Cancer immunotherapy has revolutionized oncology by activating the patient’s own immune system to recognize and eliminate cancer cells, producing durable responses in previously treatment-refractory malignancies. Unlike direct cytotoxic or targeted approaches, immunotherapy leverages the immune system’s specificity, adaptability, and memory to achieve sustained tumor control.
What Is Cancer Immunotherapy?
Cancer immunotherapy encompasses diverse strategies including immune checkpoint inhibitors, cellular therapies, cytokines, and cancer vaccines. These approaches share the goal of overcoming immune evasion mechanisms that allow tumors to escape detection and destruction by T cells and other immune effectors.
Drug Classes and Mechanisms
Immune checkpoint inhibitors (ICIs) block inhibitory receptors on T cells that tumors exploit to suppress anti-tumor immunity. Anti-PD-1 antibodies including pembrolizumab and nivolumab block the programmed death-1 receptor, preventing its interaction with PD-L1 and PD-L2 on tumor cells and antigen-presenting cells. Anti-PD-L1 antibodies (atezolizumab, durvalumab, avelumab) block the ligand directly. Anti-CTLA-4 antibodies such as ipilimumab block CTLA-4, an inhibitory receptor that regulates early T cell activation in lymph nodes. PD-1 and CTLA-4 blockade have complementary mechanisms and are combined in some regimens.
CAR-T cell therapy involves extracting a patient’s T cells, genetically engineering them to express a chimeric antigen receptor targeting a tumor-associated antigen (such as CD19 in B cell malignancies), and reinfusing them after lymphodepleting chemotherapy. Tisagenlecleucel and axicabtagene ciloleucel target CD19 and produce high response rates in relapsed or refractory B cell acute lymphoblastic leukemia and non-Hodgkin lymphoma.
Cytokine therapy uses recombinant immune signaling proteins. High-dose interleukin-2 (IL-2) activates T cell and natural killer cell proliferation, producing durable responses in metastatic melanoma and renal cell carcinoma at the cost of significant toxicity. Interferon-alpha has immunomodulatory and anti-proliferative effects used in melanoma and hematologic malignancies.
Cancer vaccines aim to stimulate T cell responses against tumor-specific or tumor-associated antigens. Sipuleucel-T is an autologous dendritic cell vaccine for metastatic castration-resistant prostate cancer. Neoantigen vaccines targeting patient-specific tumor mutations are under investigation.
Therapeutic Uses
PD-1 inhibitors are approved across an expanding range of cancers including melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancer, Hodgkin lymphoma, and mismatch repair-deficient tumors of any origin. Ipilimumab is used in melanoma and in combination with nivolumab for multiple tumors. CAR-T therapy is currently limited to hematologic malignancies.
Adverse Effects
Immune-related adverse events (irAEs) result from non-specific immune activation and can affect any organ system. Common irAEs include dermatitis, colitis, hepatitis, pneumonitis, thyroiditis, and hypophysitis. Severe irAEs may require treatment interruption, high-dose corticosteroids, and other immunosuppressive agents. CAR-T therapy causes cytokine release syndrome (fever, hypotension, multiorgan dysfunction) and neurotoxicity requiring specialized management.
Key Clinical Considerations
Biomarkers including PD-L1 expression, tumor mutational burden, and microsatellite instability predict response to ICIs. Pseudoprogression (transient tumor enlargement before response) can complicate radiographic assessment. irAEs may occur at any time during or after treatment and require prompt recognition and management. CAR-T therapy is limited to specialized centers due to acute toxicity management requirements.
Conclusion
Cancer immunotherapy has established a new pillar of cancer treatment, offering durable remissions for patients with advanced cancers that were previously considered incurable. Ongoing research aims to extend benefit to more patients through combination strategies, novel targets, and improved management of immune-related toxicity.
