Enlisting the Immune System in the War on Cancer

Episode Summary

Executive Summary: The episode examines cancer immunotherapy with UCSF’s Lawrence Fong, explaining how treatments like checkpoint inhibitors harness the immune system, why some cancers respond dramatically, and why others remain resistant. It highlights UCSF’s clinical and research infrastructure—plus collaborations with Parker Institute, Merck, and industry sponsors—to better profile tumors, study immune responses, and develop more precise therapies.

Main Topics: What cancer immunotherapy is (Priority: 5/5): Fong defines immunotherapy as using drugs to activate a patient’s own immune system rather than directly killing cancer cells, marking a major shift from chemotherapy and radiation. Why immunotherapy can be transformative (Priority: 5/5): These therapies can work across multiple cancer types and produce unusually durable responses, including long-term remissions that may last a decade or more. Why immunotherapy is difficult (Priority: 5/5): Challenges include incomplete understanding of immune biology, tumor heterogeneity, and cancer’s ability to evade immune detection or develop resistance. Precision medicine and biomarkers (Priority: 4/5): The discussion covers PD-L1 testing, especially in lung cancer, as an imperfect but clinically useful biomarker to help select patients for anti-PD-1 therapy. UCSF’s Cancer Immunotherapy Program (Priority: 5/5): Fong describes a clinic built to deliver complex immunotherapies safely while simultaneously collecting patient samples to turn treatment into a research engine. Collaborative research through the Parker Institute and Immunoprofiler (Priority: 4/5): UCSF is working with a six-center consortium and industry partners to run larger trials, engineer T cells, study resistance, and classify cancers by immune features rather than tissue of origin. New insights into immune activation (Priority: 3/5): Research from Matthew Spitzer and collaborators suggests immune activation occurs in blood and lymph nodes, with similar activation observed in patients receiving checkpoint inhibitors.

Key Arguments: Immunotherapy changes the treatment paradigm by relying on the patient’s immune system to fight cancer instead of directly targeting tumor cells. Immune checkpoint inhibitors are effective because they remove inhibitory brakes on existing immune responses rather than creating entirely new ones. Cancer can evade immunity through tumor evolution and heterogeneity, so not all cells in a tumor respond the same way. The ability of a single immunotherapy drug to treat many cancers is a key reason the field is considered transformative. Durable responses are a defining advantage: some patients remain cancer-free for 10+ years after treatment. Biomarkers like PD-L1 help guide treatment selection, but current tests are still incomplete and fail to predict all responders. Better understanding of each patient’s immune system may be as important as tumor genetics in predicting response. Dedicated immunotherapy clinics can simultaneously improve patient care and accelerate discovery by integrating treatment with sample collection and analysis. Large, multi-center collaborations are needed to study resistance and develop more potent engineered cell therapies. A future direction is to classify cancers by immune behavior, not just the organ where they originated.

Data Points: Duration of durable response: 10+ years - Fong says some immunotherapy responders have remained cancer-free for more than a decade after treatment. Number of cancer types affected by a single drug: A dozen or more - He notes that checkpoint inhibitors such as PD-1/PD-L1 antibodies can work across many different cancers. Parker Institute consortium size: 6 cancer centers - UCSF works with the Parker Institute alongside five other centers to coordinate trials and research. Immunoprofiler funding: $10 million - The UCSF Immunoprofiler project is backed by AbbVie, Amgen, and Bristol Myers. Immunoprofiler duration: 2 years - The project is described as a two-year effort to classify cancers by immune response. Resistance trial enrollment: 200 to 300 patients - A Parker Institute/Merck study will investigate resistance to anti-PD-1 antibodies in lung and head and neck cancer. FDA-approved first-line use: Metastatic lung cancer - Fong explains that anti-PD-1 immunotherapy can be the first treatment when PD-L1 is highly expressed.

Pivotal Quotes: "These drugs are actually serving to turn on a patient's own immune system, and then we're relying on that patient's own immune system to actually kill the cancer cell." — Lawrence Fung: Definition of cancer immunotherapy and how it differs from chemotherapy/radiation. "The future is now." — Lawrence Fung: His view that immunotherapy has already become standard of care for some cancers. "We're really in early days in terms of precision medicine with immunotherapy." — Lawrence Fung: On the need for better biomarkers and immune-system profiling to guide treatment.

Implications: Immunotherapy is already reshaping oncology, but broader success depends on better biomarkers, immune profiling, and collaborative trials. Patients may increasingly receive treatments tailored to immune behavior, not just tumor origin.