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.

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

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

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.

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.