Inhibitory effect of tumor cell-derived lactic acid on human T cells.

By Karin Fischer, P. Hoffmann, S. Voelkl, N. Meidenbauer, J. Ammer, M. Edinger, E. Gottfried, Sabine Schwarz, G. Rothe, S. Hoves and 7 more. Blood, 2007

1,805 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/6d0ba9cedb2f41e889ce58938a8ebcb47804a084

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Citations in the corpus

Lactate: a metabolic key player in cancer. (2011, background): “Recently, extracellular lactate was found to inhibit the differentiation of monocytes to dendritic cells (DC) and to inactivate the cytokine release from DCs (16) and cytotoxic T cells (17), the key player in antitumoral response.”
Foxp3 reprograms T cell metabolism to function in low glucose high lactate environments (2017, background): “…that Tregs are unable to form L-lactate, and that there is an effective turnover of L-lactate to pyruvate in Tregs—we hypothesized that Tregs may be able to withstand the strong suppressive effects that L-lactate has on effector and cytotoxic T cells (Calcinotto et al., 2012; Fischer et al., 2007).”
Targeting Metabolism to Improve the Tumor Microenvironment for Cancer Immunotherapy. (2020, background): “Lactic acid can inhibit effector T cell function through decreased proliferation and IFN-y production (Fischer et al., 2007; Mendler et al., 2012) and decrease the pH within the TME to further contribute to immune suppression.”
In Vitro Tumor Models: Advantages, Disadvantages, Variables, and Selecting the Right Platform (2016, background): “For example, the lactic acid-rich environment surrounding tumors inhibits the cytotoxic activity of T-lymphocytes (CTLs) (Fischer et al., 2007) and reduces the migration of monocytes (Gottfried et al.”
Lactate in the Regulation of Tumor Microenvironment and Therapeutic Approaches (2019, background): “A study quantified lactate levels in the serum of patients with different malignancies (lymphoid malignancies, myeloid malignancies, breast cancer, gastrointestinal cancer, urogenital cancer, sarcoma, lung cancer, melanoma and other types of cancer), finding high levels of lactate, furthermore, the ”
Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. (2011, positive): “Excreting high levels of lactate may support their survival, growth, and invasion by conditioning the tumor microenvironment (Koukourakis et al 2006), promoting tumor invasion (Gillies & Gatenby 2007, Swietach et al 2007), and suppressing anticancer T-cell immune response (Fischer et al 2007).”
Tumor cell metabolism: cancer's Achilles' heel. (2008, background): “, 2007), and suppress anticancer immune effectors (Fischer et al., 2007).”
Multicellular tumor spheroids: an underestimated tool is catching up again. (2010, methodology): “The pathophysiological environment thus critically contributes to ow many differences in biological functions compared to 2D cultures, including on of lactic acid that leads to defective responsiveness of TAA-specific CTLs to tumor ese include size measurements, penetrations studies, expression anal”
Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013, background): “lactate export by T cells, thus disrupting their ability to maintain glycolysis (121).”
LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells. (2016, background): “Based on our findings with human T cells (Fischer et al., 2007), we hypothesized that uptake of lactic acid by CD8+ T cells leads to intracellular acidification.”
Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions (2023, background): “5,(208) which inhibits CTL activation, proliferation, and cytokine production, and also triggers T cell apoptosis.(241) Hypoxia induces cancer cells to express chemokines such as CC chemokine ligand 28 (CCL28) to recruit regulatory T cells (Tregs).”
Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study (2020, background): “The severe type of COVID-19 patients had elevated blood lactic acid levels, which might suppress the proliferation of lymphocytes.(7) Multiple mechanisms mentioned above or beyond might work together to cause lymphopenia, and further research is needed.”
T Cell Dysfunction in Cancer (2018, background): “On the other hand, hypoxia induces increased expression and activity of the transcription factor hypoxiainducible factor 1α (HIF-1α), which promotes the expression of inhibitory receptors on T cells (Doedens et al., 2013), and leads to a reduction in T cell effector functions (Fischer et al., 2007).”