Evaluating tumor-infiltrating lymphocytes in hepatocellular carcinoma using hematoxylin and eosin-stained tumor sections

Table 1 Clinicopathological data of the patients

Variable		No. of case
Age (median)		56 (204)
Gender	Male	174
	Female	30
HBV infection	Yes	187
	No	12
	Not mentioned	5
HBV DNA	Positive	66
	Negative	108
	Not mentioned	30
MaVI	Yes	21
	No	183
MVI	Positive	110
	Negative	94
Differentiation	Moderately differentiated	73
	Poorly differentiated	131
Histological subtype	Microtrabecular/pseudoglandular	87
	Macrotrabecular	108
	compact	5
	Lymphoepithelioma-like	4
Tumor number	Single	156
	Multiple (≥ 2)	48
Largest tumor diameter	≤ 10 cm	189
	> 10 cm	15
Capsule	Yes	117
	No	87
Cirrhosis in peritumor	Yes	171
	No	33
TILsCT	≤ 30	35
	> 30	169
TILsIF	≤ 200	62
	> 200	140
PILs	≤ 200	113
	> 200	89

MaVI: Macrovascular invasion; MVI: Microvascular invasion; TILs^CT: Tumor infiltrating lymphocytes in the tumor center; TILs^IF: Tumor infiltrating lymphocytes in the invasive front 1 mm spacing from the malignant nests, two cases cannot assess infiltrating lymphocytes in the invasive front; PILs: Infiltrating lymphocytes in the peritumor, two cases cannot assess infiltrating lymphocytes in peritumor areas; HBV: Hepatitis B virus.

Table 2 Results of univariate and multivariate analysis

Variable	Univariate analysis			Multivariate analysis
	HR	95% CI	P value	HR	95% CI	P value
MaVI	3.09	1.02-9.34	0.001	3.77	1.63-7.40	0.009
MVI	2.80	1.51-5.16	0.012	1.19	0.64-2.23	0.693
Tumor number	2.38	1.10-5.14	0.008	1.95	1.04-3.77	0.122
Largest tumor diameter	3.31	1.06-10.32	0.001	1.76	0.95-3.45	0.322
Capsule	1.99	1.07-3.70	0.026	0.42	0.20-0.83	0.031
Macrotrabecular histological subtype	3.22	1.77-5.86	0.001	1.89	1.03-3.67	0.104
TILsCT (≤ 30)	0.49	0.22-0.92	0.039	0.85	0.41-1.63	0.734
TILsIF (≤ 200)	0.37	0.14-0.98	0.014	0.46	0.25-0.86	0.047
PILs (≤ 200)	0.40	0.22-0.75	0.010	0.37	0.19-0.77	0.0495

MaVI: Macrovascular invasion; MVI: Microvascular invasion; TILs^CT: Tumor infiltrating lymphocytes in the tumor center; TILs^IF: Tumor infiltrating lymphocytes in the invasive front 1 mm spacing from the malignant nests; PILs: Infiltrating lymphocytes in the peritumor; HR: Hazard ratio; CI: Confidence interval.

Table 3 Clinicopathological data between the three immune subtypes

Variable		Immunehigh	Immunemod	Immunelow
HBV DNA	Positive	30	30	5
	Negative	38	54	16
	Not mentioned	15	10	6
MaVI	Yes	8	10	3
	No	75	84	24
MVI	Yes	34	58	18
	No	49	36	9
Tumor number	Single	60	78	18
	Multiple (≥ 2)	23	16	9
Largest tumor diameter	≤ 10	80	85	24
	> 10	3	9	3
Capsule	Yes	48	53	16
	No	35	41	11
Neutrophils	Yes	19	19	1
	No	64	75	26
Tertiary lymphoid structures	Yes	7	3	0
	No	76	91	27
Differentiation	Moderately differentiated	40	50	17
	Poorly differentiated	43	44	10
Histological subtype	Microtrabecular/pseudoglandular	39	40	13
	Macrotrabecular	38	52	14
	Compact	3	2	0
	Lymphoepithelioma-like	3	0	0
PD-L1 expression	Tumor cells	24	44	12
	TILs	79	94	26
Recurrence	Yes	9	24	9
	No	74	70	18

MaVI: Macrovascular invasion; MVI: Microvascular invasion; PD-L1: Programmed cell death-ligand 1; TIL: Tumor infiltrating lymphocyte; HBV: Hepatitis B virus.