|
Immune cells
|
|
T lymphocytes
| | | | |
|
CD8+ T cell
|
TME & TIME
|
CD3+CD8+
|
Cytotoxicity
|
Anti-tumoral
|
|
Th1 cell
|
TME & TIME
|
CCR6+CXCR3+
|
Production of IL-2 and IFN-γ
|
CD8+ T cell supporting
|
Anti-tumoral
|
|
Th2 cell
|
TME & TIME
|
Production of IL-4, IL-5 and IL-13
|
B cell responses supporting
|
Pro-tumoral
|
|
Th17 cell
|
TME & TIME
|
Production of IL-17A, IL-17F, IL-21, IL-22
|
Angiogenesis, tumorigenesis, immune regulation
|
Ambiguous
|
|
Treg cell
|
TME & TIME
|
CD4+FOXP3+CD25+
|
Immune suppression
|
Pro-tumoral
|
|
B lymphocytes
|
TME & TIME
|
CD19+CD20+CD138+
|
Antibody production, antigen presentation, TLSs formation
|
Anti-tumoral
|
|
Innate lymphoid cell (ILCs)
| | | | |
|
ILC1s
| | | | |
|
NK cells
|
TME & TIME
|
Expression of T-bet; Eomes+ CD27−
|
Cytotoxic functions without prior sensitization
|
Anti-tumoral
|
|
Non-NK cells
|
TME & TIME
|
Expression of T-bet; Eomes− CD27+
|
Secretion of IFN-γ and TNF-α to induce tumor dependent anti-tumor immune responses
|
Ambiguous
|
|
ILC2s
|
TME & TIME
|
Expression of GATA3; secretion of type 2 cytokines
|
Secretion of IL-5, IL-13, IL-4 to inhibit anti-tumor immunity
|
Pro-tumoral
|
|
ILC3s
|
TME & TIME
|
Expression of RORγt
|
Heterogeneous cells secreting various cytokines and chemokines
|
Ambiguous
|
|
Tumor-associated macrophages
| |
HLA-DR+CD68+ CD11c−
| | |
|
M1
|
TME & TIME
|
CD86+ CD80+ iNOS+
|
Promoting anti-tumor TH1 and TH17 immune responses
|
Anti-tumoral
|
|
M2
|
TME & TIME
|
CD163+CD206+
|
Supporting angiogenesis, tumor progression, and metastasis; immune suppression
|
Pro-tumoral
|
|
MDSCs
|
TME & TIME
|
CD11b+HLA-DR−
|
Differentiating into TAMs, immune suppression
|
Pro-tumoral
|
|
Dendritic cells
|
TME & TIME
|
Siglec-H+CD317+
|
Binary immune regulatory function shaped by TME
|
Ambiguous
|
|
Neutrophils
| |
CD14+HLA-DR+CD206−CD86−
| | |
|
N1
|
TME & TIME
|
Supported by TGF-β and G-CSF
|
Immune respond initiation, antigen presenting
|
Anti-tumoral
|
|
N2
|
TME & TIME
|
Supported by IFN-γ and hepatocyte growth factor
|
Remodeling ECM, promoting angiogenesis and tumor growth
|
Pro-tumoral
|
|
Stromal cells
|
|
Cancer-associated fibroblasts
|
TME
|
Cellular markers: α-SMA, FAP-α, FSP-1/S100A4, PDGFRβ
|
Promoting tumor cell proliferation and invasion, angiogenesis; ECM remodeling; bidirectional immune regulation
|
Pro-tumoral
|
|
Endothelia cells
|
TME
|
Cellular markers: CD31; consisting of blood vessels
|
Angiogenesis, tumor metastasis
|
Pro-tumoral
|
|
Pericytes
|
TME
|
Cellular markers: Calponin, CD90, DLK, NG2, PDGF-A, SMA
|
Promote primary tumor growth, negative regulator of metastasis,
|
Pro-tumoral
|
|
Adipocytes
|
TME
|
Cellular markers: CD34
|
Secretion of hormones, metabolites, growth factors, enzymes and cytokines
|
Pro-tumoral
|
|
Mesenchymal stem cells
|
TME
|
Cellular markers: CD105, CD90, CD117, CD133
|
Forming the premetastatic niche; promoting tumor initiation and progression
|
Pro-tumoral
|
|
Vessels
|
|
Blood vessel
|
TME
|
Tubular structures formed by endothelial cells (cellular markers: CD31)
|
Promoting metastasis and angiogenesis,
|
Pro-tumoral
|
|
Lymph vessel
|
TME
|
Tubular structures formed by lymphatic endothelial cells (cellular markers: LYVE-1, Podoplanin, PROX1, VEGFR-3)
|
Foster tumor metastasis, physical link between lymph nodes and tumor
|
Pro-tumoral
|
|
Extracellular matrix
|
|
Collagen, fibronectin, elastin, laminin
|
TME
|
Complex noncellular three-dimensional macromolecular network
|
Physical scaffold for cell, tumor cell dissemination, depot for cytokines and growth factors
|
Pro-tumoral
|
|
Matrix metalloproteases, Cathepsins
|
TME
|
Enzymes secreted and activated by malignant cells in extracellular matrix
|
ECM remodeling, aiding metastasis, angiogenesis and inflammation
|
Pro-tumoral
|
|
Immune molecules
|
|
Cytokines
|
TME & TIME
|
Mainly secreted by immune cells; acting in a paracrine, autocrine or endocrine manner
|
Promoting leukocyte growth, survival and activation; promoting tumor immunogenicity, tumor cell proliferation, angiogenesis
|
Ambiguous, mainly anti-tumoral
|
|
Chemokines
|
TME & TIME
|
Regulation of cell movement and leukocyte attractants
|
Promoting tumor cell migration, invasion and metastasis; promoting immune cell migration, maturation
|
Ambiguous, mainly anti-tumoral
|
|
Extracellular nonspecific chemicals
|
|
Oxygen
|
TME
|
Aerobic cellular respiration
|
Favor immunosuppressive phenotypes
|
Ambiguous
|
|
Amino acids
|
TME
|
Components and substrates for various critical processes in cell metabolism and physiology
|
Supporting physiological processes of both tumor and immune cells, immune regulation
|
Ambiguous
|
|
Glucose
|
TME
|
Major source of energy for cells
|
TME dependent influence of energy metabolism in both immune and tumor cells
|
Ambiguous
|
|
Lactate
|
TME
|
Products of glycolysis
|
Inhibiting anti-tumor immunity, decrease the pH within the TME
|
Pro-tumoral
|
|
Carbon dioxide
|
TME
|
Products of oxidative phosphorylation
|
Causing tumor tissue acidosis
|
Ambiguous
|
|
Fatty acids
|
TME
|
Involvement in biological progression and cell structure
|
Heterogeneous consequences for different cells, leading to immunosuppressive effects
|
Ambiguous
|
|
Metal ions
|
TME
|
Involvement in biological progression
|
Regulating tumor and immune cells
|
Ambiguous
|
