The ImmunoVerse™

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.

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. Patrick Hwu welcomes Dr. Suzanne Topalian, Bloomberg-Kimmel Professor of Cancer Immunotherapy at Johns Hopkins and Director of the Melanoma Program at the Sidney Kimmel Comprehensive Cancer Center. Dr. Topalian shares her journey from surgical residency to groundbreaking research in tumor-infiltrating lymphocytes (TILs) and immune checkpoint blockade. She discusses the evolution of PD-1 inhibition, her contributions to biomarker discovery, and her work expanding immunotherapy to rare cancers like Merkel cell carcinoma. Dr. Topalian also explores the promise of neoadjuvant immunotherapy, the importance of persistence in research, and the role of mentorship in shaping the next generation of cancer scientists. Throughout the conversation, she emphasizes the collaborative, patient-centered approach that has defined her career and continues to drive advances in cancer immunotherapy. Key Takeaways Immunotherapy translation is a marathon - TIL development required decades from concept to FDA approval. Persistence, infrastructure scaling, and multi-disciplinary collaboration were critical. Helper T cells and other immune subsets deserve continued focus - early CD4 work opened the door to a broader understanding of immune network contributions beyond cytotoxic T cells. Checkpoint inhibitors transformed expectations for advanced disease - first-in-human PD-1 trials demonstrated tumor regression in treatment-refractory melanoma, lung, and renal cancers—creating a new standard of care and catalyzing pharmaceutical development. Neoadjuvant immunotherapy offers biological and clinical advantages - treating tumors in situ may better prime tumor-resident T cells and reduce microscopic metastases before surgical resection. Manufacturing scale and technological innovation matter - transitioning from wells to bioreactor-type systems enabled effective TIL dosing thresholds and clinical response.

Dr. Patrick Hwu welcomes Dr. Robert Vonderheide, director of the Abramson Cancer Center and Vice Dean for Cancer Programs at the University of Pennsylvania’s Perelman School of Medicine. Dr. Vonderheide shares his journey from early skepticism about cancer immunotherapy to pioneering work in tumor antigen discovery, vaccine development, and activating the CD40 pathway. He discusses the unique challenges of pancreatic cancer, including its suppressive microenvironment and the role of the KRAS oncogene, and explores strategies combining targeted therapy with immunotherapy to generate effective T-cell responses. Dr. Vonderheide also highlights the promise of early detection and interception, the potential of CD40 agonists, and the importance of mentorship in training the next generation of cancer researchers, emphasizing the collaborative, innovative spirit that continues to drive advances 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. Patrick Hwu welcomes Dr. Mario Sznol, professor of medicine at Yale School of Medicine and co-director of the Cancer Immunology Program at Yale Cancer Center. Dr. Sznol shares his journey from early work with high-dose interleukin-2 at the NCI to leading pivotal trials in checkpoint blockade and combination immunotherapies. He discusses the science behind cytokines, immune checkpoints, bispecific antibodies, and T-cell therapies, along with strategies for managing immune-related toxicities. Dr. Sznol also reflects on the collaborative, innovative spirit of the field and the next wave of therapies poised to further transform cancer treatment. What You’ll Learn from Dr. Sznol How the earliest trials of interleukin-2 paved the way for modern immunotherapy The inside story of developing and combining anti–PD-1 and anti–CTLA-4 checkpoint inhibitors Why durable cures in metastatic melanoma and kidney cancer were once thought impossible — and how that changed How scientists learned to manage immune-related toxicities and make combination immunotherapy safer What’s next in the field: bispecific antibodies, T-cell engagers, and engineered cell therapies The importance of collaboration, persistence, and even a little fun (“ImmunoTennis”) in advancing science Access more show notes, links and transcript here: https://www.moffitt.org/about-moffitt/podcasts/immunoverse/cytokines-to-checkpoint-blockade

Dr. Patrick Hwu welcomes Dr. Fred Locke, chair of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center. Dr. Locke shares his personal and professional journey into CAR T-cell therapy, shaped in part by his own father’s cancer battle. A leader in pivotal clinical trials, Dr. Locke explains how engineered T cells are transforming lymphoma treatment — offering durable, sometimes curative responses. He discusses the science behind CAR T-cell manufacturing, trial design and its growing applicatio to diseases like multiple myeloma, along with future innovations in cellular immunotherapy. What You’ll Learn from Dr. Locke How a personal family experience inspired Dr. Locke’s passion for immunotherapy The story behind pivotal CAR T clinical trials (ZUMA-1 and ZUMA-7) and their FDA approvals What makes CAR T therapy so effective in blood cancers — and the challenges with solid tumors Innovative approaches on the horizon: donor-derived CAR Ts, TIL therapy, and engineered TCR therapies Why diet, exercise, and prehabilitation may improve immune cell therapy outcomes How Moffitt is scaling CAR T for outpatient treatment and community hospital access Access more show notes, links and transcript here: https://www.moffitt.org/about-moffitt/podcasts/immunoverse/future-of-cellular-treatments/

Dr. Patrick Hwu sits down with Dr. Thomas Gajewski, a leader in tumor immunology at the University of Chicago. Dr. Gajewski discusses his pioneering work defining “hot” versus “cold” tumors — an insight that transformed how immunotherapists understand tumor response. The conversation dives into how the tumor microenvironment, patient genetics and even the gut microbiome shape immune activity in cancer. His work continues to drive strategies to turn cold tumors into responsive ones, giving new hope to patients across all cancer types.  What You’ll Learn from Dr. Gajewsk Origins of the hot vs cold tumor concept and its impact on immunotherapy. How checkpoint inhibitors revive immune responses in T-cell–infiltrated (“hot”) tumors. Challenges of cold tumors and strategies to convert them into hot, immune-responsive tumors. Pioneering work linking the gut microbiome to immunotherapy response. The significance of interdisciplinary research, from tumor genetics to immunology.Humanizing science: the role of music and culture in building community and sustaining belief. Access more show notes, links and transcript here: https://www.moffitt.org/about-moffitt/podcasts/immunoverse/hot-vs-cold-tumors/

Dr. Patrick Hwu welcomes Dr. Elizabeth Jaffee of Johns Hopkins, a renowned leader in cancer immunotherapy. Dr. Jaffee shares the personal and scientific journey that led her to tackle one of oncology’s toughest challenges: pancreatic cancer. From her early fascination with virology to pioneering the use of genetically modified tumor vaccines, she has pushed the boundaries of what’s possible in cancer prevention and treatment. What You’ll Learn from Dr. Jaffee The role of KRAS mutations in early pancreatic cancer and how vaccines can target them How we can harness both targeted therapies and vaccines to overcome resistance in pancreatic cancer. How immunotherapy could be used for pancreatic cancer prevention The use of AI in early detection for at-risk patients Dr. Jaffee also discusses efforts to use immunotherapy earlier — even preventively — and explores how AI and multi-modal data could revolutionize cancer risk prediction and early detection. Key Takeaways KRAS vaccines are showing promise in preventing recurrence of pancreatic cancer post-surgery, with strong immune responses observed. Early pancreatic lesions already show immune reactivity, and vaccines may be able to activate these cells before cancer fully develops. Neoadjuvant immunotherapy—treatment before surgery—is producing encouraging immune responses in pancreatic cancer. AI and integrative data tools will be essential in identifying high-risk patients early and tailoring personalized prevention strategies. Mentorship is critical to the progress and future of cancer research. Access more show notes, links and transcript here: https://www.moffitt.org/about-moffitt/podcasts/immunoverse/targeting-kras/

Host Dr. Patrick Hwu sits down with immunotherapy pioneer Dr. James Mulé to discuss the origins and evolution of T cell therapies, groundbreaking discoveries at the NCI, and the translation of research to patient care at Moffitt Cancer Center.

Host Dr. Patrick Hwu sits down with trailblazing immunologist Dr. Phil Greenberg of Fred Hutchinson Cancer Center to explore how engineered T cells are revolutionizing cancer treatment. From early experiments in synthetic biology to today's clinical breakthroughs, Dr. Greenberg shares his decades-long journey to harness and rewire the immune system, turning obstacles into opportunities and transforming science fiction into standard of care.

In the premiere episode of The ImmunoVerse, host Dr. Patrick Hwu sits down with pioneering physician-scientist Dr. Steven A. Rosenberg, Chief of Surgery Branch at the National Cancer Institute. Together, they explore the roots of Dr. Rosenberg’s fascination with the immune system, tracing his remarkable journey from early scientific curiosity to the groundbreaking immunology discoveries that have reshaped cancer treatment.

Welcome to The ImmunoVerse™, a podcast exploring the past, present, and future of immunotherapy. In each episode, join Dr. Patrick Hwu as he sits with pioneering experts who are shaping the future of cancer treatment—uncovering breakthroughs, challenges, and the science driving this life-saving innovation. Don’t miss out—subscribe to The ImmunoVerse™ now and listen on your favorite podcast platforms!