Related Experiment Video

Updated: Jan 9, 2026

Radiosynthesis of 1-2-[18F]Fluoroethyl-L-Tryptophan using a One-pot, Two-step Protocol
08:33

Radiosynthesis of 1-2-[18F]Fluoroethyl-L-Tryptophan using a One-pot, Two-step Protocol

Published on: September 21, 2021

3.5K

Revisiting tryptophan metabolism in cancer: complexity, context, and spatial heterogeneity

Teng Teng Xu1, Camille Guyot1, Peter J Murray1

  • 1Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, Martinsried 82142, Germany.

Current Opinion in Immunology
|December 10, 2025
PubMed

Insights

Tryptophan metabolism in cancer is complex, involving spatial niches that impact T cell immunity. Understanding these niches is key for developing new cancer therapies beyond IDO1 inhibition.

Area of Science:

  • Oncology
  • Immunology
  • Metabolic pathways

Background:

  • Tryptophan (TRP) metabolism, particularly the kynurenine pathway via indoleamine-2,3-dioxygenase 1 (IDO1) and tryptophan-2,3-dioxygenase (TDO2), has been linked to cancer immunity by impairing anti-tumor T cell function.
  • Previous therapeutic strategies targeting IDO1/TDO2 have failed in clinical trials, suggesting a more complex role for TRP metabolism in tumors.

Purpose of the Study:

  • To review emerging insights into the diverse and spatially defined functions of TRP metabolism within the tumor microenvironment.
  • To discuss how spatial profiling technologies can advance our understanding of TRP metabolism's role in cancer immunity.

Main Methods:

  • Synthesis of recent research on TRP metabolism in cancer.
  • Discussion of advances in spatial profiling techniques and their application to metabolic enzyme distribution.
  • Analysis of how spatial heterogeneity in TRP-metabolizing enzymes influences immune responses.

Main Results:

  • TRP-depleting enzymes exhibit dual, context-dependent roles in cancer immunity.
  • TRP-metabolizing enzymes form distinct spatial niches within tumors, not uniform expression.
  • Spatial profiling reveals localized TRP availability, metabolite gradients, and immune modulation within these niches.

Conclusions:

  • TRP metabolism's role in cancer immunity is more intricate than previously understood, with significant spatial variations.
  • Spatial omics approaches are crucial for deciphering the complex metabolic landscape of tumors.
  • Integrating spatial insights may pave the way for novel cancer therapeutics that move beyond simple IDO1 inhibition.

More Related Videos

Simultaneous Quantification of Selected Kynurenines Analyzed by Liquid Chromatography-Mass Spectrometry in Medium Collected from Cancer Cell Cultures10:38

Simultaneous Quantification of Selected Kynurenines Analyzed by Liquid Chromatography-Mass Spectrometry in Medium Collected from Cancer Cell Cultures

Published on: May 9, 2020

3.7K
Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors08:08

Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors

Published on: February 27, 2015

16.9K

Related Concept Videos

Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.9K
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.6K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.7K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.8K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.3K