Far from being mere cellular building blocks, amino acids have emerged as powerful regulators of cancer growth and immune function.

This review reveals how tumours manipulate amino acid metabolism to gain a competitive edge, starving immune cells and reshaping the tumour immune microenvironment (TIME).

Key players such as glutamine, arginine, tryptophan, and methionine are now recognised not only as fuel but also as signalling agents that modulate immunity and therapeutic resistance.

The study also outlines innovative strategies—from enzyme inhibitors to engineered probiotics—that leverage this metabolic vulnerability to reprogram the TIME and enhance anti-cancer immunity.

The tumour microenvironment is not just a site of cancer growth—it is a high-stakes metabolic contest where tumour and immune cells vie for limited resources.

Amino acids, once seen as passive nutrients, are now known to steer cell fate, immune suppression, and resistance to immunotherapy.

Tumours often win this battle by monopolising amino acids, crippling the metabolism of nearby T cells and macrophages.

Recent advances have illuminated how this biochemical imbalance hinders immune surveillance and fosters tumour progression.

Due to these challenges, there is a growing urgency to explore how amino acid dynamics influence cancer immunity and identify new therapeutic targets within this hidden battleground.

In a new review published in Cancer Biology & Medicine, scientists from Tongji University Cancer Centre explored how amino acid metabolism governs the intricate dialogue between cancer cells and immune defences.

The paper charts a comprehensive map of how amino acid sensing, transport, and utilisation shape tumour behaviour and immune cell function.

It also highlights pioneering therapies—from CAR-T cell enhancements to microbial-based interventions—that rewire the tumour immune microenvironment (TIME) and offer fresh hope in the fight against cancer.

Tumour cells and immune cells are locked in a biochemical tug-of-war over amino acids.

The review uncovers how tumours exploit this metabolic dependency to fuel their growth while sabotaging immune responses.

Glutamine feeds tumour proliferation but its depletion cripples T cells.

Arginine, essential for T cell activation, is often depleted in the TIME by tumour-associated macrophages expressing arginase.

Tryptophan is converted by tumour enzymes into kynurenine, suppressing T cells via the AhR pathway.

Methionine, vital for DNA methylation, is hoarded by cancer cells, disrupting T cell epigenetic programming.

Beyond nutrient supply, amino acids act as molecular messengers.

Sensors such as mTOR, AMPK, and AhR decode amino acid levels, triggering survival and immune evasion pathways.

Newly discovered sensors like TARS2 and HDAC6 open doors to uncharted therapeutic targets.

The review further highlights experimental interventions—from enzyme inhibitors and amino acid-loaded nanoparticles to diet-based and microbiota-driven strategies—that selectively reprogram metabolism to favour immune activation.

These findings connect molecular pathways to real-world treatments, positioning amino acid metabolism as a powerful lever in cancer therapy.

"Amino acids are not just nutrients—they are the language tumours and immune cells use to communicate," said Dr. Ping Wang, co-corresponding author of the review.

"By understanding this metabolic dialogue, we can begin to intercept and rewrite it. Our work lays the foundation for a new class of therapies that don't just kill cancer cells but also empower the immune system to fight back more effectively."

Targeting amino acid metabolism offers a novel and precise strategy to tip the balance of the tumour immune microenvironment.

Therapeutic approaches such as glutaminase inhibitors, arginase blockers, and methionine restriction diets are being tested alongside immune checkpoint inhibitors to amplify antitumor effects.

Probiotic-based therapies that alter local amino acid levels and engineered immune cells with enhanced nutrient-sensing capacities hold promise for hard-to-treat cancers.

As metabolic profiling becomes integrated into oncology, these amino acid-centred interventions may lead to more personalised, effective cancer treatments that overcome immune resistance and improve patient survival.

Source: China Anti-Cancer Association