. 2020 Sep 21;12(9):2692. doi: 10.3390/cancers12092692

Table 1.

Prognostic value of infiltrating CD8⁺ and CD3⁺ T cells.

Ref	N	Stage	UC only	Methods	Relation with Survival
Ref	N	Stage	UC only	Methods	Outcome Parameter	Immune Marker	HR ¹	95% CI	p	Adjusted for
[10]	115	Low-grade NMIBC	Yes	IHC	RFS	CD3	5.83 ²	1.52–22.36	0.010	Tumor size, T stage, GZMB and CD4,20,56,68
[10]	115	Low-grade NMIBC	Yes	IHC	RFS	CD8	5.33 ²	1.51–18.74	0.009	Tumor size, T stage, GZMB and CD4,20,56,68
[25]	302	NMIBC: 212 MIBC: 90	Yes	IHC	OS	CD8 ^INT	0.87	0.46–1.65	0.67	Age, T and N stages, tumor size and grade
[25]	302	NMIBC: 212 MIBC: 90	Yes	IHC	RFS	CD8 ^INT	0.68	0.46–1.01	0.057	-
[21]	69	NMIBC: 38 MIBC: 31	Yes	IHC	OS	CD8 ^INT	0.3	0.09–0.96	0.042	T stage
[21]	69	NMIBC: 38 MIBC: 31	Yes	IHC	DFS	CD8 ^INT	0.79	0.27–2.33	0.67	T stage
[8]	253	NMBIC: 201 MIBC: 52	Yes	IHC	PFS - NMIBC	CD3, CD8	NR	NR	ns	-
					CSS - MIBC	CD3	0.60	0.41–0.89	0.009
					CSS - MIBC	CD8	0.82	0.57–1.16	0.26
[18]	67	NMIBC: 5 MIBC: 62	No	IHC	OS	CD3 ^INT	2.91	0.85–10.0	0.09	Stage, LVI, surgical margins, prior BCG and (N)AC
						CD3 ^IM	0.57	0.12–2.63	0.47
						CD8 ^INT	0.32	0.09–1.11	0.07
						CD8 ^IM	0.33	0.12–0.88	0.03
					DFS	CD3 ^INT	1.27	0.46–3.53	0.64
						CD3 ^IM	0.60	0.16–2.17	0.43
						CD8 ^INT	0.55	0.18–1.65	0.29
						CD8 ^IM	0.35	0.14–0.86	0.02
[11]	102	NMIBC: 53 MIBC: 49	Yes	IHC	OS	CD8	0.66	0.28–1.58	0.35	T stage, tumor size, grade, NLR and neutrophils
[19]	60	T1	Yes	IHC	PFS	CD3 ^INT	NR	NR	0.69	-
[19]	60	T1	Yes	IHC	CSS	CD3 ^INT	NR ³	NR	0.045	-
[20]	37	NMIBC: 4 MIBC: 33	Yes	IHC	OS	CD3 ^INT/IM	0.42	0.18–1.00	0.049	Age, gender, T and M stages, and (N)AC
[20]	37	NMIBC: 4 MIBC: 33	Yes	IHC	PFS	CD3 ^INT/IM	0.09	0.02–0.48	0.004	Age, gender, T and M stages, and (N)AC
[22]	56	NMIBC: 11 MIBC: 45	Yes	IHC	OS	CD8 ^INT	0.1	0.01–0.69	0.02	T and N stages, and LVI
[22]	56	NMIBC: 11 MIBC: 45	Yes	IHC	CSS	CD8 ^INT	0.05	0.01–0.62	0.02	T and N stages, and LVI
[12]	404	MIBC ⁴	Yes	RNA-seq, TIMER	OS	CD8	7.70	1.60–36.97	0.12	Age, stage, B cells, DCs, neutrophils and TAMs
[24]	287	MIBC ⁴	Yes	RNA-seq, CIBERSORT	OS	CD8	0.15	0.014–1.75	0.13	-
	118	MIBC	No	IHC	OS	CD8 ^INT	0.91	0.84–0.98	0.016
	118	MIBC	No	IHC	OS	CD8 ^ST	0.97	0.94–0.99	0.003
	140	MIBC	No	IHC	OS	CD8 ^INT	0.94	0.90–0.99	0.015
	140	MIBC	No	IHC	OS	CD8 ^ST	0.98	0.97–0.99	0.001
[13]	407	MIBC ⁴	Yes	RNA-seq	OS	CD3D	NR ⁵	NR	0.032	Age, gender and T stage
[13]	407	MIBC ⁴	Yes	RNA-seq	OS	CD8A	NR ⁵	NR	0.06	Age, gender and T stage
[14]	248	NMIBC: 129 MIBC: 119	Yes	IHC	OS	CD8 ^ST	NR ⁶	NR	<0.01	-
[14]	248	NMIBC: 129 MIBC: 119	Yes	IHC	RFS	CD8 ^ST	NR	NR	0.99	-
[15]	149	NMIBC: 18 MIBC: 131	Yes	IHC	OS	CD3	0.84	0.68–1.04	0.11	-
					OS	CD8	0.80	0.63–1.02	0.07
					CSS	CD3	0.81	0.63-1.03	0.089
					CSS	CD8	0.75	0.56-1.01	0.56
[16]⁷	302	NMIBC: 212 MIBC: 90	Yes	IHC	OS	CD8 ^INT	0.43	NR	0.003	NR
[16]⁷	302	NMIBC: 212 MIBC: 90	Yes	IHC	OS	CD8 ^ST	2.21	NR	0.009	NR
[17]	44	NMIBC: 5 MIBC: 39	No	IHC	CSS	CD8	0.95	0.20–3.55	0.947	T and N stages, and CD169⁺ cells
[26]	67	T1	Yes	IHC	OS	CD8 ^INT	0.36	0.07–1.40	0.13	Tumor size and multifocality
[9]	221	NMIBC: 43 MIBC: 178	Yes	IHC	OS	Immunoscore	2.01 ¹	1.20–3.36	0.008	T and N stages, and vascular invasion

Abbreviations: GZMB = granzyme B; IHC = immunohistochemistry; IM = invasive margin, INT = intraepithelial, LVI = lymphovascular invasion, MIBC = muscle-invasive bladder cancer; (N)AC = (neo)adjuvant chemotherapy; NMIBC = nonmuscle invasive bladder cancer; NR: not reported, RFS = recurrence-free survival; RNA-seq = RNA sequencing; ST = stromal; UC: urothelial carcinoma. ¹ HR > 1 indicates increased risk of an event in patients with higher immune cell infiltration, except for the Immunoscore in the last row. ² OR instead of HR. OR >1 indicates increased risk of recurrence. ³ Positive association with CSS (100% vs. 70%). ⁴ Datasets partially overlap. ⁵ Positive association with OS. ⁶ Negative association with OS (median OS 48 vs. 59 months). ⁷ Only an abstract is available.