ArticleCancer cell2023
MCT4-dependent lactate secretion suppresses antitumor immunity in LKB1-deficient lung adenocarcinoma.
Article in Cancer cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 2 of them syntheses that pooled it.
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Who cites it
131 citing papers in PubMed, 2 syntheses or guidelines pooled it, 157 citations in OpenAlex.
- Research trends on lactate in cancer: a bibliometric analysis and comprehensive review (2015-2024).Frontiers in immunology · 2025Pooled it
- Lactylation and its roles in diseases: a systematic bibliometric exploration of the research landscape.Frontiers in oncology · 2025Pooled it
- Tislelizumab (anti-PD-1) plus chemotherapy as neoadjuvant therapy for patients with stage IB3/IIA2 cervical cancer (NATIC): a prospective, single-arm, phase II study.Signal transduction and targeted therapy · 2025Trial
- Senescent-Like Neutrophils Shape Angiogenic Immunosuppressive Niches in Colorectal Cancer Liver Metastasis.Cancer discovery · 2026Article
- Research progress on lactate metabolism in lung cancer: Tumorigenesis, drug resistance and clinical translation (Review).Oncology reports · 2026Review
- A pathomics model for predicting lactate-related prognostic risk groups and their biological mechanisms in lung adenocarcinoma.Translational cancer research · 2026Article
- Molecular insights and therapeutic implications for the tumor suppressor role of LKB1 in non-small cell lung cancer.Cancer letters · 2026Review
- KRAS/ERK2-driven stabilization of AARS1 reprograms tumor metabolism and confers Sorafenib resistance in lung adenocarcinoma.Cell death and differentiation · 2026Article
- MiR-1976 affects lung squamous cell carcinoma development by targeting NCAPH.Journal of applied genetics · 2026Article
- The Cancer Cell Metabolic Reprogramming Remodels the Tumor Microenvironment: Molecular Mechanisms and Therapeutic Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Article
- Review
- Metabolic reprogramming of myeloid cells in cancer: from lactate-NAMPT axis to AI-guided therapeutics.Experimental & molecular medicine · 2026Review
- Molecular classification identifies aggressive gastrointestinal stromal tumor subtype targetable by PARP inhibitors.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Beyond a waste product: lactate as a master metabolite dictating anti-tumor T-cell fate.Cell death & disease · 2026Review
- Lactate-Primed NETosis Modulates Hepatic Regeneration During Acute Liver Failure via the TLR9/KLF15/AJUBA Axis.Cell proliferation · 2026Article
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Solute carrier transporters as metabolic gatekeepers in tumor-microenvironment crosstalk.Acta pharmacologica Sinica · 2026Review
- Lactate reprograms PGE2 metabolism via GPR81 inhibits COX2 to relieved psoriasis.Scientific reports · 2026Article
- LDHA-driven lactate metabolism promotes MDSC activation and immunosuppressive microenvironment in prostate cancer.Oncogene · 2026Article
71 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 10 institutions in 1 country.
Funding
Abstract
Inactivating STK11/LKB1 mutations are genomic drivers of primary resistance to immunotherapy in KRAS-mutated lung adenocarcinoma (LUAD), although the underlying mechanisms remain unelucidated. We find that LKB1 loss results in enhanced lactate production and secretion via the MCT4 transporter. Single-cell RNA profiling of murine models indicates that LKB1-deficient tumors have increased M2 macrophage polarization and hypofunctional T cells, effects that could be recapitulated by the addition of exogenous lactate and abrogated by MCT4 knockdown or therapeutic blockade of the lactate receptor GPR81 expressed on immune cells. Furthermore, MCT4 knockout reverses the resistance to PD-1 blockade induced by LKB1 loss in syngeneic murine models. Finally, tumors from STK11/LKB1 mutant LUAD patients demonstrate a similar phenotype of enhanced M2-macrophages polarization and hypofunctional T cells. These data provide evidence that lactate suppresses antitumor immunity and therapeutic targeting of this pathway is a promising strategy to reversing immunotherapy resistance in STK11/LKB1 mutant LUAD.
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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.