Table 1 Cell populations contributing to the development of a favorable tumor microenvironment

Pro-tumor DCs

Bladder, Breast, Colon, Colorectal, Esophageal, Gastric, Glioma, Intestinal, Liver, Lung, Lymphomas, Osteosarcoma, Ovarian, Pancreas, Prostate

Enhanced production of pro-tumorigenic cytokine IL-6

Augmented secretion of immunosuppressive Galectin-1

Tumor-infiltrating DCs show an immune-tolerant phenotype favoring tumor growth

[4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21]

Immunosuppressive MDSCs

Bladder, Breast, Colorectal, Head and Neck, Liver, Lung, Pancreas, Prostate, Renal

Expression of immunosuppressive factors S100A8, S100A9 and Arg1

MDSCs promote immune suppression favoring tumor growth and metastasis

[16, 22,23,24,25,26,27,28,29,30,31]

TAMs

Bladder, Breast, Colon, Cervical, Gastric, Glioma, Lung, Lymphoma, Melanoma, Neuroblastoma, Ovarian, Pancreas, Prostate

Increased expression of Arg1

Activation of ALOX15

Enhanced expression of PPARγ

Decreased NFkB signaling and suppression of IL-1β expression

Immunosuppressive subsets of TAMs promote tumor growth

[16, 32,33,34,35,36,37,38,39,40,41,42]

TILs

Bladder, Brain, Breast, Colorectal, Gastric, Genitourinary, Glioblastoma, Glioma, Head and Neck, Liver, Lung, Melanoma, Meningioma, Ovarian, Pancreatic, Prostate, Renal

Impaired TILs CD8 + infiltration

Downregulation of CXCL9 and CXCL10 chemokine expression

Elevated levels of PD-1

Exhausted CD8 + T cells

Enhanced expression of CTLA4, PDCD1 and LAG3

Impaired CD8 + T cell functions as well as T-cell exhaustion seem to play a major role in the generation of an immunosuppressive TME

[43,44,45,46]

Mature Tregs

Bladder, Breast, Colorectal, Glioblastoma, Lung, Lymphoma, Melanoma, Ovarian, Pancreas

Downregulation of genes involved in effector T-cell activation

Mature Tregs provide a tumor-supportive microenvironment

[16, 47,48,49,50]

NK cells

Breast, Colorectal, Gastric, Melanoma, Multiple myeloma, Pancreas, Renal

Decreased expression of activating NKG2D NK-cell receptor

Impaired NK-cell mediated anti-tumor immune response

[51,52,53,54]

Fibroblasts

Fibroblasts in the TME differentiate into cancer-associated fibroblasts (CAFs), representing one of the main components in the tumor stroma. The majority of the studies show pro-tumoral functions for CAFs, which include immune suppression, extracellular remodeling and angiogenesis

[55,56,57]

Endothelial cells

Angiogenesis refers to the de novo formation of blood vessels, a process essential for tumor growth. This blood vasculature consists of tumor endothelial cells (TECs), which line the insides of the blood vessels. Different characteristics between TECs and normal endothelium have been described

[58, 59]

Blood and lymphatic vascular networks

Blood and lymphatic vascular networks play a key role in supporting tumor growth and progression. They support oxygen supply and adequate nourishment to the tumor and provide a gateway for metastasizing tumor cells

[60]

Extracellular matrix

The tumor extracellular matrix (ECM) differs greatly from the ECM in normal tissue, not only in amount of deposition but also in organization and composition. The tumor ECM is generally stiffer, a characteristic that has been associated with an increase in nuclear localization of transcription factors able to drive epithelial-mesenchymal-transition and, consequently, tumor metastasis

[61]