In 2018 the Nobel Prize in Physiology or Medicine went to James P. Allison and Tasuku Honjo “for their discovery of cancer therapy by inhibition of negative immune regulation.” Their work helped turn a long-shot idea into routine care: instead of only cutting out, burning or poisoning a tumor, doctors can try to teach the patient’s own immune system to go after it.
That was the older playbook. Cancer treatment used to focus on killing or removing cancer cells with chemotherapy, surgery or radiation. Immunotherapy is not one treatment but a group of them. Some boost the immune system to work against the cancer, while others train it to find and attack cancer cells.
The main approaches
Checkpoint inhibitors are antibodies against PD-1/PD-L1 or CTLA-4, and they are the two types available to patients today. These proteins help keep immune responses in check. Blocking them lets T cells press the attack. The drugs are approved for some patients with melanoma, breast, bladder, cervical, colon, lung and head and neck cancers, and Hodgkin lymphoma. In metastatic melanoma they showed an improvement in overall survival for the first time in many years of research, with a growing group of patients benefiting long-term. Newer inhibitors aimed at LAG-3, TIM3 and TIGIT have been studied in trials but are not yet approved for widespread use.
Adoptive cell therapy takes a patient’s own T cells out of the body, multiplies or engineers them, and puts them back. Steven Rosenberg and colleagues showed the first proof of concept in 1988, when expanded tumor-infiltrating lymphocytes (TILs) given with high-dose interleukin-2 shrank tumors in patients with metastatic melanoma. In 2024 the FDA granted accelerated approval to lifileucel, a TIL therapy for metastatic melanoma, and to afamitresgene autoleucel (Tecelta), the first TCR-T therapy for solid tumors.
CAR-T therapy engineers T cells to carry a synthetic receptor aimed at a tumor antigen. The first one approved, Kymriah, opened the field. The FDA has since cleared several CAR-T therapies for blood cancers, including B-cell acute lymphoblastic leukemia, B-cell lymphoma and multiple myeloma. Solid tumors are a harder target, and results there remain limited.
Older tools
BCG, a vaccine first used against tuberculosis, is one of the oldest forms of cancer immunotherapy. It later proved useful against bladder cancer. Rituximab, approved in 1997 for B-cell lymphoma, brought monoclonal antibodies into cancer care. Sipuleucel-T, a cancer vaccine made from a patient’s dendritic cells, was the first FDA-approved cell-based immunotherapy.
What patients should know
Responses vary with the type of disease, a patient’s genetic background and environmental factors. A supercharged immune system can also turn on healthy tissue. These immune-related adverse events are serious enough that UChicago Medicine runs a dedicated clinic for them.
Studies in various cancers have reported significant gains in survival and disease-free periods. Combining cell-based immunotherapy with conventional treatment is reported to improve its efficacy by 20 to 30 percent. Anyone weighing these options should talk to their own oncologist. Consult your doctor for medical advice.
