What Is the Tumor Microenvironment and How Does It Help Cancer Grow?
A tumor is not just a lump of cancer cells. Cancer cells live among normal cells, blood vessels, protein fibers and chemical signals, and these surroundings are called the tumor microenvironment. Cancer cells change their surroundings so that they feed the tumor, shield it from the immune system, help it spread and protect it from treatment.
By Chris Morais, MSc, MPhil, PhD
Published
The tumor microenvironment is everything around the cancer cells in a tumor: normal cells such as fibroblasts and immune cells, blood vessels, a mesh of proteins, and the signals they exchange. Cancer cells reprogram these parts to bring in food and oxygen, block immune attack, help cancer spread and protect the tumor from treatment.
- What Is the Tumor Microenvironment?
- Which Cells Are in the Tumor Microenvironment?
- How Do Cancer Cells Recruit Normal Cells to Help Them?
- Why Are Parts of a Tumor Low in Oxygen and Acidic?
- How Does the Tumor Microenvironment Help Cancer Spread?
- How Does the Tumor Microenvironment Protect Cancer From Treatment?
- Does the Tumor Microenvironment Change as Cancer Grows?
- Can Treatments Target the Tumor Microenvironment?
- Frequently Asked Questions
What Is the Tumor Microenvironment?
The tumor microenvironment is the mix of normal cells, blood vessels, supporting material and chemical signals that surrounds cancer cells inside a tumor[1],[2]. Scientists once studied tumors mainly as masses of cancer cells. Today they see the surroundings as an active part of the disease that helps cancer grow, not a silent bystander[1].
The tumor microenvironment has five main parts:
- Normal cells. These include fibroblasts, immune cells and the cells that line blood vessels[2].
- Blood vessels. These bring oxygen and food into the tumor and carry waste away[1].
- The extracellular matrix. This is the mesh of proteins, such as collagen, that fills the spaces between cells and holds tissue together[2]. It gives the tumor its shape, and it also stores growth signals that cells can release later[1].
- Chemical signals. Cells send messages to each other using proteins such as growth factors and cytokines. They also send tiny bubbles called exosomes, which carry proteins and genetic material from one cell to another[2].
- Living conditions. These include the amount of oxygen, food and acid around the cells. In many tumors, these conditions are harsh[1],[2].
Is the tumor microenvironment made only by cancer cells? No. Most of the cells in the tumor microenvironment are normal cells from the body. Some were already living in the tissue where the cancer started, and others were drawn in from nearby tissue or from the blood[1]. Cancer cells do not build these parts themselves. Instead, they send signals that change how normal cells behave[1],[2]. The cancer cells shape their surroundings, and the surroundings in turn shape the cancer cells. This two-way link starts early in tumor growth and continues as the cancer develops[1].
Which Cells Are in the Tumor Microenvironment?
The main cells in the tumor microenvironment are fibroblasts, immune cells and the cells that form blood vessels. Some organs also add their own cell types, such as fat cells in the breast[1],[2].
The table below shows the main cell types, their usual job in healthy tissue, and what they can do inside a tumor[1],[2].
| Cell type | Usual job in healthy tissue | What it can do in a tumor |
|---|---|---|
| Fibroblasts | Make and repair the supporting mesh of tissue | Build a stiff mesh, release growth signals and help block drugs and immune cells |
| Killer T cells | Find and destroy infected or abnormal cells | Attack cancer cells, but are often kept out or switched off |
| Regulatory T cells | Stop immune responses from going too far | Calm the immune attack on the tumor |
| Macrophages | Eat germs and debris and help wounds heal | Can switch to a helper type that supports growth, new blood vessels and spread |
| Endothelial cells | Line the inside of blood vessels | Form new, leaky blood vessels that feed the tumor |
| Fat cells | Store energy | In some cancers, release fats that cancer cells use as fuel |
Immune cells can work for or against the tumor. Killer T cells can destroy cancer cells. Regulatory T cells calm the immune response, and macrophages can switch to a type that helps the tumor instead of fighting it[1]. Tumors use these helper cells to switch off the immune attack around them. That process is explained in How Do Cancer Cells Hide from the Immune System?
Endothelial cells line the blood vessels. When a tumor grows, these cells form new blood vessels to feed it. Tumor blood vessels are often immature and leaky[1]. How tumors build their own blood supply is explained in Why Do Tumors Need New Blood Vessels? Angiogenesis Explained. Cells called pericytes wrap around these vessels and help support them[2].
Other support cells depend on where the cancer is. In breast cancer, nearby fat cells can release fats that cancer cells use for energy. In the liver and pancreas, cells called stellate cells can help build the dense, scar-like tissue seen in some tumors, such as pancreatic cancer[1].
What Do Cancer-Associated Fibroblasts Do?
Cancer-associated fibroblasts are fibroblasts that have been switched on by cancer cells, and they help the tumor grow, spread and survive[1],[2]. They are a major part of the supporting tissue in many tumors[1].
In healthy tissue, fibroblasts become active to repair a wound and then settle down again once the wound heals. Near a tumor, they stay switched on. Cancer-associated fibroblasts help the tumor in several ways:
- They build and reshape the matrix. They are the main source of the protein mesh around cancer cells[2]. This mesh can become dense and stiff.
- They release growth signals. These signals help cancer cells survive, divide and move[2].
- They help grow new blood vessels. They release signals, such as VEGF, that tell blood vessels to grow toward the tumor[2].
- They weaken the immune attack. They can draw in immune cells that calm the immune response instead of attacking the cancer[2].
- They feed cancer cells. They can supply nutrients that cancer cells use for energy[2].
- They help protect cancer cells from treatment. They release signals that make cancer cells harder to kill with drugs[5].
Cancer-associated fibroblasts are not all the same. They can come from different starting cells, and some types may even slow a tumor down rather than help it[2]. This is one reason researchers are working to understand them better before trying to target them with drugs.
How Do Cancer Cells Recruit Normal Cells to Help Them?
Cancer cells recruit normal cells by releasing chemical signals that call cells in from nearby tissue and the blood, and then change how those cells behave[1],[2]. Cancer cells use these normal cells for their own benefit[2].
Recruitment happens in several ways:
- Calling cells in. Cancer cells release signals that attract fibroblasts and immune cells into the tumor[2].
- Changing their behavior. Cancer cells release signals, such as TGF-beta and PDGF, that turn ordinary fibroblasts into cancer-associated fibroblasts. Other signals push macrophages toward the helper type that supports the tumor[1].
- Sending packages. Cancer cells release exosomes. These tiny bubbles carry proteins and genetic material into normal cells and change how those cells work[1],[2].
- Asking for more help under stress. When cancer cells face low oxygen, a lack of food, acidity or chemotherapy, they can recruit more normal cells and reshape the matrix to make their surroundings easier to live in[2].
Once normal cells are recruited, they release their own signals. For example, macrophages in a tumor can release signals that help cancer cells change shape and become better at moving[2]. These signals help the cancer cells grow, and the growing cancer cells then send out more signals. This back-and-forth keeps the tumor microenvironment working in the cancer's favor[1].
Many of the signals cancer cells use are the same ones the body uses to heal wounds. The normal cells are not "fooled" in a conscious way. They simply respond to the signals they receive, just as they would in healthy tissue.
Why Are Parts of a Tumor Low in Oxygen and Acidic?
Parts of a tumor are low in oxygen because the tumor grows faster than its blood supply, and they are acidic because cancer cells make a lot of acid waste that poor blood flow cannot remove[1],[3],[4]. Low oxygen is called hypoxia. Studies have shown that hypoxia is present in about 90% of solid tumors[3].
Oxygen can only travel a short distance from a blood vessel into tissue. Cells that are more than about 100 to 200 micrometers (0.1 to 0.2 millimeters) from a working blood vessel may not get enough oxygen[3]. Once a tumor grows to about 1 to 2 cubic millimeters, parts of it begin to run short of oxygen[1].
The tumor responds by growing new blood vessels, but these vessels are poorly built. They are twisted, leaky and uneven. They can also be squeezed by the growing tumor or blocked by clots[2],[3]. As a result, blood flow through the tumor is patchy.
Low oxygen can happen in two ways[3]:
- Long-lasting low oxygen. Cells far from any blood vessel are short of oxygen all the time.
- Short bursts of low oxygen. Cells closer to vessels can lose oxygen for short periods when blood flow slows or stops, then get it back.
Cells short of oxygen switch on a protein called HIF (hypoxia-inducible factor). HIF turns on genes that help cells survive with little oxygen, use more sugar and call for new blood vessels[3].
Cancer cells break down large amounts of sugar for energy, even when oxygen is present. This process makes lactate (lactic acid) and other acid waste[3],[4]. It is known as the Warburg effect, which is explained in Why Do Cancer Cells Keep Growing?
Cancer cells pump this acid out so their insides stay close to neutral. The acid then collects in the fluid around them[3],[5]. Because blood flow is poor, the acid is not washed away[4]. Studies have shown that lactate levels in tumors can be up to about ten times higher than in healthy tissue. The fluid around tumor cells can reach a pH of about 6.0 to 6.5, which is clearly acidic[4].
Low oxygen and acidity are hard on cells, but they do not stop cancer. Instead, they favor the toughest cancer cells. Low oxygen can select cancer cells that are better at avoiding cell death[3]. Low oxygen and acid also weaken immune cells, help cancer spread and make treatment less effective, as the next sections explain[3],[4],[5]. Oxygen and acid levels also differ from one part of a tumor to another. This is one reason cells within the same tumor can be so different, as explained in Why Are Cancer Cells Within the Same Tumor Different?
How Does the Tumor Microenvironment Help Cancer Spread?
The tumor microenvironment helps cancer spread by sending signals that make cancer cells move, opening paths through tissue, offering leaky blood vessels to enter, and preparing distant organs[1],[2]. The full journey of spreading cancer cells is explained in How Does Cancer Spread to Other Parts of the Body? This section focuses on how the surroundings help.
- Low oxygen pushes cells to move. HIF switches on genes that help cancer cells invade nearby tissue and spread[3]. Low oxygen also helps cancer cells loosen their grip on neighboring cells and change into a more mobile shape[3].
- Acid helps invasion. An acidic environment favors invasion and spread[4].
- The matrix can be a wall or a gate. The protein mesh can block cancer cells, but enzymes can cut through it and open a path[2]. When the mesh is broken down, it also releases stored growth signals[1].
- Macrophages help cancer cells escape. Helper macrophages release signals that help cancer cells invade nearby tissue and spread[2].
- Leaky vessels are easier to cross. Cancer cells can pass through the walls of blood vessels to enter the blood. Immature, leaky vessels make it easier for cancer cells to cross vessel walls[1].
- Distant organs are prepared in advance. Exosomes released by the tumor can travel to other organs and change the cells there, making those places easier for cancer cells to settle in[2].
How Does the Tumor Microenvironment Protect Cancer From Treatment?
The tumor microenvironment protects cancer from treatment by keeping drugs from reaching cancer cells, making cancer cells harder to kill, and switching off the immune attack[2],[5]. Researchers call this environment-based resistance. It is different from resistance caused by changes inside the cancer cells themselves, which is explained in Why Does Cancer Treatment Sometimes Stop Working?
The surroundings protect cancer in five main ways.
1. Drugs cannot reach every cancer cell. Leaky, uneven blood vessels deliver drugs poorly to some parts of the tumor[5]. Fluid pressure inside many tumors is high, and this pressure makes it harder for drugs to move in, especially large drug molecules[2],[5]. A dense, stiff matrix also acts as a physical barrier[2],[5].
2. Low oxygen weakens treatment. Radiation therapy works less well where oxygen is low. This is because radiation needs oxygen to damage cancer cells fully[3]. Low oxygen also makes cancer cells less likely to die after chemotherapy[5].
3. Acid keeps some drugs out. Acid changes how some chemotherapy drugs, such as doxorubicin, cross into cells. As a result, less of the drug gets into the cancer cells[5].
4. Normal cells shelter cancer cells. When cancer cells attach to the matrix, they can become harder to kill with drugs. This is called cell adhesion-mediated drug resistance[5]. Cancer-associated fibroblasts also release growth signals and other messages that help cancer cells survive treatment[5].
5. The immune attack is switched off. Immune cells that calm the immune response, such as helper macrophages, make immunotherapy less effective[5]. Lactate from cancer cells also weakens killer T cells and natural killer cells[4],[5].
Treatment can also change the surroundings. For example, some chemotherapy drugs can cause cancer-associated fibroblasts to release signals that protect nearby cancer cells[5]. In addition, leftover cancer cells can rest quietly in protected spots in the body after treatment. That topic is covered in Why Can Cancer Return Years After Treatment?
Does the Tumor Microenvironment Change as Cancer Grows?
Yes. The tumor microenvironment changes all the time as the cancer grows, spreads and is treated[1],[5].
- At the start, a very small tumor can get oxygen and food from nearby blood vessels. Once it reaches about 1 to 2 cubic millimeters, parts of it become low in oxygen and acidic, and the tumor starts calling for new blood vessels[1].
- As the tumor grows, blood flow and the shape of the blood vessels can change from place to place and over time[5]. Fibroblasts can keep laying down matrix, and in some tumors this makes the tissue dense and stiff[2].
- Immune cells change roles. Some immune cells, such as macrophages and neutrophils, can switch from fighting the tumor to helping it as the cancer progresses[1].
- Treatment reshapes it. Chemotherapy, radiation and other treatments change the surroundings, sometimes in ways that help surviving cancer cells[5].
- New sites get their own surroundings. When cancer spreads, the cancer cells meet a new environment in the new organ. The tumor can prepare these places before cancer cells arrive[2].
The surroundings also differ with the type of tissue, the stage of the cancer and the treatment used[5]. Because the tumor microenvironment keeps changing, a treatment that works on it at one stage may work less well at another.
Can Treatments Target the Tumor Microenvironment?
Yes. Some treatments that target the tumor microenvironment are already in use, and many more are being tested[1],[5]. Instead of attacking only the cancer cells, these treatments try to take away the support that the surroundings provide.
Treatments already in use:
- Anti-angiogenesis drugs. These drugs block VEGF, a signal tumors use to grow new blood vessels. One example is bevacizumab[1]. When these drugs are used alone, many people do not respond, or the drugs stop working over time[1].
- Immune checkpoint inhibitors. These drugs release brakes on T cells so they can attack cancer cells inside the tumor's surroundings. They can work well for some people, but they help only a minority of patients[1]. How they work is explained in How Do Cancer Cells Hide from the Immune System?
- Combinations. Combining an anti-angiogenesis drug with an immune checkpoint inhibitor has shown success in some cancers[1].
Treatments being studied:
- Targeting cancer-associated fibroblasts. Drugs that target these fibroblasts, or block the TGF-beta signal that switches them on, are being tested[5].
- Changing macrophages. Researchers are testing drugs that reduce the number of helper macrophages or switch them back to a type that fights cancer[2].
- Breaking down the matrix. Loosening the dense mesh could help drugs get in, but results in advanced cancers have so far been limited[5].
- Targeting low oxygen. These include drugs that become active only in low-oxygen areas, drugs that block HIF, and approaches that improve blood flow and oxygen levels[3].
- Targeting acid and lactate. Drugs that block how cancer cells make or move lactate are being explored, but most are still at an early stage[4].
Many of these ideas have worked in the laboratory but still need to be proven in clinical trials[5].
Learning how the tumor microenvironment protects cancer does not mean that standard treatments are not worth having. Surgery, chemotherapy, radiation therapy, targeted drugs and immunotherapy help many people with cancer, and many are cured. Understanding the surroundings of a tumor helps researchers find ways to make these treatments work better, often by combining them with treatments that weaken the tumor's support.
Frequently Asked Questions
What is the difference between the tumor microenvironment and the tumor stroma? The tumor stroma is the supporting tissue of a tumor, made up of normal cells such as fibroblasts, blood vessel cells and immune cells, along with the protein mesh between them[2]. The tumor microenvironment is a broader term. It includes the stroma, but also the chemical signals and the living conditions, such as oxygen and acid levels, that surround the cancer cells.
Can the tumor microenvironment fight cancer as well as help it? Yes. Some parts of the tumor microenvironment work against cancer. Killer T cells can destroy cancer cells, and some immune cells can support an attack on the tumor[1]. Some types of cancer-associated fibroblasts may also hold a tumor back[2]. Cancer grows when the balance tips toward the cells and conditions that help it.
Is the tumor microenvironment the same in every cancer? No. The tumor microenvironment differs between types of cancer, between people and even between parts of the same tumor. For example, pancreatic cancer often has a very dense, fibrous environment, while breast tumors can sit among many fat cells[1]. These differences are one reason the same treatment can work well in one cancer and poorly in another.
What are "hot" and "cold" tumors? "Hot" and "cold" are informal terms that describe how many immune cells, especially T cells, are found inside a tumor. Hot tumors contain many T cells and tend to respond better to immunotherapy. Cold tumors contain few T cells, often because their surroundings keep immune cells out or switch them off. Researchers are testing ways to turn cold tumors into hot ones so that more people can benefit from immunotherapy.
Do blood cancers have a tumor microenvironment? Yes. Blood cancers such as leukemia, lymphoma and myeloma do not usually form a single solid lump, but the cancer cells still depend on their surroundings. They live in places such as the bone marrow and lymph nodes, where normal support cells and signals can help them grow and survive treatment.
Morais C. What Is the Tumor Microenvironment and How Does It Help Cancer Grow? [Internet]. BiologyWithin.com; 2026 Oct 18. Available from: https://www.biologywithin.com/2026/10/tumor-microenvironment-how-it-helps-cancer-grow.html
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