Table 1.

Overview of studies investigating tumor-infiltrating (TIDCs) and circulating dendritic cells (DCs) in colorectal cancer (CRC) patients.

CRC (n)	Experimental setup	DC characterization	Key conclusions	Reference
TIDCs – interactions with other immune cells and correlations with disease progression and prognosis
121	Tissue IHC	S100	↑ S100+ DCs ↔ good prognosis, higher survival, often without metastasis and ↑ lymphocyte infiltration	(Ambe, Mori, & Enjoji, 1989) (149)
30	Tissue IHC	S100	↑ S100+ DCs ↔ good prognosis ↓ S100 +DCs ↔ lymph node and hepatic metastasis, >stage III	(Nakayama et al., 2003) (150)
104	Tissue IHC	S100 and HLA-II	↑ S100+ DCs ↔ ↑ T cell infiltration and disease-free survival	(Dadabayev et al., 2004) (151)
40	Tissue IHC	S100, CD11c, CD208, CD209, CD123, and CD1a	S100+ DCs ↔ Tregs ↑ S100+ DCs ↔ prolonged survival ↓ S100+ DCs ↔ worse prognosis	(Nagorsen et al., 2007) (152)
16	Tissue IHC	CD205	↓ CD205+ DCs and high HMGB1 expression by CRC ↔ lymph node metastasis	(Kusume et al., 2009) (153)
52	Tissue IHC	CD11c+	↓ CD11c+ myeloid DCs ↑ Tregs ↔ tumor invasion, advanced stage, lymph node metastasis and poor prognosis	(Gai, Li, Song, Lei, & Yang, 2013) (154)
63	Tissue IHC	CD123 (pDCs)	↑ pDC/myeloid DC ratio and ↑ Tregs ↔ lymph node metastasis	(Gai, Song, Li, Lei, & Yang, 2013) (155)
149	Tissue IHC	BDCA-2+ (pDCs)	↑ pDC ↔ TLS and prolonged survival	(Kießler et al., 2021) (156)
58	Flow cytometry and RNA sequencing	BDCA-2+ (pDCs)	↑ pDC ↓innate lymphoid cells ↔ advanced disease stage	(Wu et al., 2021) (157)
TIDCs – maturation status and distribution
57	Tissue IHC	CD83, HLA-DR, CD40, and CD86	Density of mDCs: Normal mucosa > primary CRC > metastatic CRC No association with TGF-β or IL-10	(Schwaab, Weiss, Schned, & Barth, 2001) (158)
17	Tissue IHC	CD83 and CD1a	CD83+ mDCs: present in the invasive margin and cluster with T cells CD1a+ iDCs: scattered in the tumor stroma	(Suzuki et al., 2002) (159)
60	Tissue IHC	CD1a, S100, CD83, and HLA-DR	CD83+ mDCs: present around metastases and in the sinusoidal lumen CD1a+ iDCs: scattered in the tumor stroma	(M. Gulubova, Manolova, Cirovski, & Sivrev, 2008) (160)
26	Tissue IHC and gene expression	CD83	Primary site and lymph nodes: ↓ CD83+ mDCs ↔ high COX2 and IL-6	(Cui et al., 2007) (161)
23	Tissue IHC and gene expression	CD1a, CD83, and CD208	↓ CD83+ CD208+ mDCs ↑ CD1a+ iDCs ↔ increasing COX2 expression	(Yuan et al., 2008) (162)
69	Tissue IHC	S100, CD208	In MSI tumors in comparison with MSS: ↑ CD208+ mDCs and ↓ Tregs	(Bauer et al., 2011) (163)
133	Tissue Gene expression	Genes implicated in immune response	In MSI tumors in comparison with MSS: ↑ co-stimulatory molecules in DCs	(Banerjea et al., 2004) (164)
TIDCs – maturation status and correlations with disease progression and prognosis
70	Tissue IHC	CD83	↓ CD83+ mDCs ↔ poor prognosis	(Miyagawa et al., 2004) (165)
22	Tissue IHC	CD83	↓ CD83+ mDCs ↔ advanced disease and lymph node metastasis ↑ CD83+ mDCs and IL-12 expression ↔ better prognosis	(Inoeu et al., 2005) (166)
142	Tissue IHC	HLA-DR, CD1a, and CD83	↓ CD83+ mDCs ↔ shorter survival ↔ TGF-β expression by CRC	(Maya Gulubova et al., 2010) (56)
86	Tissue IHC	HLA-DR, CD1a, and CD83	Metastasis in comparison to metastasis-free samples: ↓ CD83+ mDCs and ↑TGF-β	(Maya Gulubova et al., 2013) (167)
44	Tissue IHC	CD1a and DC-LAMP	↓TILs ↑ CD1a+ iDCs/DC-LAMP+ mDCs ratio and KRAS mutation ↔ higher risk of disease recurrence	(Kocián et al., 2011) (168)
145	Tissue IHC	CD1a, S100, CD83, and HLA-DR	↓ CD83+ HLA-DR+ mDCs in invasive margin ↔ advanced stage (metastasis) and worse prognosis	(Maya V. Gulubova et al., 2012) (169)
556	Gene expression	Several DC-related genes	↑ mDCs ↑ T cells ↔ low risk group	(M. Li et al., 2020) (170)
473	Gene expression	CD80, CD83, and CD86	↑ CD80+, CD83+, CD86+ mDCs ↔ CXCL8 expression by CRC	(E. Li et al., 2021) (171)
326	Gene expression	Several DC-related genes	↑ DCs, IL-12 and in TLS ↔ strong Th1 and CTL response and more favorable prognostic	(Coppola et al., 2011) (19)
104	Tissue IHC	S100, CD1a, CD208, and HLA- II	↑CD208+ mDCs in the stroma ↔ shorter overall survival ↑CD1a+ iDCs in the advancing margin ↔ shorter disease-free survival	(Sandel et al., 2005) (172)
71	Tissue IHC	CD83	↑ mDCs ↔ tumor invasion and lymph node metastasis	(Pryczynicz et al., 2016) (173)
221	Tissue IHC	CD11c and PD-L1	↑ CD11c+ PD-L1+ DCs ↔ good survival and ↑ CD8+ T cell density	(Miller et al., 2021) (174)
Blood circulating DCs - Numerical defects
106	Flow cytometry	HLA-DR and CD86	↓ Circulating DC ↔ ↑ TGF-β levels	(Huang et al., 2003) (175)
54	Flow cytometry	HLA-DR, CD11c, CD83, and CD86	Numerical and functional impairment of DC progenitors ↔ stage of the disease and ↑ VEGF levels	(Della Porta et al., 2005) (176)
27	Flow cytometry	BDCA-1, BDCA-2, BDCA-3, CD80, CD86, and HLA-DR	DCs number: healthy > metastatic > non-metastatic > chemotherapy treated subjects	(Bellik et al., 2006) (177)
26	Flow cytometry	CD33 and CD123	↓ CD123+ pDCs ↔ advanced stage	(Orsini et al., 2014) (178)
Blood circulating DCs - Functional defects
31	Flow cytometry, functional assays	CD11c, CD123 HLA-DR, CD80, CD86, and CD83	↑ immature myeloid cell progenitors Defective DC maturation ex vivo ↔ ↑ VEGF Anti-VEGF antibody treatment: ↑ ex vivo stimulatory capacity of DC ↔ ↑ antigen-specific allogenic T cell proliferation	(Osada et al., 2008) (179)
23	Flow cytometry, functional assays	CD40, CD80, and CD83	Defective generation of mature and functional DC ex vivo ↔ advanced disease stage ↓ Ability to present antigens to allogeneic T cells ↑IL-10 ↓IL-12 and TNF-α	(Orsini et al., 2013) (180)
16	Flow cytometry, functional assays	CD83 CD1a HLA-DR CD86 FITC, CD80, CD209, and CD206	Defective DC maturation ex vivo	(Maciejewski et al., 2013) (181)
30	Flow cytometry, functional assays	CD80, CD11c, HLA-ABC, HLA-DR, CD14, CD133, CD11b, CD209, and CD86	Defective DC maturation ex vivo ↓IL-12	(Hsu et al., 2018) (182)

↔: correlation/association, ↑ higher infiltration/higher density/increase, ↓ lower infiltration/lower density/decrease. IHC, immunohistochemistry; mDCs, mature DCs; iDCs, immature DCs.