Immunotherapy and chemotherapy are common cancer treatments. Doctors use both to treat many types of tumors. But the similarities don't go much further. The therapies target cancer in different ways. They also come with distinct side effects. Keep reading to understand the most important differences between chemotherapy and immunotherapy.
1: Immunotherapy & Chemotherapy Work Differently
The biggest difference between these therapies is the way they work. Chemo uses drugs that damage and kill fast-growing cells. Immunotherapy teaches a patient's own immune system to attack cancer.
How It Kills Cancer: Chemotherapy takes advantage of how quickly cancer cells copy themselves. These drugs hurt cells as they're copied. Some stick to and damage DNA. Others break the parts of the cell required for growing and dividing.
Types of Chemo:
- Alkylating agents
- Anti-cancer antibiotics
- Antimetabolites
- Corticosteroids
- Mitotic inhibitors
- Nitrosoureas
How It Kills Cancer: Immunotherapy uses different parts of the immune system to target cancer cells. Some drugs serve as a sort of label that tells regular immune cells to attack tumors. Others reprogram immune cells to find and eliminate cancerous tissues.
Types of Immunotherapy:
- Cancer vaccines
- CAR T-cell therapy
- Immune checkpoint inhibitors
- Monoclonal antibodies
- Oncolytic viruses
2: Immunotherapy & Chemo Have Distinct Side Effects
Chemo and immunotherapy both fight cancer but in different ways. Because of this, they have some side effects in common and others that are not.
- Bleeding
- Bruising
- Fertility problems
- Hair loss
- Low iron (anemia)
- Numbness
- Tingling
- Blood pressure changes
- Chills
- Dizzy episodes
- Fever
- Fluid retention (swelling)
- Headaches
- Muscle or joint pain
- Diarrhea
- Higher risk of infection
- Loss of appetite
- Mouth sores or ulcers
- Nausea
- Skin problems
- Tiredness
- Vomiting
Both treatments can cause serious complications. But some patients may find immunotherapy side effects more tolerable than those of chemo. For either treatment, you should report any adverse reactions to your care team. This can help providers manage them quickly and effectively.
3: Some Cancers Respond Better to Immunotherapy, Others to Chemo
Cell characteristics vary between types and even subtypes of cancerous tumors. Because of this, generally speaking, some respond best to chemotherapy and others to immunotherapy.
Mesothelioma cell types provide a good example of this. Immunotherapy is slightly more effective for epithelioid mesothelioma than chemotherapy. But it’s twice as effective as chemo for sarcomatoid and biphasic mesothelioma.
4: Immunotherapy Can Keep Working After Treatment
In general, chemo stops fighting cancer once it leaves the patient's body. But some immunotherapy drugs seem to work long after treatment ends. Examples of this include:
- CAR T-cell therapy: Researchers have found cancer-fighting CAR T cells in the blood of survivors treated 10 years prior. These leukemia patients showed no signs of remission at that time.
- Immune checkpoint inhibitors (ICIs): In a study, ICIs caused severe side effects in some mesothelioma patients. They had to stop treatment early, but it didn't shorten their survival compared to those who kept going. This may mean the immune system continued targeting cancer cells after the ICIs had been cleared.
5: Chemo Can Be Heated to Make It More Effective
For some types of cancer, doctors recommend using heated, local chemotherapy. The drug solution is hot enough to kill cancer cells but not most healthy cells. And the heat doesn't damage the chemotherapy.
Examples of this include:
For pleural and peritoneal mesothelioma, heated chemo can be quite effective. It is usually combined with surgery but can be given on its own.
This approach would be unlikely to work with many immunotherapies, which contain functional antibodies. The heat could damage or destroy them.
Sources
Calabrò L, Bronte G, Grosso F, Cerbone L, Delmonte A, Nicolini F, et al. Immunotherapy of mesothelioma: the evolving change of a long-standing therapeutic dream. Front Immunol. 2023;14:1333661.
Danuzzo F, Sibilia MC, Vaquer S, Cara A, Cassina EM, Libretti L, et al. The role of hyperthermic intrathoracic chemotherapy (Hithoc) in thoracic tumors. Cancers (Basel). 2024 Jul 11;16(14):2513.
Elsayed HH, Elanany MEE, ElSayegh MT, Hassaballa AS, Abdel-Gayed M. Hyperthermic intrathoracic chemotherapy in patients with malignant pleural mesothelioma after cytoreductive surgical procedures: a systematic review. World J Surg Oncol. 2025 Apr 9;23(1):132.
Kalkan Z, Ebinc S, Arcagok M, Bilici A, Yildiz O, Kilickap S, et al. Efficacy of immunotherapy versus chemotherapy in advanced pleural mesothelioma: a turkish oncology group (Tog) study. Medicina (Kaunas). 2025 Mar 31;61(4):638.
Peters S, Scherpereel A, Cornelissen R, Oulkhouir Y, Greillier L, Kaplan MA, et al. First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743. Ann Oncol. 2022 May;33(5):488–99.
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Katy Moncivais, Ph.D., has more than 15 years of experience as a medical communicator. As the Medical Editor at Mesothelioma.com, she ensures our pages and posts present accurate, helpful information.
