Immunotherapy is used to treat more than a dozen types of cancer, several allergic conditions, and a growing number of autoimmune diseases. In cancer care, it can be a first-line treatment for advanced melanoma and certain lung cancers, a later option when other treatments have failed, or even a pre-surgical strategy for early-stage tumors. The timing depends on the specific cancer type, how far it has spread, and whether your tumor carries certain biological markers that predict a response.
How Immunotherapy Works
Your immune system has built-in brakes, called checkpoints, that prevent it from attacking your own healthy tissue. Many cancers exploit these brakes to hide from immune cells. The most widely used form of immunotherapy, checkpoint inhibitors, releases those brakes so your immune system can recognize and destroy cancer cells. These drugs now account for the majority of immunotherapy prescriptions in oncology.
Other approaches work differently. In T-cell transfer therapy (including CAR-T), doctors remove immune cells from your body, engineer or select the most effective ones in a lab, multiply them, and infuse them back into your bloodstream. Monoclonal antibodies are lab-made proteins that attach to specific markers on cancer cells, essentially tagging them for destruction. Each type is suited to different cancers and different points in treatment.
Cancers Treated as a First Option
For several advanced cancers, immunotherapy is now standard from the start, not something reserved for after chemotherapy fails. Advanced melanoma was the first major success story. A combination of two checkpoint inhibitors produces a response rate of 58% in metastatic melanoma, compared to 19% with just one of those drugs alone. That combination has been a first-line option since its FDA approval in 2015.
Non-small cell lung cancer (NSCLC) is the other major area where immunotherapy routinely comes first. Patients with stage IV or recurrent NSCLC whose tumors don’t carry certain genetic mutations are typically offered a checkpoint inhibitor alongside chemotherapy as their initial treatment. Multiple approved regimens pair checkpoint inhibitors with platinum-based chemotherapy for both squamous and nonsquamous subtypes. For patients whose tumors strongly express the PD-L1 protein, a checkpoint inhibitor alone may be enough without adding chemotherapy.
Head and neck squamous cell cancer, extensive-stage small cell lung cancer, and advanced triple-negative breast cancer also have approved first-line regimens that include immunotherapy combined with chemotherapy.
When It’s Used After Other Treatments Fail
Many immunotherapy approvals are for patients who have already tried one or more rounds of other treatment. CAR-T cell therapy, for example, is typically reserved for blood cancers that have relapsed or stopped responding to standard options. Current approved CAR-T products treat large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, certain forms of leukemia, and chronic lymphocytic leukemia. In most cases, patients must have gone through at least one or two prior lines of therapy before qualifying.
This later-line use applies to many solid tumors as well. For cancers where immunotherapy isn’t the standard first approach, it often becomes an option after chemotherapy, targeted therapy, or radiation has been tried and the cancer has progressed.
Before and After Surgery
Immunotherapy isn’t limited to advanced or inoperable cancers. In October 2024, the FDA approved a checkpoint inhibitor for use both before and after surgery in patients with resectable non-small cell lung cancer (tumors 4 cm or larger, or with lymph node involvement). Patients receive the drug alongside chemotherapy for up to four cycles before surgery, then continue the immunotherapy alone for up to a year afterward. This approach, tested in a trial of 461 patients with stage IIA through select stage IIIB disease, aims to shrink the tumor before it’s removed and reduce the risk of recurrence.
Similar before-surgery (neoadjuvant) and after-surgery (adjuvant) strategies are being used or studied in melanoma, bladder cancer, and kidney cancer.
Biomarkers That Determine Eligibility
Not every patient with the same cancer type will be offered immunotherapy. Doctors test tumors for specific biological markers that predict whether the treatment is likely to work.
- PD-L1 expression: This measures how much of a particular protein appears on tumor cells. A common threshold is 1% or higher, meaning at least 1% of tumor cells display the protein. For some lung cancer indications, higher levels (50% or above) may qualify you for immunotherapy without chemotherapy.
- Tumor mutational burden (TMB): This counts how many mutations exist in the tumor’s DNA. Tumors with 10 or more mutations per megabase are considered “high TMB” and tend to respond better. In NSCLC, the response rate jumps from about 20% in low-TMB tumors to 35% in high-TMB tumors. In melanoma, it rises from 32% to 58%.
- Microsatellite instability (MSI-H): Tumors with a high degree of instability in their DNA repair systems often respond well to immunotherapy regardless of where in the body the cancer originated. This was the basis for the first cancer drug approval based entirely on a genetic feature rather than a tumor’s location.
Your oncologist will typically order these tests before recommending a checkpoint inhibitor. Some cancers, like melanoma, respond well enough across the board that biomarker testing is less of a gatekeeper, while for others, like pancreatic cancer (which has a response rate of only about 4%), immunotherapy is rarely appropriate.
Combination With Chemotherapy
In many cases, immunotherapy works best when paired with traditional chemotherapy rather than used on its own. Chemotherapy can kill cancer cells in ways that make them more visible to the immune system, essentially priming the body for a stronger immune response. Combinations of immunotherapy with chemotherapy now represent the most common approved regimens across cancer types.
The pattern is consistent across lung, head and neck, breast, and small cell lung cancers: adding a checkpoint inhibitor to a standard chemotherapy backbone improves response rates and extends survival compared to chemotherapy alone. In some settings, two different immunotherapy drugs are combined with each other, as in the melanoma regimen that pairs two checkpoint inhibitors targeting different pathways. Dual immunotherapy combinations also have approvals in kidney cancer and lung cancer.
Beyond Cancer: Allergies and Autoimmune Conditions
Immunotherapy has a long history outside of oncology. Allergen-specific immunotherapy, commonly known as allergy shots or sublingual tablets, has been used for over a century to desensitize people to triggers like pollen, dust mites, and insect venom. This works in the opposite direction from cancer immunotherapy: instead of ramping up the immune system, it gradually teaches it to tolerate a harmless substance it’s been overreacting to.
Monoclonal antibodies originally developed using immunotherapy principles are also used for autoimmune conditions like rheumatoid arthritis, psoriasis, and inflammatory bowel disease. These drugs target specific immune pathways that drive inflammation, calming an overactive immune system rather than unleashing it.
Who May Not Be a Candidate
Certain health conditions can make immunotherapy too risky. Active autoimmune diseases are generally a contraindication for cancer checkpoint inhibitors, because unleashing the immune system could trigger a severe autoimmune flare. Patients on immunosuppressive medications, including organ transplant recipients taking anti-rejection drugs, face a similar concern: checkpoint inhibitors could override the immunosuppression and cause organ rejection.
Pregnancy is another contraindication, as is uncontrolled asthma for allergen-specific immunotherapy. Patients with primary immune deficiencies may not generate a strong enough response for the treatment to work. These aren’t always absolute barriers. Oncologists sometimes use immunotherapy in patients with well-controlled autoimmune conditions under close monitoring, but the decision involves weighing the cancer risk against the potential for serious immune side effects.