What Is Immunotherapy? How It Differs From Chemo and Radiation

Immunotherapy is a category of cancer treatment that works by directing the patient's own immune system to recognize and destroy cancer cells, rather than by directly poisoning or irradiating them the way chemotherapy and radiation do. The major immunotherapy approaches — checkpoint inhibitors, CAR T-cell therapy, monoclonal antibodies, cancer vaccines, and cytokine therapy — have distinct mechanisms but share this common feature, and several drugs in this class (pembrolizumab, nivolumab, ipilimumab) are FDA-approved and in routine clinical use. Response rates and side-effect profiles differ substantially from conventional treatment, and both vary a great deal by cancer type — immunotherapy is not a uniform "better" alternative to chemo or radiation, it is a mechanistically different tool that works well for some cancers and patients and poorly for others.

Three Treatments, Three Different Targets

The clearest way to understand immunotherapy is to compare what each of the three treatment types actually attacks. Chemotherapy uses cytotoxic drugs that interfere with cell division; because cancer cells divide rapidly, they're especially vulnerable, but chemo also damages other fast-dividing normal cells — hair follicles, the lining of the gut, bone marrow — which is why hair loss, nausea, and low blood counts are hallmark chemo side effects. As the American Cancer Society puts it, chemo works "at just the right dose to kill the cancer cells while sparing as many normal cells as possible," and most normal cells recover while cancer cells are less able to.

Radiation therapy works differently: it uses high-energy beams (or, less commonly, internal radioactive sources) to damage the DNA of cells in a defined area, causing them to stop dividing or die. The National Cancer Institute notes this is a local treatment in its most common form — a patient with lung cancer, for example, receives radiation only to the chest — though some radiation-based treatments, like radioactive iodine for thyroid cancer, do travel systemically through the bloodstream.

Immunotherapy doesn't directly kill cells at all. Instead, it works "with your body's immune system to kill cancer cells or limit their growth," per the American Cancer Society. The rationale is that the immune system can, in principle, already recognize and eliminate abnormal cells — but cancer cells develop ways to evade detection, including genetic changes that hide them from immune surveillance, surface proteins that deactivate immune cells that approach them, and alterations to the surrounding tissue that blunt immune responses. Immunotherapy is designed to overcome those evasion tactics rather than to attack the tumor directly.

Checkpoint Inhibitors: Releasing the Brakes

The most widely used immunotherapy class is immune checkpoint inhibitors. The immune system relies on "checkpoint" proteins to keep T cells from attacking healthy tissue — but some tumors exploit these same checkpoints (such as PD-1/PD-L1 and CTLA-4) to switch off the T cells that would otherwise attack them. Checkpoint inhibitor drugs block these checkpoint interactions, releasing the brake and allowing T cells to attack the cancer.

Real, FDA-approved examples include pembrolizumab (Keytruda) and nivolumab (Opdivo), both PD-1 inhibitors used across a range of cancers including melanoma and non-small cell lung cancer, and ipilimumab (Yervoy), a CTLA-4 inhibitor that was the first checkpoint inhibitor ever approved by the FDA, in March 2011, for metastatic melanoma.

CAR T-Cell Therapy and Other Adoptive Cell Therapies

CAR T-cell therapy is a form of adoptive cell therapy: a patient's own T cells are collected, genetically engineered in a lab to express a chimeric antigen receptor (CAR) that recognizes a specific marker on cancer cells, expanded to large numbers, and infused back into the patient. Tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta) were among the first CAR T-cell therapies approved by the FDA, both engineered to target CD19, a protein commonly found on cancerous B cells, and both initially approved for certain blood cancers. Related approaches in this category include tumor-infiltrating lymphocyte (TIL) therapy and engineered T-cell receptor (TCR) therapy.

Monoclonal Antibodies, Cancer Vaccines, and Cytokines

Monoclonal antibodies are lab-made proteins engineered to bind to specific targets on cancer cells, marking them for destruction by the immune system or blocking signals the cancer needs to grow; some are also engineered as antibody-drug conjugates that deliver a cytotoxic payload directly to the tumor, or as bispecific antibodies (like blinatumomab) that physically link a T cell to a cancer cell.

Cancer vaccines work differently from preventive vaccines like the HPV vaccine — therapeutic cancer vaccines expose the immune system to cancer-specific antigens to trigger an attack on existing disease, such as sipuleucel-T for prostate cancer.

Cytokine therapy uses signaling proteins — interferons and interleukins — to broadly stimulate immune cell activity; it was among the earliest immunotherapy approaches and remains in limited use for cancers such as kidney cancer and melanoma.

How Side Effects Differ

Because immunotherapy works through the immune system rather than through direct cytotoxicity, its side-effect pattern is distinct from classic chemo and radiation toxicity. Chemo's signature effects — hair loss, nausea and vomiting, and low blood counts — stem from damage to healthy fast-dividing cells. Radiation's side effects are typically localized to the treated area (such as skin irritation or fatigue near the treatment site).

Immunotherapy, by contrast, can cause immune-related adverse events (irAEs): because the treatment amplifies immune activity generally, that activated immune system can sometimes attack healthy organs and tissues, not just the tumor. The American Cancer Society lists skin changes, fatigue, flu-like symptoms, gastrointestinal symptoms, and endocrine (hormonal) changes among the possible effects, alongside classic cytotoxic-style symptoms in some cases. Research reviews of checkpoint inhibitor toxicity (including guidance published by the American Society of Clinical Oncology) describe irAEs as capable of affecting nearly any organ system — skin, colon, liver, lungs, and endocrine glands are among the more commonly reported sites — which is mechanistically different from the direct cell-cycle disruption chemo and radiation cause.

Response Rates Vary Enormously by Cancer Type

It's worth being direct about a point that's easy to lose in enthusiasm about immunotherapy: it does not work equally well across cancer types, or for all patients within a given cancer type. Checkpoint inhibitors, for instance, tend to show stronger and more durable responses in cancers with high mutational burden (which produce more abnormal proteins for the immune system to recognize), such as melanoma and some lung cancers, and more modest results in others. CAR T-cell therapy has so far shown its strongest results in certain blood cancers and has been harder to translate effectively to solid tumors. This variability is a major, ongoing area of research, not a settled matter — immunotherapy is a mechanism, not a guarantee.

Bottom Line

Chemotherapy and radiation kill cancer cells directly — chemo through cytotoxic drugs that disrupt cell division everywhere in the body, radiation through localized DNA damage in a targeted area — and both inevitably damage some healthy cells along the way, producing well-known side effects like hair loss, nausea, and localized tissue irritation. Immunotherapy takes a different route: it works by helping or redirecting the patient's own immune system to recognize and attack cancer cells, using approaches like checkpoint inhibitors (pembrolizumab, nivolumab, ipilimumab), CAR T-cell therapy (tisagenlecleucel, axicabtagene ciloleucel), monoclonal antibodies, cancer vaccines, and cytokines. Because it acts through immune activation rather than direct cytotoxicity, its side-effect profile is different in kind — immune-related adverse events rather than classic chemo/radiation toxicity — and its effectiveness varies widely by cancer type and by patient. None of these three approaches is categorically "better"; they are different tools, often used in combination, matched to the biology of a specific cancer.