (N0+N1/N2+N3), Clinical stage (I+II/III+Iva), NLR (≤2.18/>2.18), Albumin (≤44.7g/L/>44.7g/L), Hb (≤140g/L/>140g/L), LDH (≤170U/L/>170U/L), CD3⁺ T cells (≤64.9%/>64.9%), CD4⁺ T cells (≤37.05%/>37.05%), CD8⁺ T cells (≤23.1%/>64.9%), CD4/CD8 ratio (≤1.35/>1.35), CD19⁺ B cells (≤9.55%/>9.55%), NK cell (≤15%/>15%), Treatment (RT/RT+Chemotherapy).

Abbreviations: NPC, nasopharyngeal carcinoma; NLR, neutrophil-to-lymphocyte ratio; OS, overall survival; PFS, progression-free survival; LRFS, locoregional relapse-free survival; DMFS, distant metastasis-free survival; Hb, hemoglobin; LDH, lactate dehydrogenase; RT: radiotherapy.

Table 4 Effects of Chemoradiotherapy on Lymphocyte Subsets

Lymphocyte Subsets	Before Chemoradiotherapy (Median)	After Chemoradiotherapy (Median)	P-value
CD3^+ T cells (%)	63.35	64.15	0.536
CD4^+ T cells (%)	32.60	21.35	0.000
CD8^+ T cells (%)	23.05	29.6	0.000
CD4/CD8 ratio	1.40	0.70	0.000
CD19^+ B cells (%)	8.75	3.1	0.000
NK cell (%)	15.65	16.75	0.007