Immunotherapy has changed cancer treatment more than any other development of the past two decades. Instead of attacking tumors directly, as chemotherapy and radiation do, it helps the body’s own immune system find and destroy cancer cells. For some people with advanced cancers that were once quickly fatal, it has produced remissions lasting years. It does not work for everyone, and its side effects are different from those of other treatments. This guide explains the basics.

Why cancer escapes the immune system

The immune system’s T cells constantly patrol the body and can kill abnormal cells. Cancers survive by hiding from them or switching them off. One of their main tricks is to exploit checkpoints, natural “brakes” that stop T cells from attacking healthy tissue. Tumors display proteins that press those brakes, telling T cells to stand down. The discovery of how to release them earned James Allison and Tasuku Honjo the 2018 Nobel Prize in Medicine.

Checkpoint inhibitors: the most common type

Checkpoint inhibitors are antibodies, given by infusion or, increasingly, by injection under the skin, that block those brakes so T cells can attack. Most target a checkpoint called PD-1 or its partner PD-L1. They include Keytruda (pembrolizumab), Opdivo (nivolumab), Libtayo, Tecentriq (atezolizumab) and Imfinzi. Yervoy (ipilimumab) blocks a different brake, CTLA-4. These drugs are now used in more than a dozen cancers, alone or with chemotherapy, and increasingly before or after surgery in earlier-stage disease.

Other types of immunotherapy

  • CAR-T cell therapy engineers a patient’s own T cells to hunt a specific target. It is used in certain blood cancers (see our CAR-T explainer).
  • Bispecific antibodies (T-cell engagers) physically link T cells to cancer cells. They are approved for some lymphomas, leukemias, myeloma and one form of lung cancer.
  • TIL therapy grows immune cells taken from a patient’s own tumor in the lab and returns them in large numbers; it is approved for advanced melanoma.
  • Cancer vaccines aim to train the immune system against tumor markers. Personalized mRNA vaccines are in late-stage trials, with mixed results across the field so far.
  • Oncolytic viruses and immune-signaling drugs are used in a few specific situations.

Which cancers respond

Checkpoint inhibitors work best in cancers with many mutations, which make tumors look more foreign. They are standard treatments in melanoma, lung, kidney, bladder, head and neck, and liver cancers, Hodgkin lymphoma, and several others. They are much less effective in most cancers of the pancreas, prostate and ovary, and in most colorectal cancers — with an important exception for tumors that have a DNA-repair defect called dMMR or MSI-high, which respond very well (as in a recent approval in colon cancer).

Who is likely to benefit

Doctors use biomarker tests on tumor tissue to help predict benefit. The main ones are PD-L1 levels, MSI/dMMR status and tumor mutational burden. None is perfect: some people with “unfavorable” results respond, and some with favorable ones do not. Overall, depending on the cancer, a minority to about half of patients respond. The distinctive feature of immunotherapy is that when it works, the benefit can be long-lasting, sometimes continuing for years after treatment stops.

Side effects: different from chemotherapy

Immunotherapy does not usually cause hair loss or severe nausea. Its side effects come from an over-active immune system attacking healthy organs, and are called immune-related adverse events. The most common involve:

  • Skin: rash and itching;
  • Bowel: diarrhea and abdominal pain (colitis);
  • Lungs: new cough or breathlessness (pneumonitis);
  • Liver: usually detected on blood tests;
  • Hormone glands: thyroid, pituitary or adrenal problems, and rarely sudden type 1 diabetes;
  • Joints and muscles: pain and stiffness;
  • Rarely, the heart or nerves, which can be serious.

Most are mild and treatable, typically by pausing treatment and giving steroids. Some, particularly hormone problems, can be permanent and require lifelong replacement tablets.

Immunotherapy for lung cancer: what to watch

Lung cancer is one of the most common uses, and pneumonitis, inflammation of the lungs, deserves particular attention because its symptoms — cough, shortness of breath, chest discomfort — can be mistaken for the cancer itself or a chest infection. It is more likely in people who have also had chest radiation or who have existing lung disease. Caught early, it usually responds well to steroids, so new or worsening breathing symptoms should be reported promptly, not left until the next appointment.

The most important thing to know about timing

Side effects can appear weeks or months after starting treatment, and occasionally after it has finished. Patients are usually given a card or contact number and asked to report new symptoms early: persistent diarrhea, breathlessness, severe fatigue, headaches, dizziness, extreme thirst or a widespread rash. It is also important to tell any doctor or emergency department that you are, or have been, on immunotherapy, because the right treatment is often steroids, not antibiotics.

How treatment is given, and what it costs

Checkpoint inhibitors are typically given every three to six weeks, often for up to two years in advanced disease or one year around surgery. Scans can be confusing early on; occasionally tumors appear to enlarge before shrinking as immune cells move in. These drugs are expensive, with US list prices commonly in the range of $150,000 or more per year. Insurance and Medicare cover approved uses, though out-of-pocket costs vary, and hospital financial counselors and manufacturer programs can often help.

Questions to ask your oncologist

  • Has my tumor been tested for PD-L1, MSI/dMMR and other markers?
  • What is the chance of benefit in my situation, and how will we know if it is working?
  • Which side effects should I report straight away, and who do I call out of hours?
  • Do my other conditions, such as an autoimmune disease or a transplant, change the risks?

Immunotherapy is not a cure-all, and combinations that try to extend its benefit to more patients do not always succeed. But for the right patient it can be transformative. This explainer is general information, not medical advice.