Mendler, Anna N. and Hu, Bin and Prinz, Petra U. and Kreutz, Marina and Gottfried, Eva and Noessner, Elfriede (2012) Tumor lactic acidosis suppresses CTL function by inhibition of p38 and JNK/c-Jun activation. INTERNATIONAL JOURNAL OF CANCER, 131 (3). pp. 633-640. ISSN 0020-7136,
Full text not available from this repository. (Request a copy)Abstract
Lactic acidosis is common to most solid tumors and has been found to affect infiltrating immune cells. Here we document effector phase inhibition of cytotoxic T cells (CTLs) involving complete blockage of cytokine production and partial impairment of lytic granule exocytosis. Lactic acidosis impaired TCR-triggered phosphorylation of JNK, c-Jun and p38, while not affecting MEK1 and ERK. The select targeting of signaling proteins involved in IFN? production (JNK/c-Jun, p38) without affecting those jointly used in cytokine regulation and granule exocytosis (MEK1/ERK) explains the observed split effect of lactic acidosis on the CTL responses. CTL inhibition by lactic acidosis showed fast dynamics with immediate onset and reversion. Functional recovery by neutralizing the extracellular pH despite continuous presence of lactate holds promise that CTL activity can be improved in the milieu of solid tumors with appropriate anti-acidosis treatment, thereby increasing the efficacy of adoptive T cell therapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CD8(+) T-CELLS; INFILTRATING LYMPHOCYTES; IMMUNE-RESPONSE; METASTASES; CARCINOMA; CANCERS; PH; effector phase inhibition; lactic acid; T cell receptor signaling; adoptive T cell therapy; cytotoxic T cells |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 May 2020 06:14 |
| Last Modified: | 08 May 2020 06:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18418 |
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