A PERSPECTIVE Immunotherapy has emerged in the last decade alongside surgery, chemotherapy, radiation, and targeted therapy as a pillar of cancer therapy. Notably, immune checkpoint therapy (ICT) agents against the T cell checkpoints CTLA-4 and PD-1/PD-L1 have provided long-term remissions against previously intractable cancers, such as metastatic melanoma and lung cancer. The combination of the two provides an even higher response rate and is now FDA approved as a standard of care. Since anti-CTLA-4 and anti-PD-1/PD-L1 antibodies globally unleash T cell responses, they are not specific for a given tumor type, and clinical data indicate responses against a wide range of cancers, including renal cell carcinoma, lung cancer, bladder cancer, hepatocellular carcinoma, and many others. These immunotherapy agents drive diverse immune responses and enable formation of antigen-specific memory responses, thereby providing a “living drug” with the capability to eliminate the tumor indefinitely. Both anti-CTLA-4 and anti-PD-1/ PD-L1 agents have been FDA approved as monotherapy and as combination therapies, including combinations with chemotherapy and targeted therapies such as tyrosine kinase inhibitors (TKIs). Most recently, another immune checkpoint agent, anti-LAG-3, was approved in combination with anti-PD-1 for the treatment of patients with metastatic melanoma revealing that there are additional inhibitory receptors that can be blocked for therapeutic benefit. Whereas ICT provides lasting remissions to some patients with specific cancers, many patients do not respond to treatment. Cancers with few immune cells in the tumor such as pancreatic cancer and glioblastoma generally do not respond. In addition, other immunosuppressive Looking to the Future of Immunology James P. Allison, PhD, FAACR 2018 Nobel Laureate in Physiology or Medicine Vice President, Immunobiology; Chair, Department of Immunology; Executive Director, Immunotherapy Platform; Director, James P Allison Institute; Olga Keith Weiss Distinguished University Chair for Cancer Research The University of Texas MD Anderson Cancer Center Houston, Texas Padmanee Sharma, MD, PhD Professor of Genitourinary Medical Oncology; Professor of Immunology; Scientific Director of Immunotherapy Platform; Associate VP of Immunobiology; Director of Scientific Programs, James P. Allison Institute MD Anderson Cancer Center Houston, Texas AACR Cancer Progress Report 2023 Immunotherapy: Pushing the Frontier of Cancer Medicine 104
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