ArticleJCI insight2022
Inhibition of MNKs promotes macrophage immunosuppressive phenotype to limit CD8+ T cell antitumor immunity.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Novel approaches to modulate CAR-T cell function by targeting the tumor microenvironment in ovarian cancer.Journal of ovarian research · 2026Review
- Preoperative exercise induces anti-tumor Kupffer cells to prevent surgical stress-promoted colorectal cancer liver metastasis.Cell reports. Medicine · 2026Article
- Radiotherapy induces YTHDF2 in dendritic cells impairing cross-presentation and T cell function.The Journal of experimental medicine · 2026Article
- HERV-K TM Subunit Elicits CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrated bioinformatics analysis identifies cuproptosis and ferroptosis gene signatures via subgroup clustering: Prognostic and therapeutic implications in breast cancer.Biochemistry and biophysics reports · 2025Article
- Lack of phospho-eIF4E worsens experimental colitis by inhibiting Treg suppressive activity.Journal of inflammation (London, England) · 2025Article
- Multiomics Investigation of Exhausted T Cells in Glioblastoma Tumor Microenvironment:International journal of molecular sciences · 2025Article
- A signature based on efferocytosis-related genes for the evaluation of prognosis and the tumour microenvironment in gastric cancer.Scientific reports · 2025Article
- Regorafenib induces DNA damage and enhances PARP inhibitor efficacy in pancreatic ductal carcinoma.BMC cancer · 2024Article
- Trametinib Potentiates Anti-PD-1 Efficacy in Tumors Established from Chemotherapy-Primed Pancreatic Cancer Cells.Molecular cancer therapeutics · 2024Article
- Targeting BCL2 with Venetoclax Enhances the Efficacy of the KRASG12D Inhibitor MRTX1133 in Pancreatic Cancer.Cancer research · 2024Article
- Killing capacity analysis of tumor-infiltrating cytotoxic lymphocytes and impact on lymph node metastasis in differentiated papillary carcinoma of thyroid with the BRAF V600E mutation.Diagnostic pathology · 2024Article
- Subtype-specific human endogenous retrovirus K102 envelope protein is a novel serum immunosuppressive biomarker of cancer.Frontiers in immunology · 2024Article
- Unveiling the immunosuppressive landscape of pancreatic ductal adenocarcinoma: implications for innovative immunotherapy strategies.Frontiers in oncology · 2024Review
- Article
- Genome-scale modeling predicts metabolic differences between macrophage subtypes in colorectal cancer.iScience · 2023Article
- The role of eIF4F-driven mRNA translation in regulating the tumour microenvironment.Nature reviews. Cancer · 2023Review
- Using Imidazo[2,1-ACS medicinal chemistry letters · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
To elicit effective antitumor responses, CD8+ T cells need to infiltrate tumors and sustain their effector function within the immunosuppressive tumor microenvironment (TME). Here, we evaluate the role of MNK activity in regulating CD8+ T cell infiltration and antitumor activity in pancreatic and thyroid tumors. We first show that human pancreatic and thyroid tumors with increased MNK activity are associated with decreased infiltration by CD8+ T cells. We then show that, while MNK inhibitors increase CD8+ T cells in these tumors, they induce a T cell exhaustion phenotype in the tumor microenvironment. Mechanistically, we show that the exhaustion phenotype is not caused by upregulation of programmed cell death ligand 1 (PD-L1) but is caused by tumor-associated macrophages (TAMs) becoming more immunosuppressive following MNK inhibitor treatment. Reversal of CD8+ T cell exhaustion by an anti-PD-1 antibody or TAM depletion synergizes with MNK inhibitors to control tumor growth and prolong animal survival. Importantly, we show in ex vivo human pancreatic tumor slice cultures that MNK inhibitors increase the expression of markers associated with immunosuppressive TAMs. Together, these findings demonstrate a role of MNKs modulating a protumoral phenotype in macrophages and identify combination regimens involving MNK inhibitors to enhance antitumor immune responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.