Related Experiment Video

Updated: Feb 1, 2026

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
08:38

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS

Published on: November 8, 2015

17.5K

Potent immunosuppressive effects of the oncometabolite R-2-hydroxyglutarate

Lorenzo Galluzzi1,2,3, Guido Kroemer4,5,6,7,8,9,10

  • 1Department of Radiation Oncology, Weill Cornell Medical College, New York, US.

Oncoimmunology
|December 8, 2018
PubMed

Insights

Mutations in isocitrate dehydrogenase (IDH) enzymes drive cancer by producing the oncometabolite R-2-hydroxyglutarate (R-2-HG). This metabolite also suppresses anti-cancer T cell responses, suggesting dual therapeutic potential for IDH inhibitors.

Area of Science:

  • Biochemistry
  • Oncology
  • Immunology

Background:

  • Somatic gain-of-function mutations in isocitrate dehydrogenase (NADP(+)) 1 (IDH1) and isocitrate dehydrogenase (NADP(+)) 2 (IDH2) are key drivers in acute myeloid leukemia and glioma.
  • These mutations lead to the production of the oncometabolite R-2-hydroxyglutarate (R-2-HG), which has significant epigenetic effects within cancer cells.

Discussion:

  • Extracellular R-2-HG, released by malignant cells, can be absorbed by T lymphocytes.
  • This uptake impairs the ability of T lymphocytes to mount effective anti-cancer immune responses, highlighting R-2-HG's immunosuppressive role.
  • R-2-HG contributes to oncogenesis and tumor progression through both cell-autonomous epigenetic modification and systemic immunosuppression.

Key Insights:

  • Mutant IDH enzymes produce R-2-HG, a metabolite that promotes cancer and suppresses anti-tumor immunity.
  • R-2-HG acts as an oncometabolite affecting cancer cell epigenetics and also as an immunosuppressive factor.
  • Targeting mutant IDH1 and IDH2 offers a dual therapeutic strategy against cancer and its associated immune suppression.

Outlook:

  • Clinical evaluation of chemical inhibitors targeting mutant IDH1 and IDH2 is ongoing.
  • These inhibitors hold promise for dual therapeutic effects: directly impacting cancer cells and alleviating R-2-HG-induced immunosuppression.
  • Future research may focus on optimizing these inhibitors for comprehensive cancer treatment by addressing both oncogenic and immunosuppressive mechanisms.
Keywords:
HIF-1αcancer-associated fibroblastscytotoxic T lymphocytesimmunosurveillanceimmunotherapyivosidenib

More Related Videos

Methods to Evaluate Cytotoxicity and Immunosuppression of Combustible Tobacco Product Preparations09:25

Methods to Evaluate Cytotoxicity and Immunosuppression of Combustible Tobacco Product Preparations

Published on: January 10, 2015

11.9K
Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice08:06

Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice

Published on: November 27, 2019

9.6K

Related Concept Videos

Buffer Effectiveness02:19

Buffer Effectiveness

Buffer solutions do not have an unlimited capacity to keep the pH relatively constant . Instead, the ability of a buffer solution to resist changes in pH relies on the presence of appreciable amounts of its conjugate weak acid-base pair. When enough strong acid or base is added to substantially lower the concentration of either member of the buffer pair, the buffering action within the solution is compromised.
The buffer capacity is the amount of acid or base that can be added to a given volume...
55.2K
Framing Effects03:26

Framing Effects

Information is everywhere and its presentation—such as how and when items are presented—can impact our perceptions and decisions surrounding the info. This broad concept umbrellas framing effects—influences that occur due to the way information is framed in its appearance, whether it’s purely the order or the specific wording of a message. Let’s take a look at numerous ways in which two versions of something can objectively say the same thing, yet we respond in...
7.9K
meta-Directing Deactivators: –NO2, –CN, –CHO, –⁠CO2R, –COR, –CO2H01:13

meta-Directing Deactivators: –NO2, –CN, –CHO, –⁠CO2R, –COR, –CO2H

All meta-directing substituents are deactivating groups. These substituents withdraw electrons from the aromatic ring, making the ring less reactive toward electrophilic substitution. For example, the nitration of nitrobenzene is 100,000 times slower than that of benzene because of the deactivating effect of the nitro group. The first step in an electrophilic aromatic substitution is the addition of an electrophile to form a resonance-stabilized carbocation. The energy diagrams for...
6.7K
Biological Effects of Radiation02:59

Biological Effects of Radiation

All radioactive nuclides emit high-energy particles or electromagnetic waves. When this radiation encounters living cells, it can cause heating, break chemical bonds, or ionize molecules. The most serious biological damage results when these radioactive emissions fragment or ionize molecules. For example, α and β particles emitted from nuclear decay reactions possess much higher energies than ordinary chemical bond energies. When these particles strike and penetrate matter, they...
17.9K
2° Amines to N-Nitrosamines: Reaction with NaNO201:20

2° Amines to N-Nitrosamines: Reaction with NaNO2

Secondary amines react with nitrous acid to form N-nitrosamines, as depicted in Figure 1. Nitrous acid, a weak and unstable acid, is formed in situ from an aqueous solution of sodium nitrite and strong acids, such as hydrochloric acid or sulfuric acid, in cold conditions. In the presence of an acid, the nitrous acid gets protonated. The subsequent loss of water results in the formation of the electrophile known as nitrosonium ion.
5.5K
Effects of feedback01:24

Effects of feedback

Feedback in control systems plays a critical role in shaping various operational parameters, extending beyond simple error reduction to influence stability, bandwidth, gain, impedance, and sensitivity. Understanding these effects requires examining a basic feedback system characterized by defined input, output, error, and feedback signals.
Feedback significantly modifies the gain of a control system. The gain of a system without feedback is altered by a factor of one plus GH, where G represents...
1.0K