Table 1 Immune regulatory metabolites and noncoding RNAs
From: Noncoding RNAs link metabolic reprogramming to immune microenvironment in cancers
Metabolites | References (PMID) | Role in antitumor immunity | Reported function in immune microenvironment | Noncoding RNAs participated in generation or utilization of the metabolite | References (PMID) |
|---|---|---|---|---|---|
Acetate | 31091446 | Friend | Acetate promotes T cell effector function during glucose restriction | IFNG-AS1; miR-146a | 33434756 |
Adenosine | 29059149; 29229600 | Foe | Activate antitumor immune responses and suppress natural killer cell maturation in the tumor microenvironment | NA | NA |
Arginine | 23017138; 27745970 | Friend | Maintain T cell proliferation and proper function | miR-1291 | 33051382 |
Branched-chain amino acid | 29141216; 27422517 | Friend | Nanoliposome C6-ceramide increases the antitumor immune response and slows growth of liver tumors in mice | NA | NA |
Ceramide | 29408569 | Friend | Nanoliposome C6-ceramide increases the antitumor immune response and slows growth of liver tumors in mice | miR-34a; miR-29b | 32056304; 32746845 |
Cholesterol | 32694690 | Foe | Cholesterol-derived metabolites play complex roles in supporting cancer progression and suppressing immune responses | MeXis; MEG3; miR-128-1; miR-148a; miR-130b; miR-301b | 29431742; 27770549; 26501192 |
Citrate | 31751601 | Friend | Citrate can impact the behaviors of both cancer and immune cells, resulting in induction of cancer cell apoptosis, boosting immune responses and enhanced cancer immunotherapy | NA | NA |
Creatine | 31628186 | Friend | Creatine as an important metabolic regulator controlling antitumor T cell immunity, underscoring the potential of creatine supplementation to improve T cell-based cancer immunotherapies | NA | NA |
Cysteine | 20070126 | Friend | Cysteine has a positive signaling effect (induction) on T cells proliferation and activation | LINC00618; miR-375; miR-139-5p | 33002417; 28627030; 32109492 |
Lipid peroxidation byproducts | 26073941; 33627871 | Foe | Reverse the antitumor function by dendritic cells | NEAT1; circACC1; MACC1-AS1; LNMICC | 29764424; 31155494; 30742067; 29229603 |
Glucose | 23746840 | Friend | Glucose-glycolysis-posttranslational modification of IFN-y mRNA-T cell effector function | miR-101 and miR-26a | 26523864 |
Glutamate | 25351939 | Foe | Glutamate in turn has a direct inhibitory effect to T cell proliferation and activation | XLOC_006390; HOXA; Glu; CCAT2 | 31734356; 29844833; 32030797; 28934601 |
Glutamine | 22885179 | Friend | Maintaining optimal glutamine levels is critical in preventing the MDSC-mediated immunosuppression | LincRNA-p21; miR-137; miR-133a-3p; circHMGCS1; circHECTD1; GLS-AS; OIP5-AS1; lincRNA-p21; EPB41L4A-AS1; HOTAIR; UCA1; HOTTIP; TUG1; miR-122; miR-140-5p; miR-203; miR-23a/b; miR-513c; miR-153; miR-105; miR-9; miR-450a; miR-145; miR-103a-3p | 30902882; 29348676; 30572959; 30809316; 31371702; 30563888; 30779126; 30902882; 30796006; 28597996; 22634383; 28800318; 28218035; 29662176; 29319172; 26373319; 26710269; 29371936; 32180557; 31986891; 30572959; 30035324; 31101765; 31115975; 31606381 |
Hyaluronic acid oligomers | 30930171 | Foe | Cancer cells secrete hyaluronic acid oligomers, thereby increasing cholesterol efflux in TAMs and directing TAMs toward an M2-like phenotype that accelerates tumor progression | NA | NA |
Itaconic acid | 29920191 | Foe | Tumor-macrophagy-itaconic acid-tumor growth | miR93 | 28356443 |
Kynurenine | 31068703; 29533786 | Foe | The metabolite of Tryptophan that inhibits T effector activation and increases PD-1 expression | miR-153; ITGB2-AS1; HCP5; miR155HG; miR-30b | 32165090; 29685162; 31093946 |
Lactate | 31155231 | Foe | Lactate is responsible for glycolysis-mediated RLR signaling inhibition to shrink from cancer immune surveillance | GLCC1; MALAT1; HULC; circDENND4C; miR-30a-5p; miR-21; Ftx; HOTAIR | 31375671; 31953613; 32572027; 31488193; 28461244; 30664688; 29845188; 32062551 |
Microbiota/food-derived short-chain fatty acids | 31272808 | Friend | Microbiota-derived short-chain fatty acids promote the memory potential of antigen-activated CD8(+) T Cells | miR-106b; miR-125a; miR-30c; miR-182; miR-200c; let-7a | 21283757; 31896754 |
Polyunsaturated fatty acids | 30073695 | Friend | Decrease cancer progression with an antitumor immune response | miR-138-5p | 31783879 |
Prostaglandin E2 | 22187483 | Foe | Enhance local accumulation of regulatory T cells and myeloid-derived suppressor cells and suppresses DC's ability to attract naive, memory and effector T cells | miR675-5p; miRNA-206; miR-21; miR-708-5p | 31734182; 30135139; 29687845; 32655834 |
Pyrimidine | 30827862 | Foe | Macrophagy-pyrimidine-tumor-drug sensitivity | miRNA-375-3p | 32073706 |
R-2-hydroxyglutarate | 29988124 | Foe | Tumor cell-derived R-2-HG is taken up by T cells where it induces a perturbation of nuclear factor of activated T cells transcriptional activity and polyamine biosynthesis, resulting in suppression of T cell activity | circRNA-51217 | 31846689 |
Retinoic acid | 32169218 | Foe | Tumor-derived retinoic acid regulates intratumoral monocyte differentiation to promote immune suppression | miR-124-3p; miR-302b; miR-29b; miR-664a-5p; miR-10a/b;miR-21 | 25753094; 25040912; 29619741; 29341475; 21131358; 21212796; 25934412; 21131358 |
S-2-hydroxyglutarate | 27798602 | Friend | S-2-hydroxyglutarate treatment greatly enhances the in vivo proliferation, persistence and antitumor capacity of adoptively transferred CD8+ T cells | NA | NA |
Sarcosine | 31753028 | Friend | Sarcosine promotes trafficking of dendritic cells and improves efficacy of antitumor dendritic cell vaccines via CXC chemokine family signaling | NA | NA |
Saturated fatty acids | 31620124 | Foe | Impair antigen presentation and NKT function by reducing the CD1d expression on surface | NA | NA |
Succinate | 33023985 | Foe | Breast cancer-associated macrophages promote tumorigenesis by suppressing succinate dehydrogenase in tumor cells | miRNA-4470 | 31304868 |
Taurine | 29945116 | Friend | Alter splenocytes immunological profile of CD3+ CD4+ , CD3+ CD8+ , CD4+ CD25+ and CD11b+ Ly6G+ cells to achieve better immune surveillance against tumor cells | TUG1 | 30912122 |
Tetrahydrobiopterin (BH4) | 30405245 | Friend | Enhance antitumor immunity by promoting T cell activation and proliferation | miR-124; miR-206 | 31210282; 29436714 |
Triglycerides | 20622859 | Foe | Lipid accumulation and dendritic cell dysfunction in cancer | miR-132; HULC; NEAT1; miR-124-3p | 25592151; 28381526 |
Tryptophan | 23090118 | Friend | Activate T cells; The target that IDO-expressing cells used to inhibit T cell activation | miR-448; miR-153; circZNF566; miR-18a; miR-669b-3p | 31391111; 29685162; 32532962; 30268986; 32687860 |
Vitamin D | 26811638 | Friend | Vitamin D regulates immune cell trafficking and differentiation | CCAT2; MEG3; miR-155 | 32230936; 32219064; 30639520 |
22-hydroxycholesterol | 23897983 | Foe | Recruit neutrophils via oxysterol-CXCR2 axis | NA | NA |
25-hydroxycholesterol | 23541792 | Foe | Interacts with G-protein-coupled receptor 183 and triggers migration of both macrophages and human blood monocytes by reorganizing the cytoskeletal protein vimentin8 | miR-139-5p; miR-33a | 28257846; 32109243 |
1-pyrroline-5-carboxylate | 30545412 | Foe | Attenuate T cell-mediated antitumor immunity | NA | NA |
27-hydroxycholesterol | 29021522 | Foe | The pro-metastatic actions of 27-hydroxycholesterol requires both polymorphonuclear-neutrophils and γδ-T cells, and 27-hydroxycholesterol treatment results in a decreased number of cytotoxic CD8+ T lymphocytes | miR-933 | 29966198 |