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strategies showed some protective effects on tumor growth [4,18,19] . However, these effects were suboptimal
in clinical trials when the antibody against DEC-205, which is expressed in different subsets of DCs in
[20]
human, was conjugated with the tumor antigen NY-ESO . Therefore, when contemplating DCs for in vivo
targeting for tumor vaccination, it is important to consider the differences of targeting DC receptors and
[1,5]
their function .

THE CDC1S AND THEIR ROLES AGAINST CANCERS
The “cross-presentation” by DCs of tumor antigens that are expressed in solid tumors is crucial for
+
generating effective CD8 cytotoxic T lymphocytes (CTLs) [1,21] . Accumulated experimental evidence
[1,5]
revealed that distinct subtypes of DCs show various capacities to prime and activate different T cells .
Mouse cDC1s were identified as the most efficient cells in cross-presenting cellular-associated antigens to
[27]
[26]
[28]
[29]
+
initiate CD8 T cells [22-25] . The following transcription factors ICSBP (Irf8) , Id2 , Batf3 , Nfil3 were
reported to control the development of cDC1s. Further epistasis analysis after single-cell RNA sequencing
revealed a genetic hierarchy. The Nfil3 induces a transition from common DC precursors to express
high levels of Id2 and low levels of Zeb2. Upon Id2 induction, Batf3 expression is increased and Zeb2 is
repressed. Meanwhile, Id2 extinguished E-protein activity at the +41-kb Irf8 enhancer, and the expressed
BATF3 acted at the +32-kb Irf8 enhancer to maintain Irf8 activation for the commitment of cDC1
clonogenic progenitors [30,31] . Currently, the homolog and functional equivalent of mouse cDC1s have been
identified as CD141 (BDCA3) XCR1 DCs in humans [14,32,33] . Both mouse and human cDC1s selectively
+
+
express the chemokine receptor XCR1 and C-type lectin endocytic receptor CLEC9A [4,14,34,35] .
The role of cDC1s in antitumor immunity was investigated in different animal models. In the Batf3-/-
mouse, the rejection of highly immunogenic syngeneic tumors was impaired . Using 2-photon intravital
[28]
imaging, the spatial organization of DCs and macrophages within the tumor and their dynamics with T
cells were analyzed. It was found that macrophage populations were preferentially marginating tightly on
tumoral lesions, DC populations were typically in separate collagen-rich zones distal to tumor lesions.
Stable T cell interactions were largely confined to tumor margins, where macrophage populations
[36]
dominated and DC numbers were little . Analyzing the different types of human tumors in TCGA data
revealed that patients with a high ratio of the CD103 /CD103 gene showed better survival compared
+
-
+
[37]
to those with a low ratio . In mouse melanoma models, it was found that CD103 DCs were the only
+
antigen-presenting cells to transport intact antigens to lymph nodes for priming tumor-specific CD8
+
T cells. When CD103 DC progenitors in the tumor were expanded and activated, the effects of anti-
[38]
checkpoint inhibitor were enhanced for anti-tumor responses .
In the context of cancer, there are many different cell populations. In addition to cDC1s, several myeloid
cell populations, including tumor-associated macrophages, are also able to acquire tumor material.
However, cDC1s have been demonstrated to be superior to other cells in stimulating T cell activation
and proliferation [36-38] . The stimulatory function of cDC1s in tumors is not restricted to T cells only. IL-12
production by these cells support IFN-γ production from NK cells for eradicating established tumor
cells [39,40] . More importantly, activated NK cells can generate the chemokines CCL5 and XCL1 to recruit
[25]
cDC1s into the tumor microenvironment and promote cancer immune control . In melanoma patients,
it was found that the abundance of cDC1s is associated with intra-tumor gene expression of the cytokine
FLT3LG, which is predominantly produced by NK cells in tumors. The numbers of cDC1 is correlated with
[41]
NK frequency and the patients’ response to anti-PD1 immunotherapy . It was found that cDC1s might
be the main source of CXCL9 and CXCL10, and these chemokines are able to recruit CXCR3 effector T
+
cells [24,40,42,43] . Therefore, the cDC1s in tumors and their interactions with NK and effector T cells establish
local anti-tumor immunity to control and eventually, eradicate established tumors [24,40] .