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

Table 2.

Prognostic value of macrophages in BC.

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
[8]	253	NMBIC: 201 MIBC: 52	Yes	IHC	PFS-NMIBC	CD68	1.52	1.08–2.14	0.016	-
					PFS-NMIBC	CD163	NR	NR	NS
					CSS-MIBC	CD68	3.88	1.00–15.08	0.051
						CD163	0.99	0.69–1.41	0.95
						CD68/CD3 > 1	7.73	3.13–19.10	9.5 × 10^-6	T stage
[42]	94	T1, high grade	Yes	IHC	RFS	CD163	2.11	1.04–4.28	0.038	Gender, age, tumor size, multifocality, CIS, bladder instillations
					PFS	CD163	6.69	1.99–22.50	0.002
					CSS	CD163	5.86	1.41–24.30	0.015
[40]	302	NMIBC: 212 MIBC: 90	Yes	IHC	RFS	CD68 ^INT/ST CD204 ^INT/ST CD169 ^INT/ST	NR	NR	NS	-
					OS	CD68 ^INT	1.38	1.88–2.18	0.162	-
						CD68 ^ST	0.91	0.53–1.57	0.735	Age, tumor size, T and N stages, grade
						CD204 ^INT	1.04	0.59–1.84	0.887
						CD204 ^ST	1.981	1.10–3.56	0.022
						CD169 ^INT	1.51	0.91–2.52	0.11
						CD169 ^ST	1.60	0.94–2.73	0.08
[17]	44	NMIBC: 5 MIBC: 39	No	IHC	DSS	CD169	0.13	0.01–0.76	0.021	T and N stages, CD8⁺ T cells
[12]	404	MIBC	Yes	RNA-seq, TIMER	OS	TAMs	17.35	5.86–51.33	0.009	Age, stage, CD4⁺ and CD8⁺ T cells, neutrophils, TAMs and DCs
[24]	405	MIBC	Yes	RNA-seq ⁶, CIBERSORT	OS	TAMs	16.57	4.98–55.17	<0.000	-
						M1 TAMs	0.72	0.04–13.68	0.83
						M2 TAMs	0.94	0.16–5.65	0.95
	118	MIBC	No	IHC	OS	CD68 ^INT	1.03	1.01–1.05	0.005
	118	MIBC	No	IHC	OS	CD68 ^ST	1.02	1.01–1.02	<0.000
	140	MIBC	No	IHC	OS	CD68 ^INT	1.04	1.02–1.05	<0.000
	140	MIBC	No	IHC	OS	CD68 ^ST	1.01	1.01–1.02	<0.000
[10]	115	Low-grade NMIBC	Yes	IHC	RFS	CD68	3.88 ²	1.00–15.08	0.051	Tumor size, stage, GZMB and CD3,4,8,20,56
[43]	141	MIBC	No	IHC	OS	CD68	1.23	0.76–1.99	0.40	T stage, grade, LVI and AC
[43]	141	MIBC	No	IHC	RFS	CD68	1.40	0.78–2.52	0.26	T stage, grade, LVI and AC
[30]	93	Ta: 69 T1: 24	No	IHC	RFS	CD68	1.19	0.56–2.54	0.65	Gender, smoking status, age, stage, grade and multifocality
[44]	134	NMIBC: 19 MIBC: 115	Yes	IHC	OS	CD163	NR ³	NR	0.074	-
[44]	134	NMIBC: 19 MIBC: 115	Yes	IHC	PFS	CD163	NR ³	NR	0.090	-
[45]	184	NMIBC: 81 MIBC: 11	Yes	IHC	OS	CD68	1.01	0.99–1.01	0.19	Grade, T stage, age and multifocality

Abbreviations: CSS = cancer-specific survival; Gal-9 = Galectin-9; GZMB = granzyme B; IHC = immunohistochemistry; IM = invasive margin; INT = intraepithelial; MFS = metastasis-free survival; MIBC = muscle-invasive bladder cancer; NMIBC = nonmuscle invasive bladder cancer; OS = overall survival; PFS = progression-free survival; RFS = recurrence-free survival; RNA-seq = RNA sequencing; ST = stromal; TAMs = tumor-associated macrophages; UC: urothelial carcinoma. ¹ HR greater than 1 indicates increased risk of recurrence or death in patients with higher immune cell infiltration. ² OR instead of HR. OR >1 indicates increased risk of recurrence. ³ 3. Five-year OS 22% vs. 35.3% in patients with high vs. low CD163⁺ infiltration; Five-year PFS 23.7% vs. 32.2%.