Related Experiment Video

Updated: Jan 26, 2026

Optimized Incorporation of Alkynyl Fatty Acid Analogs for the Detection of Fatty Acylated Proteins using Click Chemistry
07:27

Optimized Incorporation of Alkynyl Fatty Acid Analogs for the Detection of Fatty Acylated Proteins using Click Chemistry

Published on: April 9, 2021

6.0K

Fatty acid transport protein 2 reprograms neutrophils in cancer

Filippo Veglia1, Vladimir A Tyurin2, Maria Blasi3

  • 1Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA, USA.

Nature
|April 19, 2019
PubMed

Insights

Fatty acid transport protein 2 (FATP2) drives immunosuppressive functions in polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Inhibiting FATP2 selectively targets these cells, enhancing cancer therapy efficacy and delaying tumor progression.

Area of Science:

  • Immunology
  • Cancer Biology
  • Cellular Metabolism

Background:

  • Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are neutrophils implicated in cancer immune evasion and therapeutic resistance.
  • The precise mechanisms driving PMN-MDSC pathological activation remain incompletely understood, hindering targeted therapeutic strategies.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying PMN-MDSC immunosuppressive function.
  • To identify and validate a selective therapeutic target for PMN-MDSCs.

Main Methods:

  • Comparative analysis of gene expression in mouse and human PMN-MDSCs.
  • Investigated the role of fatty acid transport protein 2 (FATP2) in PMN-MDSC function using genetic deletion and pharmacological inhibition.
  • Assessed the impact of FATP2 modulation on tumor progression in preclinical models, including combination therapy with checkpoint inhibitors.

Main Results:

  • PMN-MDSCs exclusively upregulate FATP2, controlled by GM-CSF and STAT5 signaling.
  • FATP2 deletion abolished PMN-MDSC suppressive activity, primarily through regulating arachidonic acid uptake and prostaglandin E2 synthesis.
  • Pharmacological FATP2 inhibition abrogated PMN-MDSC function and significantly delayed tumor growth, with synergistic effects when combined with checkpoint inhibitors.

Conclusions:

  • FATP2 is essential for the immunosuppressive phenotype of PMN-MDSCs.
  • Selective FATP2 inhibition represents a promising strategy to disarm PMN-MDSCs and enhance cancer immunotherapy outcomes.

More Related Videos

Preparation, Purification, and Use of Fatty Acid-containing Liposomes10:43

Preparation, Purification, and Use of Fatty Acid-containing Liposomes

Published on: February 9, 2018

83.1K
Identification of Fatty Acids in Bacillus cereus08:41

Identification of Fatty Acids in Bacillus cereus

Published on: December 5, 2016

10.1K

Related Concept Videos

Overview of Fatty Acid Metabolism01:28

Overview of Fatty Acid Metabolism

Lipids also are sources of energy that power cellular processes. Like carbohydrates, lipids are composed of carbon, hydrogen, and oxygen, but these atoms are arranged differently. Most lipids are nonpolar and hydrophobic. Major types include fats and oils, waxes, phospholipids, and steroids.
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
36.8K
Protein Transport to the Thylakoids01:22

Protein Transport to the Thylakoids

Thylakoids are membrane-bound sac-like structures within the chloroplast that serve as sites for photosynthesis. Thylakoid lumen contains many electron transport proteins and is enclosed by a thylakoid membrane rich in the light-harvesting complex. Proteins targeted to the thylakoids are transported as precursors and are sorted by the general TOC/TIC import pathway. Once the precursor reaches the stroma, stromal processing peptidases remove their transit signal and expose thylakoid signal...
2.9K
Protein Transport to the Stroma01:24

Protein Transport to the Stroma

Chloroplasts are triple membrane structures with an outer membrane, an inner membrane, and a thylakoid membrane, each containing distinct metabolite transporters, membrane translocons, and enzymes. Appropriate sorting and translocating these proteins to their correct membrane systems is essential for chloroplast function.
Protein complexes called the translocon of the outer chloroplast membrane or TOC complex, and the translocon of the inner chloroplast membrane or TIC complex mediate the...
2.2K
Overview of Protein Sorting and Transport01:45

Overview of Protein Sorting and Transport

Eukaryotic cells have different membrane-bound organelles with distinct protein requirements. The process by which proteins are targeted to a specific organelle is called protein sorting.
Protein sorting can be of two types: signal-based sorting and vesicle-based trafficking. In signal-based sorting, specific amino acid sequences called sorting signals target proteins to the proper location inside the cell either via gated transport or by protein translocation.  In gated transport, folded...
22.2K
Protein Transport to the Inner Chloroplast Membrane01:18

Protein Transport to the Inner Chloroplast Membrane

Proteins targeted to the inner chloroplast membrane, or plastid proteins, are transported by two general pathways: the stop-transfer and the re-insertion or post-import pathways. Most plastid proteins carry N-terminal transit sequences and internal import sequences targeting it to the specific chloroplast subcompartment. Proteins targeted by the stop-transfer pathway have internal hydrophobic sequences that inhibit their translocation into the stroma. As a result, these precursors are arrested...
2.4K
Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
4.9K