The ImmunoVerse™

Dr. Patrick Hwu sits down with Dr. Bernie Fox, a pioneering immunologist and chief of the Laboratory of Molecular and Tumor Immunology at Providence Cancer Institute. The conversation spans the early days of immunotherapy, including their shared training roots in the NIH Surgery Branch under Dr. Steve Rosenberg, and moves into today’s cutting-edge science. Dr. Fox explains the emerging concept of “dark matter” in cancer biology — the once-dismissed non-coding regions of DNA that may play a pivotal role in tumor progression and immune targeting. He discusses how these regions are now known to produce short-lived proteins that may act as cancer drivers and immunotherapy targets. Importantly, many of these “dark antigens” are shared across tumor types and do not appear in healthy tissue, making them promising targets for vaccines, TCR therapies, and other immune-based treatments. The episode also highlights Fox’s commitment to mentorship, the evolution of the Society for Immunotherapy of Cancer (SITC), and the future potential of dark genome research in cancer and beyond. What You'll Learn • How early immunotherapy research at the NCI helped prove that genetically engineered T cells can fight cancer. • What scientists mean by the “dark genome” and why it matters in cancer. • How hidden regions of DNA can produce proteins that help tumors grow and spread. • Why many tumor antigens may come from non-canonical DNA regions rather than mutations. • How researchers are exploring vaccines and engineered T cells to target these antigens. • Why discoveries in the dark genome could impact many diseases beyond cancer.

Dr. Patrick Hwu is joined by Dr. Jedd Wolchok, director of the Sandra and Edward Meyer Cancer Center at Weill Cornell, and a global leader in immune checkpoint blockade therapy. Dr. Wolchok recounts his early days in the lab of immunotherapy legend Dr. Lloyd Old and reflects on the transformational impact of CTLA-4 and PD-1 inhibitors. A key architect of these therapies’ clinical success, he shares the stories behind the trials that reshaped treatment for melanoma and beyond. The discussion also dives into the future: tackling resistance, optimizing combinations, and staying grounded in patient-focused, translational science.

Dr. Patrick Hwu speaks with Dr. Drew Pardoll, a pioneering leader in tumor immunology and director of the Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins. Dr. Pardoll reflects on his early path into immunology and the scientific discoveries that helped establish immunotherapy as a transformative approach to cancer treatment. The conversation explores how tumors suppress immune responses within the tumor microenvironment and how understanding these immune “brakes” led to the development of immune checkpoint inhibitors, including anti–PD-1 therapies. Dr. Pardoll discusses the importance of learning from early clinical failures, the promise of combination therapies, and advances in engineered T cells. Looking ahead, the episode highlights emerging technologies such as single-cell analysis and artificial intelligence, which are accelerating discoveries across cancer research and beyond. Dr. Pardoll also shares insights on mentorship, collaboration, and the importance of sustained investment in science to continue reducing cancer mortality. What You’ll Learn from Dr. Pardoll How early clinical observations from bone marrow transplantation helped reveal the curative potential of T-cell–mediated anti-tumor immunity Why many early cancer vaccines failed clinically, and how those failures directly led to the discovery of immune checkpoint pathways The critical role of the tumor microenvironment in suppressing effective immune responses, even when tumor-specific T cells are present Why combination therapies (immunotherapy + chemotherapy, targeted therapy, or cell therapy) are essential to overcoming tumor escape and resistance Emerging advances in engineered adoptive cell therapies, including logic-gated T cells designed for improved specificity and safety How single-cell and spatial transcriptomic technologies are transforming our ability to dissect the tumor ecosystem The growing role of AI in analyzing massive immunologic datasets and accelerating discovery

Dr. Suzanne Topalian, a leader in cancer immunotherapy, shares her journey from surgical residency to groundbreaking research at Johns Hopkins. She discusses the transformative impact of PD-1 inhibitors, demonstrating tumor regression in advanced cancers. Topalian highlights the importance of tumor-infiltrating lymphocytes and explores the potential of neoadjuvant immunotherapy. With insights on biomarker research, she emphasizes collaboration and mentorship in advancing cancer treatments, all while reflecting on her passions beyond science.

Dr. Robert Vonderheide, a leading physician-scientist and director at the Abramson Cancer Center, dives into the complexities of pancreatic cancer and immunotherapy. He discusses his evolving perspective on cancer treatment, emphasizing the unique challenges of pancreatic tumors, driven by the KRAS oncogene. Vonderheide explores innovative strategies that combine KRAS inhibitors with immunotherapies like CD40 agonists to enhance immune responses. He also highlights the critical need for early detection and the importance of fostering mentorship in the field.

Dr. Patrick Hwu welcomes Dr. Sandra Demaria, Professor of Radiation Oncology and Pathology at Weill Cornell Medicine and a global leader in cancer immunology. Dr. Demaria shares her pioneering research demonstrating how radiotherapy can transform tumors unresponsive to immune checkpoint inhibitors into responsive ones—a discovery that has reshaped cancer treatment strategies worldwide.   Recorded live from the 2025 SITC Annual Meeting, this episode highlights the emerging science shaping the future of immunotherapy, including late-breaking abstracts and press program findings presented at the conference. As the current vice president of SITC, Dr. Demaria discusses the evolving synergy between radiation and immunotherapy, insights from studying the immune microenvironment and the translation of her discoveries into ongoing clinical trials. She also reflects on the collaborative energy that defines SITC and continues to drive the next generation of combination immunotherapies.

Dr. Mario Sznol, a Yale Medicine professor and Cancer Immunology Program co-director, dives into his groundbreaking work in cancer immunotherapy. He shares insights on pioneering high-dose interleukin-2 trials and the evolution of checkpoint inhibitors like anti-PD-1 and anti-CTLA-4. Discover the challenges of managing immune-related toxicities and the promise of breakthroughs in bispecific antibodies and engineered T-cells. With a focus on collaboration and innovation, Sznol emphasizes the powerful impact of immunotherapy on transforming cancer treatment.

Join Dr. Fred Locke, a pioneer in CAR T-cell therapy and Chair at Moffitt Cancer Center, as he shares his journey inspired by his father's battle with lymphoma. He discusses groundbreaking clinical trials ZUMA-1 and ZUMA-7, revealing how CAR T treatments are revolutionizing lymphoma care. Dr. Locke dives into the science behind CAR T technology, survival strategies against solid tumors, and innovative approaches like donor-derived therapies. Plus, learn how diet and exercise may enhance therapy outcomes, paving the way for outpatient care.

Dr. Thomas Gajewski, a renowned tumor immunologist at the University of Chicago, shares groundbreaking insights on 'hot' and 'cold' tumors, revolutionizing immunotherapy. He explains how the tumor microenvironment and patient genetics influence immune responses, and discusses innovative strategies to convert resistant cold tumors into responsive ones. Fascinatingly, he links the gut microbiome to immunotherapy effectiveness, revealing distinct bacterial patterns in patients. Gajewski also touches on mentorship and the role of music in building scientific community.

Dr. Elizabeth Jaffee, a prominent leader in cancer immunotherapy and Deputy Director at Johns Hopkins, shares her inspiring journey into battling pancreatic cancer. She discusses how early KRAS mutations can be targeted with vaccines to potentially prevent cancer recurrence. Dr. Jaffee emphasizes the importance of using AI in identifying high-risk patients and integrating it with genetic data for personalized prevention. She also highlights the promising results of neoadjuvant immunotherapy and the role of KRAS inhibitors in overcoming treatment resistance.