Controlling TIME: How MNK Kinases Function to Shape Tumor Immunity
Abstract
:1. Introduction
1.1. MAPK-Interacting Serine/Threonine-Protein Kinases
1.1.1. Eukaryotic Initiation Factor 4E (eIF4E)
1.1.2. Heterogeneous Nuclear Ribonucleoprotein A1 (hnRNP A1)
1.1.3. Sprouty 1/2
1.2. Cellular Heterogeneity of Tumor Immune Microenvironment
1.2.1. Innate Immunity
Macrophages
Myeloid-Derived Suppressor Cells
Tumor-Associated Neutrophils
1.2.2. Adaptive Immunity
T Lymphocytes
Regulatory T Cells (Tregs)
B-cells
2. Regulation of Different Immune Compartments by MNK Kinases and Their Effectors
2.1. Innate Immunity
2.1.1. Macrophages
eIF4E
hnRNP A1
Spry1/2
2.1.2. MDSCs
eIF4E
hnRNP A1
2.1.3. Tumor-Associated Neutrophils
eIF4E
Spry1/2
2.2. Adaptive Immunity
2.2.1. eIF4E
2.2.2. hnRNP A1
2.2.3. Spry1/2
3. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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eIF4E | hnRNP A1 | Sprouty 2 | ||
---|---|---|---|---|
Innate immune cells | Macrophages | i) Promotes an M1, pro-inflammatory phenotype by regulating IRF8 [62,63] ii) Stimulates translation of pro-inflammatory cytokines TNFα, IL-6 [58] | i) Inhibits transcription and expression of OPN, which is required for M2 phenotype [64,67] ii) Increases stability of Gm-csf mRNAs [69,112] | i) Suppresses expression of M2-associated genes (Il10, Arg1, Chil3) [72] ii) Induces expression of M1-associated genes (Nos2, Il6) [72] |
Myeloid-derived suppressor cells (MDSCs) | i) May promote MDSC survival and immunosuppressive phenotype [75] | i) OPN can promote MDSC expansion via the STAT3 pathway [64,76] | ||
Neutrophils | i) Promotes neutrophil survival by upregulating anti-apoptotic proteins (MCL1, BCL2) [21,82] ii) Promotes neutrophil-driven metastasis [21,82] iii) Induces myeloid-neutrophil differentiation in response to G-CSF [82] | i) Sustains activation of Src family and downstream pathways ERK1/2 and Akt [83,84] | ||
Adaptive immune cells | T lymphocytes | i) Induces cap-dependent translation of RFLAT-1, which transcribes RANTES mRNAs [86,88] ii) Induces expression of GATA-3 for TH2 differentiation [88,89,90] iii) Inhibits expression of FOXP3 in CD4+ T-cells [90,91,113] iv) Facilitates B-cell differentiation by inducing CD4+ T-cell production of IL-4 [93] | i) Inhibits TNFα translation and expression by binding to TNFα 3′-UTR [4] | i) Inhibits expression of IL-2, IFNγ, and Granzyme B [99,100] ii) Inhibits T-cell activation and proliferation by suppressing NFκB, NFAT, and AP-1 [99,101,103] iii) Inhibits formation of memory T-cells through the activity of Akt and FoxO1 [102] |
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Pham, T.N.D.; Spaulding, C.; Munshi, H.G. Controlling TIME: How MNK Kinases Function to Shape Tumor Immunity. Cancers 2020, 12, 2096. https://doi.org/10.3390/cancers12082096
Pham TND, Spaulding C, Munshi HG. Controlling TIME: How MNK Kinases Function to Shape Tumor Immunity. Cancers. 2020; 12(8):2096. https://doi.org/10.3390/cancers12082096
Chicago/Turabian StylePham, Thao N.D., Christina Spaulding, and Hidayatullah G. Munshi. 2020. "Controlling TIME: How MNK Kinases Function to Shape Tumor Immunity" Cancers 12, no. 8: 2096. https://doi.org/10.3390/cancers12082096