Cancer cells do not merely consume energy; they redesign the body’s lipid economy to support uncontrolled growth and to weaken the immune response. A review by Koh, Lee, Kim and colleagues, published in Experimental & Molecular Medicine, examines how these processes are connected, describing lipid metabolism as a central biological system linking tumour progression with anti-cancer immunity. The article argues that fats and lipid-derived signals are not passive nutrients stored inside cells. They are structural components, energy sources and signalling molecules that can influence tumour-cell survival, immune-cell behaviour, inflammation and responses to treatment. This integrated view is drawing attention because therapies aimed at cancer metabolism may need to account for both the malignant cell and the immune ecosystem surrounding it.
Lipids include a broad family of molecules, ranging from fatty acids and triglycerides to cholesterol, phospholipids and sphingolipids. Tumour cells can increase the production of fatty acids through de novo lipogenesis, import lipids from the circulation or absorb them from neighbouring cells. Enzymes such as ATP-citrate lyase, acetyl-CoA carboxylase and fatty acid synthase help convert carbon from glucose and other nutrients into lipid building blocks. These molecules are then incorporated into cellular membranes, stored in lipid droplets or transformed into bioactive mediators. Because rapidly dividing cancer cells must create new membranes while maintaining energy production under stressful conditions, metabolic flexibility can provide a major survival advantage.
The tumour microenvironment intensifies this advantage. Cancer-associated fibroblasts, adipocytes, endothelial cells and immune cells exchange nutrients and signalling molecules with malignant cells. Adipose tissue, for example, can release free fatty acids that are taken up by tumours and oxidised in mitochondria to generate ATP. Lipid droplets can act as intracellular reserves, protecting fatty acids from toxic accumulation while making them available when oxygen or nutrients become scarce. In addition, hypoxia and other stresses within solid tumours can alter lipid synthesis and storage. These adaptations may help cancer cells continue to grow, invade surrounding tissues and resist chemotherapy, radiation or targeted treatment.
Lipid metabolism also affects the physical behaviour of tumours. Changes in membrane composition can influence receptor activity, vesicle trafficking and the formation of structures that enable migration and invasion. Cholesterol-rich membrane domains, often called lipid rafts, can organise growth-factor receptors and downstream signalling proteins, potentially strengthening pathways that promote proliferation. Fatty acids can also be converted into eicosanoids and other mediators that regulate inflammation, blood-vessel formation and tissue remodelling. Such signals may help establish conditions in which malignant cells move more efficiently through tissue and create new blood supplies, while simultaneously modifying how immune cells interpret the tumour.
The immune system is particularly sensitive to the lipid environment. T cells require carefully coordinated metabolic programmes when they become activated, multiply and attack abnormal cells. However, the tumour microenvironment is often poor in glucose and oxygen while containing excessive lipids, lactate and other metabolic by-products. Under these conditions, cytotoxic T cells and natural killer cells may lose functional capacity. Excessive lipid uptake or lipid peroxidation can damage immune-cell membranes and organelles, while changes in mitochondrial metabolism can reduce the production of molecules needed for effective killing. The result may be exhaustion, a state in which immune cells remain present but show diminished proliferation, cytokine production and cytotoxic activity.
Other immune populations can be reshaped in the opposite direction. Tumour-associated macrophages may accumulate lipids and adopt phenotypes that support tissue repair, angiogenesis and immune suppression rather than direct tumour destruction. Myeloid-derived suppressor cells can interfere with T-cell activation through nutrient competition, production of inhibitory molecules and modulation of inflammatory signalling. Regulatory T cells may be comparatively well adapted to the nutrient conditions within tumours, allowing them to persist and restrain anti-tumour responses. The review highlights the importance of viewing these populations as metabolically interconnected rather than analysing each immune cell in isolation. A lipid pathway that supports one cell type may impair another, producing complex effects across the tumour ecosystem.
Lipid-derived signals can also influence immune checkpoints and inflammatory networks. Oxidised lipids, prostaglandins and specialised sphingolipid metabolites can alter cytokine release, antigen presentation and the recruitment of immune cells. In some contexts, they promote chronic inflammation that helps cancer progression; in others, they suppress the signals required for an effective immune attack. This complexity helps explain why simply blocking lipid synthesis may not produce the same result in every tumour. The consequences may depend on cancer type, genetic background, diet, tissue location, oxygen availability and the composition of the surrounding immune population. A metabolic intervention could theoretically weaken malignant cells while improving immune function, but it might also create compensatory pathways that allow either cancer or immune cells to adapt.
These connections are relevant to modern immunotherapy. Immune-checkpoint inhibitors, including therapies targeting the PD-1, PD-L1 or CTLA-4 pathways, rely on the presence of immune cells capable of recovering anti-tumour activity. If those cells are metabolically paralysed by the tumour environment, releasing an inhibitory checkpoint may be insufficient. Researchers are therefore investigating combinations that pair immunotherapy with inhibitors of fatty-acid synthesis, lipid uptake, cholesterol handling or specific inflammatory pathways. Other approaches aim to reprogramme macrophages, reduce suppressive myeloid-cell activity or protect T-cell mitochondria. The challenge is achieving selective targeting: lipid metabolism is essential not only to tumours but also to normal tissues, immune surveillance and tissue repair.
The review also points toward the need for better biomarkers and more precise experimental tools. Measuring lipid metabolism from a single blood sample may not reveal what is occurring inside a tumour, where different regions can have sharply different nutrient conditions. Technologies such as lipidomics, spatial transcriptomics, single-cell sequencing and metabolic imaging can help map which cells produce, consume or transform particular lipids. These approaches could identify patients whose tumours depend on specific metabolic circuits or reveal why a treatment works in one cancer but fails in another. Yet translating such findings into clinical therapy will require careful attention to toxicity, drug delivery and the possibility that tumours reroute metabolism when one pathway is blocked.
By bringing cancer metabolism and anti-cancer immunity into the same framework, Koh and colleagues present lipids as potential therapeutic targets and as indicators of how tumours evolve under pressure. The central message is that malignant growth is not governed by tumour-cell genetics alone; it is also shaped by nutrient exchange and metabolic competition throughout the tumour microenvironment. Future treatments may therefore combine conventional anti-cancer drugs with strategies that remodel lipid availability, restore immune-cell fitness and prevent suppressive signalling. The field remains technically challenging, but understanding how fats function as fuel, membrane material and immune-regulatory messengers could open a new route toward therapies designed to attack cancer while strengthening the body’s own defences.
Subject of Research: The interplay between lipid metabolism, cancer progression and anti-cancer immunity
Article Title: The interplay between lipid metabolism, cancer progression and anti-cancer immunity
Article References: Koh, CH., Lee, Y., Kim, IK. et al. The interplay between lipid metabolism, cancer progression and anti-cancer immunity. Exp Mol Med (2026). https://doi.org/10.1038/s12276-026-01783-3
Image Credits: AI Generated
DOI: 10.1038/s12276-026-01783-3
