Table 1.
Cellular interaction within the primary tumor and metastases environment.
| Cell type | Primary tumor | Metastasis | Effects on cancer cells |
|---|---|---|---|
| Fibroblasts | Provide lactate by undergoing RWE (65) Induce expression of FA transporter in breast cancer (66) | Provide increased glucose availability by decreasing their own glucose utilization (34) | PRO-TUMOR |
| Adipocytes | Induce CD36 expression in ovarian cancer (67) and FATP1 in melanoma (68) | Undergo lipolysis to fuel β-oxidation in omentum metastasis (61, 69) | |
| Tregs | Survival favored in high lactate environment (70) | Inhibit anti-tumor immune cells | |
| M2 macrophages | M2 polarization favored by lactate (70) | Actively recruited in the metastatic and pre-metastatic niche (71, 72) | |
| MDSCs | Proliferation induced by lactate (70) | Major regulators of pre-metastatic niche formation (73) | |
| NK cells | Mediate cytotoxic killing of cancer cells, but infiltration and activation is inhibited by lactate (70) and adenosine in the tumor environment (47) | Impaired by upregulation of inhibitory receptors on cancer cells (44) | ANTI-TUMOR |
| T-cells | Mediate cytotoxic killing of cancer cells, but infiltration and activation is inhibited by depletion of glucose, tryptophan and arginine or accumulation of glutamate (47) and lactate in the tumor environment (70) | Reduced density (74) and downregulated HLA1 expression (45) |
FA refers to fatty acid, FATP1 refers to Fatty Acid Transport Protein 1, MDSC refers to myeloid-derived suppressor cell, NK refers to natural killer cell, RWE refers to reverse Warburg effect, Tregs refers to regulatory T-cells.