Table 1 The effects of metabolism on the immune microenvironment of colorectal cancer.
From: The effects of metabolism on the immune microenvironment in colorectal cancer
Metabolisms and metabolites | Biological effects to immune | Metabolites/enzymes involved | Roles of the metabolisms/enzymes | Results of related factors | Affected immune factors in TME | Effectiveness for CRC |
|---|---|---|---|---|---|---|
amino acid metabolism | ||||||
glutamine | substrating for the proliferation, activation and efficacy of immune cells | glutamine↑ | enhancing CRC cells survival and proliferation | Acetate-TCA↓ | CD8+T ↓(17, 18) | promoting immune escape in CRC |
Tryptophan | nutritionally essential amino acids | kyn↑ | enhancing the invasiveness of CRC cells | kyn-AHR-CXCL5↑ | M2 TAMs↑(27, 28) | helping CRC with immune evasion |
kyn-FOXP3↑ | Tregs↑(29,30) | helping CRC with immune evasion | ||||
TOX | CD8+T ↓(30,31) | reducing immune efficacy against CRC | ||||
|  |  | IDO↓ | of CRC cells | IDO-AHR | TH17/TH1↓(33) | promoting the development of CRC |
glucose metabolism | ||||||
glycolysis | energy transporter and energy supplier | PI3K↑ | markers of glycolytic disorders in CRC | STAT3/miR- 19a/PI3K(39) |  |  |
mTOR↑ | RAS-mTOR(40) |  |  | |||
HIF↑ | AKT-mTOR-HIF1α(41) |  |  | |||
G6PD↑ | assisting in the metabolism of glucose | HK2-IκBα phosphorylation | CD8+T ↓(45) | promoting immune escape in CRC | ||
Hyperglycemia | the feature of TME in CRC | MondoA-TXNIP | Tregs↑(49) | promoting the development of CRC | ||
|  |  | Akt/mTORC1-CRC cellular autophagy | T cells ↓(50) | promoting the development of CRC | ||
lactic acid | an important fuel in human metabolism and TCA cycle | LDHA↑ | improve lactate | TH1-INFγ↓ | CD8+T ↓(54) | helping with immune escape in CRC |
|  |  | G protein-coupled receptor-dependent expression of ICER | M2-TAMs↑(55) | promoting the development of CRC | ||
lipid metabolism | ||||||
fatty acid | anti-inflammatory and immunomodulatory roles | LDs↑ | main site of intracellular fat storage | ATGL/HSL-FAA↑ | M2-TAMs↑(63) | promoting the development of CRC |
|  |  | CRT↓ | DC↓(61) | promoting the development of CRC | ||
|  |  |  | CD8+T ↓(61) | helping with immune escape in CRC | ||
|  | Prostaglandins↑ | regulates the function of various | PGE2/EP1-Fas/FasL↓ CD8+T ↓(65,66) | helping with immune escape in CRC | ||
(PGE2) | immune cells by binding to downstream receptors to affect TME | PGE2/EP4↑ | M2-TAMs↑(67) | promoting the development of CRC | ||
CPT1A↑ | a key rate-limiting enzyme for fatty acid β-oxidation | FAO↑ | MDSCs↑-T cells ↓(69) | promoting the development of CRC | ||
|  |  |  | PD- 1 ↑IA↑-Teffs ↓-IFN-γ ↓(70) | promoting the development of CRC | ||
|  |  |  | CD206 macrophages↑(63) | Poor prognosis | ||
gut microbiome | important components involved in intestinal homeostasis | SCFAs | GPR43↑ | inhibiting the progression of CRC | ||
cholesterol | inducing immune cell initiation and activation | cholesterol↑ | immune cell initiation and activation | AMPKα↓ | ROS-NLRP3-CCL5-p65/STAT3-CSN5-PD-L1↑(77,78) | helping with immune escape in CRC |
|  |  | PD-L1↑2B4↑ | CD8+T ↓(79) | promoting immune escape in CRC | ||
DCA↑ | main production of cholesterol metabolism | PI3K/AKT-EGFR↑ | CD8+T ↓(80-82) | promoting immune escape in CRC | ||
|  |  | ERK1/2 ↑-p53↓ | immunological effects in TME↓(36,83) | promoting the development of CRC | ||
|  |  | β-linked proteins↑ | make proinflammatory Tregs(84) | promoting the development of CRC | ||
phospholipids | providing a permeability barrier and substrates for lipid-mediated synthesis | LPA↑ | phospholipid messenger | Agpat4/LPA↑-p38/p65↑-IL1β/IL-6 ↑ | M1 macrophage-dependent T-cells activation↑(86) | inhibiting the progression of CRC |
camptothesomes↑ | ICD inducers | CTLs-PD-L1/PD- 1 ↑ | CD8+T ↑(87) | inhibiting the progression of CRC | ||
