Before starting cancer immunotherapy, your oncology team may recommend tests that look for specific features of the tumour. These are called biomarker tests. They can provide information about how a cancer behaves and whether certain immunotherapy approaches may be appropriate.
Biomarker testing is an important part of modern cancer treatment, but it is not a simple test that gives a yes-or-no answer about whether immunotherapy will work. Different cancers use different biomarkers, and the relevance of a particular result depends on the cancer type, stage, treatment history and the immunotherapy being considered.
If you are exploring how these tests fit into the wider treatment process, our Cancer Immunotherapy guide provides an overview of immunotherapy and the different ways it may be used in cancer care.
What Is Biomarker Testing?
A biomarker is a measurable feature of a cancer that can provide information about the disease or help guide treatment. Biomarkers may include proteins, gene changes, DNA characteristics or other molecular features found in tumour cells.
*AI-generated image - for illustration only. Clinical accuracy is not guaranteed.
For immunotherapy, some biomarkers can help identify cancers that may be more likely to respond to particular immune-based treatments. Other biomarkers may help doctors identify a different treatment altogether.
This is part of precision medicine, where treatment decisions are informed not only by where the cancer started and how far it has spread, but also by important biological characteristics of the tumour.
Why Is Biomarker Testing Important Before Immunotherapy?
Immunotherapy does not work in exactly the same way for every cancer. Two people with the same type of cancer can have tumours with very different biological characteristics, and those differences can influence treatment response.
Biomarker testing can help doctors answer questions such as:
- Does the tumour have a biomarker associated with a particular immunotherapy?
- Could another treatment, such as targeted therapy, be more appropriate?
- Is there information that may help estimate the likelihood of response?
- Are there treatment options that may be considered because of a specific molecular feature?
However, biomarker testing does not guarantee that immunotherapy will work. A favourable biomarker result can increase the likelihood of benefit in some situations, but it cannot predict an individual response with certainty.
Which Biomarkers Are Important for Immunotherapy?
There is no single universal biomarker used for every cancer. Some of the most important biomarkers associated with immune checkpoint inhibitor treatment include PD-L1, microsatellite instability (MSI), mismatch repair deficiency (dMMR) and, in selected situations, tumour mutational burden (TMB).
PD-L1
PD-L1 is a protein that can be present on cancer cells and certain immune cells around a tumour. It is involved in the PD-1/PD-L1 pathway, which can reduce immune activity against cancer.
Some immune checkpoint inhibitors target this pathway. Testing the amount of PD-L1 in a tumour can therefore help guide treatment decisions for several types of cancer.
PD-L1 results are usually obtained through immunohistochemistry (IHC), a laboratory technique that uses antibodies to identify proteins in tissue.
Microsatellite Instability and Mismatch Repair Deficiency
MSI describes changes in short, repeated sections of DNA called microsatellites. Mismatch repair (MMR) is a system that normally helps correct certain DNA errors.
When the mismatch repair system is deficient, described as dMMR, the tumour may accumulate many genetic changes. Tumours with MSI-high (MSI-H) or dMMR characteristics can be particularly relevant when considering certain immune checkpoint inhibitors.
These biomarkers are important across several cancer types and, in some treatment settings, can identify patients who may be eligible for immunotherapy based on the molecular characteristics of the tumour rather than solely on where the cancer began.
Tumour Mutational Burden
Tumour mutational burden (TMB) refers to the number of mutations found in the DNA of cancer cells, usually expressed as mutations per megabase.
A high TMB can sometimes indicate that a tumour contains many abnormal proteins that the immune system may recognise as different from healthy cells. This has made TMB an area of interest when predicting response to immune checkpoint inhibitors.
However, TMB is not a perfect predictor. A high TMB does not guarantee that immunotherapy will work, and a lower TMB does not necessarily mean that a patient cannot benefit from immunotherapy.
Is PD-L1 Testing the Same as Biomarker Testing?
No. PD-L1 testing is one type of biomarker testing. When people hear the term biomarker testing in relation to immunotherapy, they may assume it means checking PD-L1 alone. In reality, the appropriate testing depends on the cancer and treatment being considered.
For example, one patient may need PD-L1 testing, while another may require testing for MSI or MMR status. Some patients may also need broader molecular profiling to identify genetic changes that could affect treatment choices.
*AI-generated image - for illustration only. Clinical accuracy is not guaranteed.
This is why the biomarker testing process should be considered in the context of the individual cancer rather than as a standard checklist that applies to everyone.
What Sample Is Used for Biomarker Testing?
*AI-generated image - for illustration only. Clinical accuracy is not guaranteed.
Many biomarker tests are performed using a sample of the tumour obtained during a biopsy or surgery. The laboratory examines the tissue for specific proteins, genetic changes or other characteristics.
Depending on the cancer and the test, a blood sample may also be used. Blood-based testing, sometimes called a liquid biopsy, looks for cancer-related material circulating in the blood.
A blood-based test can be useful in selected situations, but it does not always replace tissue testing. Whether tissue, blood, or both are appropriate depends on the cancer, the biomarker being assessed and the clinical circumstances.
What Happens If There Is Not Enough Tumour Tissue?
Sometimes the original biopsy contains too little tissue for all the tests that may be needed. This can happen when the tumour sample is small or when several different analyses are required.
In such situations, the oncology team may consider whether another tissue sample is appropriate or whether a blood-based test could provide useful information. The decision depends on the cancer and the specific information needed.
A test result should always be interpreted in context. A negative result from a particular sample does not necessarily mean that the entire cancer lacks every potentially relevant biomarker.
How Are Biomarker Results Reported?
The format depends on the test. Results may be reported using terms such as:
- PD-L1 positive or negative
- PD-L1 percentage or score
- MSI-high or microsatellite stable
- dMMR or proficient mismatch repair
- TMB-high or a numerical TMB value
- Specific gene mutation, amplification or fusion
Some tests also provide a broader list of genetic alterations detected in the tumour. Not every finding on a molecular report has a treatment available, and not every alteration is relevant to immunotherapy.
Does a Positive Biomarker Mean Immunotherapy Will Work?
No. This is one of the most important points to understand about biomarker testing. A biomarker can indicate that a cancer has characteristics associated with a higher likelihood of responding to a particular treatment, but it cannot guarantee an individual response.
Cancer is biologically complex. Even when a tumour has a biomarker associated with immunotherapy response, other features of the tumour and immune system can influence whether the treatment works and how long the benefit lasts.
Similarly, the absence of one biomarker does not necessarily mean that all immunotherapy options are ruled out. Different treatments use different biomarkers, and some immunotherapy regimens may be appropriate without a particular biomarker being present.
Can Biomarker Results Change Over Time?
They can. Cancer cells can change as the disease develops or after treatment. A tumour's molecular characteristics may therefore differ from those found in an earlier biopsy.
*AI-generated image - for illustration only. Clinical accuracy is not guaranteed.
This is one reason why doctors may sometimes recommend additional testing when cancer returns or progresses. A new tissue sample or another type of molecular assessment may provide information that was not available from the original tumour.
However, repeat testing is not necessary in every situation. The decision depends on the cancer, previous testing, treatment history and the information needed to guide the next treatment.
What Is the Difference Between Biomarker Testing and Genetic Testing for Inherited Cancer Risk?
These tests are related to genetics but answer different questions. Biomarker testing for treatment usually looks for changes acquired by the cancer cells during a person's lifetime. These changes can help guide treatment decisions.
Inherited or germline genetic testing looks for genetic changes that a person was born with and that may increase the risk of developing certain cancers. These findings can also have implications for family members.
A tumour biomarker result does not automatically mean that a genetic change was inherited. If an inherited cancer risk is suspected, a separate assessment may be recommended.
The Bottom Line
Biomarker testing can provide valuable information before cancer immunotherapy by showing whether a tumour has biological features that may influence treatment choices. Depending on the cancer, testing may include PD-L1, MSI, MMR status, TMB or broader molecular profiling.
However, biomarkers are not crystal balls. A result that is associated with immunotherapy response does not guarantee that treatment will work, and the absence of one biomarker does not necessarily rule out all immunotherapy options.
The most useful way to understand a biomarker report is to look at it alongside the cancer type, stage, pathology, previous treatments and the available treatment options. Together, these factors provide a more complete picture of whether immunotherapy may have a role in your care.
