Immunotherapy: helping your own immune system work against the Cancer

Cancer immunotherapy uses or redirects the immune system to recognise and attack Cancer. The most widely used form in solid tumours is immune checkpoint inhibition. Other forms include cellular therapies such as CAR T-cell therapy, bispecific antibodies and certain monoclonal antibodies, particularly in blood Cancers.

How immunotherapy works

T cells are immune cells that can recognise abnormal proteins and help eliminate abnormal cells. Cancer cells can develop ways to avoid this immune response. One important mechanism is the use of immune “checkpoints” — normal control pathways that prevent excessive immune activation. Some Cancers exploit these pathways to switch off an anti-Cancer immune response.

• PD-1/PD-L1 pathway — PD-L1 on tumour or immune cells can bind PD-1 on T cells and reduce immune activity.
• CTLA-4 pathway — another immune checkpoint that helps regulate T-cell activation.
• LAG-3 and other checkpoints — additional immune pathways now treatment targets in selected Cancers.

Checkpoint inhibitors: releasing the brakes

Checkpoint inhibitors block these inhibitory signals. Drugs such as pembrolizumab and nivolumab block PD-1; other medicines target PD-L1, CTLA-4 or LAG-3. Depending on the Cancer, they may be used alone or combined with chemotherapy, another immunotherapy, an antibody-drug conjugate, targeted treatment, radiation or surgery — these combinations are Cancer-specific and should not be assumed to be interchangeable.

Cancers where immunotherapy has made an important difference

Immunotherapy has had a major impact in selected settings across a number of Cancers. The benefit can range from improving cure rates in early-stage disease to producing durable long-term disease control in some people with advanced Cancer.

This does not mean every patient with one of these Cancers should receive immunotherapy. The indication depends on stage, biomarker profile, previous treatment, coexisting illnesses, potential toxicity and regulatory availability.

Immunotherapy is only one part of precision oncology: targeted therapy can be equally important

Before deciding on immunotherapy, it is often essential to ask whether the Cancer has a target that can be treated more specifically. Biomarker testing can identify gene changes, proteins or other tumour features that predict benefit from targeted therapy, immunotherapy or both. The right test depends on the Cancer; broad genomic testing is not automatically necessary for every patient. A high PD-L1 result does not automatically override an actionable driver mutation. Treatment sequencing matters.

• Lung Cancer — molecular testing can identify actionable alterations such as EGFR, ALK, ROS1, BRAF, MET exon 14, RET, NTRK, KRAS G12C and selected HER2 alterations. In advanced NSCLC with certain driver alterations, targeted therapy is usually prioritised over single-agent immunotherapy, even when PD-L1 is high.
• Breast Cancer — ER/PR and HER2 remain fundamental treatment biomarkers. In appropriate settings, additional testing such as PIK3CA, ESR1, germline BRCA1/2/PALB2 and HER2-low/ultralow assessment can influence systemic therapy choices.
• Colorectal Cancer — RAS, BRAF, HER2 and MMR/MSI testing can direct targeted therapy or immunotherapy and should be interpreted in the clinical context.
• Across Cancers — selected alterations such as NTRK fusions and other validated targets can occasionally direct tumour-agnostic targeted therapy.

This is why I prefer to discuss the complete tumour profile rather than label a treatment as simply “chemo”, “immunotherapy” or “targeted therapy”. The best plan often comes from matching the biology of the Cancer with the evidence, the stage of disease and the priorities of the person receiving treatment. See Targeted Therapy & Molecular Testing for more on how testing guides this choice.

Who may benefit from checkpoint immunotherapy?

There is no single universal test. Depending on the Cancer, one or more of the following may be relevant:

• PD-L1 expression — useful in several Cancers, but not a perfect predictor. Some low-PD-L1 tumours respond and some high-PD-L1 tumours do not.
• Mismatch repair (MMR) / microsatellite instability (MSI) — dMMR or MSI-H status can strongly predict benefit from checkpoint inhibition in several tumour types.
• Tumour mutational burden (TMB) — can be useful in selected settings, but its role varies by tumour type and it should not be interpreted in isolation.
• Histology and stage — the same biomarker may have different implications in different Cancers or stages.
• Actionable molecular drivers — especially important in lung Cancer.
• Patient factors — autoimmune disease, organ transplant, baseline organ function, performance status, infection risk and previous treatment can affect safety and choice of therapy.

Why MSI / mismatch-repair testing deserves special attention

Mismatch-repair deficiency causes tumours to accumulate large numbers of DNA errors. These tumours often generate more abnormal proteins that the immune system can recognise. For this reason, MSI-H/dMMR status can identify Cancers that are particularly sensitive to immune checkpoint blockade. Testing is especially relevant in colorectal and endometrial Cancers and can also be important in gastric and several other solid tumours. MMR/MSI results may also raise the question of an inherited Cancer syndrome such as Lynch syndrome, in which case germline genetic assessment may be appropriate.

Side effects are different from chemotherapy, not necessarily absent

Because checkpoint inhibitors activate immune responses, they can sometimes cause the immune system to inflame normal organs — called immune-related adverse events. Most are manageable when recognised early, but some can become serious. Common or important examples include rash or itching, thyroid dysfunction, diarrhoea or colitis, hepatitis, pneumonitis and inflammation of endocrine glands. Less common but potentially serious toxicities include myocarditis, nephritis, severe neurologic complications and new-onset insulin-dependent diabetes.

Side effects may occur during treatment or sometimes after treatment has stopped. New symptoms should be reported promptly rather than waiting for the next review. Management depends on the organ involved and severity: treatment may need to be paused, and corticosteroids or other immunosuppressive medicines may be required.

How immunotherapy may be combined with other treatments

• With chemotherapy — standard in several Cancers, including many lung Cancer regimens and selected breast, gastric and cervical settings.
• With another checkpoint inhibitor — used in selected diseases such as melanoma and renal cell carcinoma, with a different toxicity profile.
• With targeted therapy or antibody-drug conjugates — useful in specific evidence-based combinations, not a routine strategy for every targetable mutation.
• Around surgery — increasingly used before and/or after surgery in selected lung, breast, melanoma and other Cancers.
• With radiation — sometimes used in defined clinical situations depending on tumour type and treatment intent.

How response is monitored, and for how long

Response is usually assessed using symptoms, examination, laboratory tests and scheduled imaging. Rarely, immune-related patterns of response can look different from conventional treatment responses, so an early scan change is interpreted together with the clinical picture rather than in isolation. There is no single duration for all immunotherapies: some regimens are given for a defined number of cycles or approximately one to two years, others continue until progression or unacceptable toxicity. The duration depends on the Cancer, treatment setting, drug, response and the evidence supporting that regimen.

Circulating tumour DNA (ctDNA) is an important and rapidly evolving tool in oncology, but its use for routine monitoring during immunotherapy is Cancer- and setting-specific. It should not replace standard clinical assessment or imaging unless supported by evidence for that particular situation.

When should you ask about immunotherapy?

If you have been diagnosed with Cancer, useful questions to discuss with your oncology team include:

• Is immunotherapy established for my Cancer and stage?
• Do I need PD-L1, MMR/MSI or other biomarker testing?
• Does my Cancer need molecular testing for a targeted treatment before we choose immunotherapy?
• What is the expected benefit in my specific situation?
• What immune-related side effects should I report urgently?
• How long is treatment planned and how will we assess response?

Immunotherapy in the Indian context

Immunotherapy can be expensive, and access varies. A sound treatment decision should consider not only whether a drug can work, but also the magnitude of expected benefit, duration of therapy, toxicity monitoring, total treatment cost and whether another evidence-based option may provide similar or better value for that individual. When immunotherapy is appropriate, patient-assistance pathways or lower-cost approved options may sometimes help, depending on the medicine and treatment centre.

My approach

I combine tumour biology with the person in front of me. A treatment decision is not made from a biomarker report alone — I consider the type and stage of Cancer, molecular and pathology results, expected benefit, side effects, other medical conditions, day-to-day function, practical feasibility and your own priorities. Every treatment should have a reason. If I recommend immunotherapy, I want you to understand why it is being chosen, whether another option such as targeted therapy is relevant, what benefit we are aiming for, what side effects to watch for, and how we will know whether the treatment is working.

This page is general information, not medical advice for your situation, and does not promote or endorse any specific medicine or brand. The suitability, choice and combination of any immunotherapy depends on a full clinical assessment. Medically reviewed by Dr Sneha Kommineni.