Comprehensive Analyses of the Infiltrating Immune Cell Landscape and Its Clinical Significance in Hepatocellular Carcinoma

Figures & data

Figure 1 Comparisons of adaptive immune cells between HCC and normal tissues. Median with 95% confidence interval were shown as red lines. (A) naive B cells; (B) memory B cells; (C) plasma cells; (D) total B cells; (E) CD8+ T cells; (F) naive CD4+ T cells; (G) resting CD4+ memory T cells; (H) activated CD4+ memory T cells; (I) follicular helper T cells; (J) regulatory T cells; (K) gamma delta T cells; (L) total T cells. *P<0.05; **P<0.001.

Figure 2 Comparisons of innate immune cells between HCC and normal tissues. Median with 95% confidence interval were shown as red lines. (A) resting NK cells; (B) activated NK cells; (C) monocytes; (D) M0 macrophages; (E) M1 macrophages; (F) M2 macrophages; (G) resting dendritic cells; (H) activated dendritic cells; (I) resting mast cells; (J) activated mast cells; (K) eosinophils; (L) neutrophils. *P<0.05; **P<0.001.

Table 1 Fraction of Immune Cells

Immune Cell Type	Normal (n=50)	HCC (n=374)	P-value
Naive B cells	0.0336±0.0209	0.0368±0.0360	0.360*
Memory B cells	0.0008±0.0049	0.0005±0.0037	0.724
Plasma cells	0.0291±0.0260	0.0199±0.0344	0.071
CD8+ T cells	0.0885±0.0502	0.0999±0.0956	0.192*
Naive CD4+ T cells	0.0000±0.0000	0.0009±0.0061	0.295
Resting CD4+ memory T cells	0.1392±0.0605	0.1701±0.1130	0.004*
Activated CD4+ memory T cells	0.0005±0.0017	0.0060±0.0180	<0.001*
Follicular helper T cells	0.0087±0.0108	0.0145±0.0215	0.003*
Regulatory T cells	0.0166±0.0207	0.0509±0.0399	<0.001*
Gamma delta T cells	0.0462±0.0347	0.0140±0.0243	<0.001*
Resting NK cells	0.0065±0.0144	0.0082±0.0227	0.590
Activated NK cells	0.0509±0.029	0.0550±0.0351	0.431
Monocytes	0.0722±0.0609	0.0232±0.0321	<0.001*
M0 macrophages	0.0356±0.0470	0.1240±0.1128	<0.001*
M1 macrophages	0.0914±0.0536	0.0830±0.0424	0.296*
M2 macrophages	0.2995±0.0982	0.1837±0.0876	<0.001
Resting dendritic cells	0.0112±0.0181	0.0302±0.0429	<0.001*
Activated dendritic cells	0.0003±0.0018	0.0011±0.0092	0.552
Resting mast cells	0.0425±0.0424	0.0708±0.0635	<0.001*
Activated mast cells	0.0118±0.0243	0.0015±0.0104	0.005*
Eosinophils	0.0002±0.0012	0.0005±0.0027	0.399
Neutrophils	0.0149±0.0232	0.0051±0.0147	0.005*

Notes: (%) Mean±SD; *using Welch’s ANOVA.

Figure 3 (A) A bar plot of the fractions of 22 types of immune cells in HCC and normal control tissues; (B) a heatmap of 22 types of immune cells in HCC and normal control tissues; (C) a correlation heatmap of 22 types of immune cells in HCC tissues.

Table 2 Patient Baseline and Tumor Characteristics

Variable	Number of Patients	%
Age
<60	172	45.6
≥60	204	54.1
Missing	1	0.3
Gender
Female	122	32.4
Male	255	67.6
Histologic Grade
G1	55	14.6
G2	180	47.7
G3	124	32.9
G4	13	3.5
Missing	5	1.3
AJCC Stage
Stage I	175	46.4
Stage II	87	23.1
Stage III	86	22.8
Stage IV	5	1.3
Missing	24	6.4

Figure 4 Kaplan-Meier curves of follicular helper T cells (A), monocytes (B), M0 (C) and M2 macrophages (D) for overall survival in HCC patients.

Figure 5 Differences of the fraction of follicular helper T cells, monocytes, M0 and M2 macrophages in each histological grade (A–D) and clinical stage (E–H) of HCC.

Figure 6 Comparisons of monocytes (A) and M2 macrophages (B) between HCC and normal tissues using xCell. Median with 95% confidence interval were shown as red lines. **P<0.001.