LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells.

By Almut Brand, K. Singer, G. Koehl, M. Kolitzus, Gabriele Schoenhammer, A. Thiel, Carina Matos, Christina Bruss, S. Klobuch, K. Peter and 29 more. Cell Metabolism, 2016

1,711 citations recorded by the source corpus.

Subfields: Biotechnology, Cancer Research, Immunology

View Paper: https://www.semanticscholar.org/paper/07a086e59ffa09dd092447a2fdbe7290a8a7bb2b

How researchers see this paper

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In Biotechnology

1. Alec C. Kimmelman
2. C. Lyssiotis

In Cancer Research

1. Michael D. Buck
2. Erika L. Pearce
3. Alec C. Kimmelman
4. S. Kaech
5. R. Sowell
6. B. Faubert
7. S. Kierans
8. J. Cleveland

In Immunology

1. Michael D. Buck
2. S. Kaech
3. R. Sowell
4. Erika L. Pearce
5. Alec C. Kimmelman
6. Rafi Ahmed
7. E. Wherry
8. M. Bevan

Citations in the corpus

• Lactate metabolism in human lung tumors (2017, positive): “Evidence indicates that lactate in the microenvironment modulates immune cell function and promotes invasion and metastasis, implicating tumor glycolysis and lactate secretion in processes that impact cancer-related mortality (Brand et al., 2016; Rizwan et al., 2013; Xie et al., 2014).”
• Systems analysis of intracellular pH vulnerabilities for cancer therapy (2018, methodology): “…acidosis on several processes, including the induction of growth factors (e.g., VEGF via HIF1 α ), using secreted lactic acid as a nutrient source 15 , suppression of immune surveillance 16 – 18 , and evolutionary selection for acid-resistant malignant cells in the tumor microenvironment 19 – 21 .”
• Lactate in the Regulation of Tumor Microenvironment and Therapeutic Approaches (2019, background): “This because lactate concentrations above 20mMcaused the apoptosis of T andNK cells, whichmay explain smaller proportions of T cells and NK cells in tumors with higher concentrations of lactate (159).”
• The Acidic Tumor Microenvironment as a Driver of Cancer. (2019, background): “Natural killer cells are also sensitive to low pHo and lactic acid that together reduce their tumor infiltration and activity (147, 148).”
• Metabolic Instruction of Immunity (2017, positive): “In addition to signals received from TIL IFN-γ (Noman et al., 2014), HIF-1α also induces the expression of the suppressive ligand PD-L1 in tumor cells, TAMs, and myeloid-derived suppressor cells (MDSCs), and this can lead to TIL suppression via PD-1 (Figure 1).”
• Metabolic Interactions in the Tumor Microenvironment (2017, background): “In melanoma, lactate suppresses natural killer and T cell anti-tumor immune responses [20, 101, 102].”
• Regulation of glycolysis by the hypoxia‐inducible factor (HIF): implications for cellular physiology (2020, background): “Finally, lactate inhibits the activation and survival of natural killer cells in both in vitro and in vivo settings (Brand et al. 2016).”