The ImmunoVerse™

Dr. Patrick Hwu welcomes Dr. Ryan Sullivan, a medical oncologist at Massachusetts General Hospital, associate professor of medicine at Harvard Medical School and chair of the Society for Immunotherapy of Cancer’s (SITC) Annual Meeting Program Committee. A leading melanoma researcher, Dr. Sullivan shares insights into the latest advances in cancer immunotherapy, including promising clinical trial results for personalized cancer vaccines that could help prevent melanoma from returning. Recorded live from the 2026 SITC Annual Meeting in Phoenix, this episode highlights groundbreaking research shaping the future of immunotherapy, including late-breaking abstracts and innovative treatment approaches presented at the conference. Dr. Sullivan discusses emerging bispecific therapies, advances in tumor-infiltrating lymphocyte (TIL) therapy and new techniques to engineer CAR T cells directly inside the body. He also explores the potential of oncolytic viruses to stimulate immune responses against brain tumors and reflects on how once-experimental approaches are opening new possibilities for treating cancer.

Dr. Patrick Hwu sits down with Dr. Patrick Forde, a leading expert in lung cancer immunotherapy, to explore how advances in immunotherapy are changing the way lung cancer is treated. They discuss Dr. Forde’s pioneering research on using immunotherapy before surgery, an approach that has helped improve outcomes for patients with earlier-stage lung cancer. They also explore why some lung cancers respond better to immunotherapy than others, the importance of genetic testing in selecting the right treatment and the growing role of personalized medicine. Dr. Forde also shares insights from his career, differences in cancer care between the U.S. and Ireland, and his approach to mentoring the next generation of researchers. What You'll Learn from Dr. Patrick Forde How the CheckMate 816 trial made neoadjuvant chemoimmunotherapy a standard of care for stage II and III lung cancer Why immunotherapy before surgery may work better than after surgery Which lung cancers respond to immunotherapy, and why never-smoker and EGFR-mutant tumors usually need targeted therapy Why biomarker testing (EGFR, PD-L1) before treatment matters for every lung cancer patient How U.S. and European cancer care differ in surgical expertise and drug access

Dr. Patrick Hwu sits down with Dr. Ira Mellman, president of research at the Parker Institute for Cancer Immunotherapy, to explore the science behind immune activation and its application to cancer treatment. Together, they discuss Dr. Mellman’s pioneering work on dendritic cells and endosomes, the cancer-immunity cycle, and why checkpoint inhibitors only work when enough tumor-fighting T cells are already present. Dr. Mellman explains how personalized cancer vaccines could generate stronger immune responses, the challenges of making these treatments scalable, and why ambitious science and thoughtful mentorship are essential to advancing immunotherapy. What You’ll Learn From Dr. Ira Mellman How endosomes and dendritic cells shape antigen presentation and T-cell activation The role of the cancer-immunity cycle in understanding immune responses and treatment resistance Why rate-limiting steps in the cancer-immunity cycle matter for immunotherapy How cancer vaccines can generate antigen-specific T-cell responses The importance of innate immune signals in developing effective cancer vaccines Emerging approaches to personalized cancer vaccines and their scalability

Dr. Patrick Hwu speaks with Dr. Yvonne Chen about how engineering is shaping the future of CAR T-cell therapy. They discuss logic-gated CAR T-cells, strategies to prevent tumor escape, and new approaches for treating solid tumors such as glioblastoma. Dr. Chen also shares how her engineering background influences both her research and mentorship style.

Dr. Patrick Hwu speaks with Dr. John Wherry, a world-renowned expert in T-cell biology and director of the Institute for Immunology and Immune Health at the University of Pennsylvania. Dr. Wherry reflects on his early interest in science and explains how chronic stimulation can cause T cells to become exhausted, limiting their ability to fight cancer and persistent infections. The conversation explores how immunotherapies such as PD-1 blockade can reinvigorate exhausted T cells, why some patients do not respond, and how the tumor microenvironment and epigenetic scarring shape immune function. Dr. Wherry also discusses the future of personalized immunotherapy, the importance of mentorship and collaboration, and how music inspires creativity in both science and life. What You’ll Learn with Dr. John Wherry Why T cells "burn out" and what that means for cancer treatment How today's most successful immunotherapies work to release the immune system's brakes Why immunotherapy doesn't work for every patient—and how researchers are working to change that How a tumor's "neighborhood" can influence the immune system's ability to fight cancer The promise of reprogramming exhausted immune cells to create more effective cancer treatments Where cancer immunotherapy is headed next, from personalized approaches to new vaccine strategies

Dr. Patrick Hwu speaks with Dr. Miriam Merad, a leading physician-scientist in dendritic cell and macrophage biology at the Icahn School of Medicine at Mount Sinai. Dr. Merad reflects on her path from medicine to immunology and discusses how tissue-resident macrophages help maintain organ health but can also be fooled by tumors into supporting cancer growth. The conversation explores ways to reprogram macrophages for cancer treatment, the link between aging, inflammation and cancer risk, and the importance of multidisciplinary collaboration, data science and sustained research investment in advancing future cures. What You’ll Learn with Dr. Miriam Merad The role of macrophages in cancer, inflammation and tissue repair Why cancer can exploit the body's natural wound-healing processes New immunotherapy approaches that target and reprogram macrophages The connection between aging, chronic inflammation and cancer risk The future of macrophage-based cancer treatments Mentorship strategies for developing the next generation of immunology leaders

Dr. Patrick Hwu sits down with Dr. Jennifer Wargo, Professor of Surgical Oncology and Genomic Medicine, leader of the platform for innovative microbiome and translational research at The University of Texas MD Anderson Cancer Center, to discuss how the tumor microbiome and host factors shape cancer development and response to immunotherapy. Together, they explore the growing evidence that cancer is influenced not only by tumor genetics and the immune system but also by the communities of bacteria that live within and around tumors. Dr. Wargo explains how differences in the gut and tumor microbiome can affect immune activation, potentially altering how well patients respond to treatments such as immune checkpoint inhibitors. The conversation highlights how diet, antibiotics, and other environmental exposures may shift microbial composition, which in turn can influence systemic immunity and tumor behavior. They also discuss how this emerging field is opening new possibilities for predicting treatment response and designing strategies to improve immunotherapy effectiveness. What You’ll Learn with Jennifer Wargo • How the gut microbiome affects immunotherapy response. • Why some bacteria help the immune system fight cancer. • How microbes can contribute to treatment resistance. • Why dietary fiber may improve cancer outcomes. • How microbiome-based therapies could shape future treatment.

Dr. Patrick Hwu sits down with Dr. Greg Delgoffe, professor of immunology at the University of Pittsburgh and director of the Tumor Microenvironment Center at UPMC Hillman Cancer Center, to explore how the tumor microenvironment functions as a complex, dynamic ecosystem that shapes the success or failure of cancer immunotherapy. Together, they unpack how tumors are far more than just cancer cells—consisting instead of diverse populations of immune cells, stromal cells, and cancer cells all interacting within a shared and often hostile environment. Dr. Delgoffe explains how cancer cells actively reshape that environment by competing for and consuming key nutrients, effectively starving immune cells and limiting their ability to mount an effective response. The conversation dives into the emerging field of immunometabolism, revealing how metabolic competition within tumors can determine immune cell function and ultimately influence whether immunotherapy works. What You’ll Learn with Dr. Delgoffe What the tumor microenvironment is and why it’s more than just cancer cells. How immune cells and tumor cells compete for space, nutrients and control. How metabolism shapes immune function and cancer’s ability to evade attack. Why understanding these cellular “interactions” is key to improving immunotherapy.

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.