If you have just been told that immunotherapy is part of your plan — or you are reading the word “Keytruda” on a pharmacy printout at midnight and trying to understand what you are about to go through — I want to slow this down for you. Immunotherapy is genuinely different from chemotherapy. It works differently, it can succeed in ways chemotherapy cannot, and its side effects follow their own rules. My aim here is to explain it clearly, honestly, and completely, so that you walk into your next appointment knowing what to ask and what to watch for.
What immunotherapy actually is
Your immune system already knows how to kill abnormal cells. Every day, specialised white blood cells called T cells patrol your body looking for anything that does not belong. The problem with cancer is that tumours learn to hide. They flip switches that tell the immune system to stand down, so your T cells drift past the danger without attacking.
The most widely used form of immunotherapy — the kind this article focuses on — is a group of drugs called checkpoint inhibitors. To understand them, picture your T cells as having built-in brakes. These “checkpoints” exist for a good reason: they stop your immune system from attacking your own healthy tissue and keep it from over-reacting once a threat has passed. But cancer exploits those same brakes to protect itself. Checkpoint inhibitors release the brakes, so your own T cells are freed to recognise and destroy the cancer.
This is worth pausing on, because it changes everything about how the treatment behaves. The drug does not attack the cancer directly. Your immune system does the work. The medicine simply removes the obstacle in the way.
Chemotherapy is a poison aimed at fast-dividing cells. Immunotherapy is a key that unlocks your own defences. That single difference explains most of what follows — why it can produce long-lasting responses, why the side effects look so different, and why “is it working?” is a harder question to answer.
How it works: PD-1, PD-L1, and CTLA-4 in plain words
You will hear a handful of technical names. Let me define them once, simply, so they stop being intimidating.
- PD-1 is a brake on the surface of the T cell. Its full name is “programmed death-1,” which sounds alarming but only describes the receptor’s role as an off-switch. It has nothing to do with your prognosis.
- PD-L1 is the matching signal, often displayed by cancer cells (and some normal cells). When PD-L1 presses on PD-1, the T cell shuts down. Many tumours coat themselves in PD-L1 precisely to do this — it is one of the ways they stay invisible.
- CTLA-4 is a different brake, one that acts earlier, when T cells are first being switched on in the lymph nodes. Releasing it broadens the immune response, which is powerful but also more likely to spill over onto healthy tissue.
Checkpoint-inhibitor drugs are sorted by which brake they release:
- Anti-PD-1 drugs — pembrolizumab (Keytruda) and nivolumab (Opdivo) are the best known, with several others now approved such as cemiplimab and dostarlimab. They block the PD-1 brake on the T cell.
- Anti-PD-L1 drugs — such as atezolizumab, durvalumab, and avelumab. They block the PD-L1 signal on the cancer’s side. In practice, anti-PD-1 and anti-PD-L1 drugs work on the same pathway from opposite ends.
- Anti-CTLA-4 drugs — ipilimumab (Yervoy) is the main one, with tremelimumab also in use. It releases the earlier brake.
Sometimes two are combined — for example an anti-PD-1 drug with an anti-CTLA-4 drug. Combinations can be more effective for certain cancers, but they also carry a higher chance of the immune-related side effects I describe below. This is one of the real trade-offs your oncologist weighs for you specifically: more immune firepower, but a greater risk of the immune system turning on healthy organs.
These are not the only kinds of immunotherapy in existence. There are also CAR T-cell therapies (where your own T cells are removed and re-engineered in a lab, used mainly in some blood cancers such as certain lymphomas, leukaemias, and myeloma), bispecific antibodies, cancer vaccines, oncolytic viruses, and cytokines like interleukin-2. Those are separate topics with their own rules. When most people with a solid tumour today say “immunotherapy,” they usually mean the checkpoint inhibitors, so that is what I will keep to.
Who immunotherapy helps — and who it doesn’t
This is the part I most want you to hear clearly, because both false hope and false despair do harm here. Checkpoint inhibitors help a subset of patients. When they work, the response can be remarkably durable — some people see their cancer controlled for years, longer than we would ever have expected from older treatments, and a minority appear to have very long-term control. But they do not work for everyone, and we cannot yet promise in advance exactly who will be in the fortunate group. Honesty on both sides of that sentence matters.
Checkpoint inhibitors tend to work better in cancers that are more “visible” to the immune system — usually because those tumours carry many mutations that make them look foreign. These include:
- Melanoma (the skin cancer where much of this science was first proven, and where it transformed outcomes)
- Lung cancer (particularly non-small-cell lung cancer, and also small-cell in some settings)
- Kidney cancer
- Bladder and other urinary-tract cancers
- Head and neck cancers
- Certain cancers with a specific genetic feature called MSI-high or mismatch-repair-deficient (dMMR) — more on this below — which can occur across many organs, including bowel and womb cancers
- Some others, including Hodgkin lymphoma and certain liver, stomach, oesophageal, cervical, and triple-negative breast cancers
It is also used at different stages: sometimes for advanced or metastatic disease, sometimes after surgery to lower the chance of the cancer returning (called adjuvant treatment), and sometimes before surgery to shrink a tumour and prime the immune system (neoadjuvant treatment). Where it fits depends on your exact cancer, its stage, and its biomarkers, so treat the list above as a map of the territory, not a prediction about you. New approvals arrive steadily, so a cancer not listed here today may still be a candidate — your team has the current picture.
Biomarkers: the imperfect crystal ball
Because we cannot yet be certain who will respond, we use biomarkers — measurable clues from your tumour — to improve the odds of choosing well. You may see these on your pathology report, and it is completely reasonable to ask for them to be explained.
- PD-L1 expression is a score for how much PD-L1 the tumour displays. Higher levels often (not always) predict a better chance of benefit. It is usually reported as a percentage — a Tumour Proportion Score — or as a “Combined Positive Score” (CPS). The threshold that counts as “positive” differs by cancer type and by drug, which is why the same number can mean different things in different reports.
- MSI-high / dMMR (microsatellite instability / mismatch-repair deficiency) means the tumour has a faulty DNA-proofreading system. Such tumours accumulate many mutations, which tends to make them more visible to the immune system — and often more responsive to checkpoint inhibitors, wherever in the body they arise. This is one of the strongest predictors we have.
- TMB (tumour mutational burden) counts how many mutations a tumour carries overall. A high burden can signal better odds of response, because more mutations mean more flags for the immune system to spot.
I want to be candid: these biomarkers are helpful but imperfect. Some people with low PD-L1 respond well; some with high PD-L1 do not. The tests guide the decision; they do not decide it on their own. If your team recommends immunotherapy despite a modest PD-L1 score, or holds back despite a high one, there is usually good reasoning behind it — the type of cancer, the stage, your other health conditions, and what else is available all feed into the choice. It is entirely fair to ask them to walk you through that reasoning until it makes sense to you.
How it is given, and what to expect
Most checkpoint inhibitors are given as a drip into a vein (an infusion), usually every two, three, four, or six weeks depending on the drug and dose. A few are now available as an injection under the skin. The infusion itself is often quick — commonly around 30 to 60 minutes — and you sit in a chair while it runs. There is no drip of the harsh, hair-losing chemotherapy many people picture. You will typically have blood tests before each cycle, and scans at intervals to assess how things are going.
Practical things worth knowing before your first cycle:
- Many people feel largely normal on treatment days. Fatigue is the most common general effect, and it can build over time. Most people continue working, driving, and living ordinary life, adjusting the pace as needed.
- You will usually be given a patient alert card or wallet card. Carry it always. If you ever need emergency care, it tells any doctor you are on immunotherapy — which changes how they interpret certain symptoms.
- Tell your team about every medicine and supplement you take, and about any autoimmune condition (such as rheumatoid arthritis, lupus, inflammatory bowel disease, psoriasis, or thyroid disease) or any previous organ transplant. These genuinely matter for your safety: immunotherapy can flare an existing autoimmune condition, and in transplant recipients it can, rarely, trigger rejection. None of these is automatically a barrier, but they change the calculation.
- Ask about vaccinations before starting. Inactivated vaccines (such as the usual flu and COVID vaccines) are generally considered safe and often encouraged, but live vaccines are usually avoided — your team will advise on timing.
- Treatment often continues for many months, sometimes up to a defined period such as two years, or until it stops helping or side effects require a pause. The plan is individual, and it can change as your scans come in.
The side effects that make immunotherapy different
Here is the most important safety section in this article, so please read it even if you skim the rest. Because these drugs unleash your immune system, the immune system can sometimes turn on healthy organs as well as the cancer. These are called immune-related adverse events, and they are genuinely different from chemotherapy side effects. They are not “the drug being toxic” in the ordinary sense — they are inflammation, your own defences over-firing in the wrong place.
Three features make them distinctive:
- They can affect almost any organ, because inflammation can land anywhere.
- They can appear at any time — not just during treatment, but weeks or even months in, and occasionally after you have stopped altogether.
- Caught early, most are very manageable, usually by pausing the drug and giving steroids (or, for the hormone glands, replacing the missing hormone) to calm things down. Caught late, some can become serious. Speed of reporting matters more than anything else.
The more common immune-related effects include:
- Colitis (inflamed bowel) — diarrhoea, more frequent or looser stools, blood or mucus, tummy pain or cramping. New or worsening diarrhoea is never something to just wait out on immunotherapy, and over-the-counter anti-diarrhoea remedies can mask a problem, so check first.
- Pneumonitis (inflamed lungs) — a new or worsening cough, breathlessness, or chest discomfort. This one can be serious and deserves prompt attention.
- Endocrine problems (inflamed hormone glands) — the thyroid is most often affected, causing tiredness, feeling cold and sluggish (underactive) or anxious, hot, and fast-heartbeat (overactive). The pituitary and adrenal glands can also be affected, and inflammation of the pancreas can rarely cause diabetes. Some of these, such as an underactive thyroid, an underactive pituitary, or diabetes, may be permanent and need lifelong hormone replacement — which is manageable, but worth knowing in advance.
- Skin — rash, itching, dryness, changes in skin colour (sometimes patchy pale areas). Usually mild, but severe skin reactions do rarely occur and need urgent review.
- Hepatitis (inflamed liver) — often picked up on blood tests before you feel anything; sometimes yellowing of the eyes or skin, dark urine, pale stools, or pain under the right ribs.
- Less commonly, inflammation of the kidneys, joints, muscles, heart, eyes, nerves, brain, or other glands. Heart and neurological inflammation are rare but can be serious, which is exactly why prompt reporting of anything new matters.
When to contact your team, and when it is an emergency
I cannot examine you, and this article is not a substitute for your own team — but I can tell you the principle every immunotherapy patient should hold onto:
On immunotherapy, do not “tough out” new symptoms. A symptom you would ignore on any ordinary week may be your immune system inflaming an organ. Report it early. Steroids given promptly usually settle these problems; delay is what turns a manageable event into a dangerous one.
Contact your oncology team promptly (use the 24-hour number they gave you) if you develop: diarrhoea or more frequent stools, a new cough or breathlessness, unusual or severe fatigue, yellowing of skin or eyes, a marked rash, new or persistent headaches, dizziness, vision changes, palpitations, muscle weakness, or extreme thirst and passing a lot of urine. You do not need to be certain it is related — that is exactly what they are there to judge.
Seek emergency care if you have: severe breathlessness or chest pain, severe or bloody diarrhoea, signs of serious dehydration, sudden confusion, fainting, or you simply feel dangerously unwell. When you arrive, tell them you are on immunotherapy and show your alert card — this is not a routine detail; it directly changes how they will investigate and treat you.
One more practical point: if you are prescribed steroids for a side effect, take them exactly as directed and do not stop suddenly, because stopping abruptly can cause its own problems. They are the tool that lets many people recover and, in many cases, continue treatment safely.
How we judge whether it is working — and pseudoprogression
People often ask me how they will “feel” it working. The honest answer is that you usually cannot tell from how you feel, and trying to read the tea leaves of your own symptoms will only add to your worry. Feeling well does not prove it is working; feeling tired does not prove it is failing. Response to immunotherapy is judged on scans and clinical assessment by your team, at planned intervals — typically the first check comes a couple of months in.
There is a further wrinkle unique to immunotherapy called pseudoprogression. Because the treatment works by flooding the tumour with immune cells, a scan taken early can occasionally show the tumour looking larger — not because the cancer has grown, but because it is swollen with the very immune cells attacking it. On a later scan, it shrinks. This is why your oncologist may not panic at one ambiguous scan and may recommend a repeat scan before drawing conclusions, and why doctors sometimes use immunotherapy-specific ways of reading scans. It is uncommon, but it is real, and it is one more reason to let the whole picture — scans over time, plus how you are doing — guide the judgement rather than a single frightening number.
The opposite pattern exists too, though rarely: a small number of people experience unusually rapid growth on treatment. This is another reason your team looks at the trajectory across several assessments rather than reacting to any one result in isolation.
If it works: durable responses and stopping treatment
One of the most hopeful features of checkpoint inhibitors is that, in the people who respond, the benefit can outlast the treatment. Unlike many drugs whose effect stops when you stop taking them, immunotherapy can leave your immune system with a kind of trained memory of the cancer. This is why some people can eventually come off treatment — often after a set period such as two years, or after a strong and sustained response — and stay well.
That said, stopping is an individual decision made with your team, weighing how deep and durable the response has been against the small risk of the cancer reawakening. If it does return, re-treatment is sometimes possible. I mention this not to promise you a particular outcome, but so that the idea of eventually finishing treatment feels like a real, discussable possibility rather than something you have to raise nervously on your own.
How immunotherapy differs from chemotherapy
Because so many people arrive here having pictured chemotherapy, let me set the two side by side.
- Target. Chemotherapy directly poisons fast-dividing cells, cancerous and healthy alike. Immunotherapy does not attack cells directly — it releases your immune system to do it.
- Side-effect pattern. Chemotherapy’s classic effects — hair loss, nausea, low blood counts, mouth sores — come from damage to fast-dividing healthy tissue. Immunotherapy usually does not cause those. Its signature effects are inflammation of organs, driven by an over-active immune response.
- Timing of side effects. Chemotherapy effects often follow a predictable rhythm within each cycle, easing between doses. Immune-related effects can appear at any point, including late and even after stopping.
- Shape of benefit. Chemotherapy responses often fade as the cancer adapts. Immunotherapy, when it works, can sometimes produce durable, long-lasting control — a genuinely different kind of hope, though not a guarantee and not for everyone.
- They are not rivals. Immunotherapy and chemotherapy are often deliberately combined, because chemotherapy can make a tumour more visible to the immune system. So do not think of it as choosing sides; for many cancers the modern standard is both together.
Common myths, gently corrected
- “Immunotherapy is natural, so it is gentle.” It uses your own immune system, but it is a powerful medicine that can cause serious inflammation. Gentle in some ways, not to be underestimated in others.
- “No side effects means it is not working.” False. Many people benefit with few or no immune-related effects. Side effects are not a scoreboard, and their presence or absence does not reliably predict response.
- “It works for every cancer now.” Not yet. It helps a subset, in particular cancer types, and research is steadily widening that circle — but it is not universal.
- “If chemo failed, immunotherapy won’t help.” They work by completely different routes, so a poor chemotherapy response tells us little about how immunotherapy will do.
- “I can boost it with supplements.” Please be cautious. Some supplements — and particularly steroids or immune-affecting drugs taken without your team’s knowledge — could interfere with how immunotherapy works. Always tell your team what you are taking before you start anything new.
Sensible questions to take to your team
Write these down before your appointment; it is hard to think clearly in the room, and a written list quietly gives you permission to ask.
- Which specific drug am I having, and is it given alone or combined with another immunotherapy or with chemotherapy?
- What is the goal — to shrink the cancer, to keep it controlled, or to lower the chance of it coming back after surgery?
- Were my tumour’s biomarkers (PD-L1, MSI/dMMR, TMB) tested, and what did they show?
- How often is the infusion, and how long do you expect me to stay on it?
- Which side effects should I watch for, and what is the exact number to call, day or night?
- When is my first assessment scan, and how will we handle an unclear result?
- Do any of my existing conditions, medicines, or past transplant change my risk?
- Which vaccinations are safe, and is there anything I should do before I start?
What to take from this
- Immunotherapy releases the brakes on your own immune system so it can attack the cancer — it does not poison the cancer directly the way chemotherapy does.
- Checkpoint inhibitors like Keytruda (pembrolizumab), Opdivo (nivolumab), and Yervoy (ipilimumab) target the PD-1, PD-L1, or CTLA-4 brakes.
- They help a subset of patients, often durably, and tend to work better in melanoma, lung, kidney, bladder, head-and-neck, and MSI-high/dMMR cancers.
- Biomarkers (PD-L1, MSI/dMMR, TMB) improve the odds of choosing well but are imperfect predictors — they guide the decision, they do not settle it alone.
- The side effects are immune-related inflammation — colitis, pneumonitis, thyroid and hormone problems, rash, hepatitis — and can appear late. Report new symptoms early; prompt steroids usually settle them.
- Whether it is working is judged on scans over time, not on how you feel, and early apparent growth can be harmless pseudoprogression.
- When it works, the benefit can be durable, and some people are eventually able to stop treatment and stay well.
Everything here is general education, not medical advice, and it cannot account for the particular details of your cancer and your health. Your own oncology team knows those details — take these questions and worries to them, carry your alert card, report new symptoms early, and let them be your guide.