Cancer immunotherapy: how it works, who it helps and its risks

Today, cancer immunotherapy most often means checkpoint inhibitors: drugs that take the “brakes” off the immune system so that it attacks the tumor itself. It is not suitable for everyone: the decision depends on the tumor type, the stage and sometimes biomarkers. The most important thing for patients to know is that the side effects are different from chemotherapy and can appear at any time, including after treatment has ended.

How checkpoint inhibitors work

The immune system has “off switches” called checkpoints. They exist to stop the immune system from attacking the body’s own tissues. Tumors have learned to exploit them.

• PD-1 is a protein on T cells (a type of immune cell). When it binds to PD-L1 on a tumor cell, the T cell gets a “don’t attack” signal. PD-1 and PD-L1 inhibitors block this connection.
• CTLA-4 is another “off switch” on T cells; it works at an earlier stage of the immune response. CTLA-4 inhibitors are usually used in combination with PD-1 or PD-L1 inhibitors.

The drugs themselves don’t kill tumor cells — they help the immune system find and attack them. Most are given as an intravenous drip; some are also available as an injection under the skin.

Immunotherapy may be given on its own, together with chemotherapy, or before or after surgery, depending on the diagnosis. I explained how treatment cycles are organized in my article on what chemotherapy is like: immunotherapy follows a similar logic.

Who immunotherapy is for, and what biomarkers are

The indications depend on tumor type and stage. For some tumors, immunotherapy has become part of standard treatment; for others, it has not yet shown a benefit. Biomarkers are used to pin down who is more likely to benefit.

That last figure is telling: even with a “matching” biomarker, far from everyone responds. A biomarker raises the likelihood of benefit but does not guarantee it. And the reverse is also true: in some situations, immunotherapy is given without any biomarker because the benefit has been proven for the whole patient group.

All of these biomarkers are tested on tumor tissue — usually on the same paraffin blocks used to make the diagnosis. That is why it is important to keep your blocks and slides: they may be needed for new tests, sometimes years later. If you have had a molecular genetic test to select targeted therapy, MSI and TMB are sometimes assessed in the same test. For more about these tests, see my article on targeted therapy.

Immune-related side effects: what they are and why they are different

When we take the brakes off the immune system, there is a risk that it will attack not only the tumor but healthy organs too. These reactions are called immune-related adverse events. They can affect any organ, but most often the skin, bowel, lungs, liver and hormone-producing glands.

Most immune-related side effects are mild or moderate and reversible if they are spotted early and treated in time. They are usually treated with corticosteroids (steroid hormones), sometimes with other drugs that suppress the immune system; immunotherapy may be paused during this time.

What sets hormone-related side effects apart is that the gland’s function often does not recover. For example, if hypothyroidism (an underactive thyroid) develops, long-term hormone replacement is usually needed. This is not dangerous if the dose is adjusted in time — but you should know about it in advance.

With a combination of CTLA-4 and PD-1 inhibitors, side effects are more common than with a single drug.

That is why during immunotherapy your tests go beyond a blood count. Before each dose, doctors usually check liver tests, kidney function, thyroid hormones and glucose — your oncologist decides the exact list. Some immune complications, such as hepatitis or thyroid problems, show up first only in blood tests and are caught before symptoms appear.

Another type of reaction is an infusion reaction: during the drip you may get chills, fever, facial flushing, rash, itching, dizziness or wheezing. Tell the nurse straight away.

Why you should report any new symptom, even months later

Immune-related side effects most often appear in the first weeks to three months of treatment. But according to ESMO, they can also occur a few days after the first dose or a year after treatment has ended. The Russian Society of Clinical Oncology (RUSSCO) guidelines even describe delayed reactions — those that occur 12 months or more after immunotherapy has stopped.

If you have ever had immunotherapy, tell your doctor about it whenever you have a new symptom, even if treatment ended long ago. Diarrhea or a cough that looks harmless may turn out to be colitis or pneumonitis, which are treated differently from an infection.

I usually advise carrying a card or discharge summary that states which drug you received and when. This is especially important if you see a GP, go to the emergency department or see a doctor in another specialty.

Call your oncologist the same day if you have loose stools more often than usual, blood in your stool, new shortness of breath or cough, a severe headache, double vision, marked weakness or yellowing of the skin. Call your local emergency number (911 in the US, 999 in the UK, 112 in the EU) if you are short of breath at rest, have chest pain, confusion or fainting.

Why the response takes time, and what pseudoprogression is

Immunotherapy works indirectly: the immune system needs time to “switch on”. So the effect sometimes becomes visible later than with chemotherapy.

Occasionally there is pseudoprogression: on a follow-up CT scan the tumor looks bigger or new spots appear, and then on later scans everything shrinks. One explanation is that activated immune cells move into the tumor, and its volume temporarily increases. This is uncommon, so you cannot count on it by default: more often, a tumor growing on scans means the tumor really is growing.

How doctors tell the difference in practice: if the patient is stable or feeling better, the doctor may continue treatment and repeat the scan. The international criteria for assessing response to immunotherapy (iRECIST) recommend repeat imaging 4–8 weeks later to confirm progression. If the patient is getting worse or develops new symptoms, the approach is changed without waiting. The decision is always made by your oncologist. On choosing a monitoring method, see my article on PET-CT, CT and MRI.

Questions to ask your oncologist

• Why have I been prescribed immunotherapy — because of my diagnosis, my PD-L1 level or another biomarker?
• On its own or together with chemotherapy? How long is treatment planned for?
• Which tests should I have before each dose (liver, thyroid hormones and others)?
• Which symptoms need a same-day call, and to which number?
• When will my first follow-up CT be, and how will we tell pseudoprogression from progression?
• How long will I need follow-up after treatment ends?

If you are having immunotherapy and want help making sense of your test results, new symptoms or CT results, we can go through them in an online consultation — after our conversation I will send you a written summary.

Sources

1. Immune Checkpoint Inhibitors — American Cancer Society, accessed 2026
2. Immunotherapy Side Effects: Patient Guide — ESMO, 2017
3. Practical guidelines for the management of immune-related adverse events — RUSSCO, 2023
4. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication — U.S. FDA, 2017
5. FDA approves pembrolizumab for adults and children with TMB-H solid tumors — U.S. FDA, 2020
6. iRECIST — RECIST Working Group / EORTC, 2017