Immunology & Immunotherapy Research

A collaborative study published in Science Advances reveals how the physical and metabolic conditions within the tumor microenvironment, particularly when combined with elevated blood sugar (hyperglycemia), enable cancer cells to form a thick, sugar-coated shield that hides them from immune surveillance. Led by Dr. Kevin Tharp at the Sanford Burnham Prebys Medical Discovery Institute, with key contributions from NFCR-supported scientist Dr. Valerie M. Weaver (UCSF) and co-investigators across North America, the research identifies a key stress-response protein, heat shock factor 1 (HSF1), as the driver behind this protective armor. What is the Glycocalyx and Why Does It Matter? The glycocalyx is a dense outer coating of sugar-derived molecules (glycoconjugates) that surrounds cells. In malignant tumors, cancer cells exploit this dense layer as a disguise, effectively hiding from T cells and other immune defenders. Key Discoveries from the Study Tissue Stiffness & Metabolism: Primary tumors are typically stiffer than surrounding healthy tissue. When cancer cells experience this physical pressure within the tumor microenvironment, their mitochondrial function and nutrient metabolism shift. The Role of Hyperglycemia: Under high-glucose conditions (hyperglycemia) modeled in human-like physiological media, cancer cells significantly thicken their glycocalyx shroud, dramatically increasing their ability to evade immune destruction. HSF1 as the Central Regulator: The researchers identified that the stress protein HSF1 regulates the synthesis and assembly of these sugar molecules. Hyperglycemia boosts immune evasion only when HSF1 is active in tumor-like microenvironments. Targeting HSF1 Restores Immune Surveillance: Inhibiting HSF1 prevents the thickening of the sugary shield, stripping away the disguise and enabling the immune system to recognize and destroy cancer cells. Why This Matters for Patients and Clinicians With the rising global incidence of type 2 diabetes and metabolic syndrome, high blood glucose has become a recognized risk factor for cancer progression and worse treatment outcomes. This study provides a biological mechanism connecting high blood sugar directly to tumor immune evasion. Overcoming Immunotherapy Resistance: Thinning the glycocalyx by targeting HSF1 or its downstream metabolic pathways presents a drug-discovery strategy to improve responses to checkpoint inhibitors and other immunotherapies. Targeting Metastatic Spread: Because HSF1 has also been linked to cancer invasion and metastasis, disabling this protective coat could make aggressive, migrating cancer cells vulnerable to immune clearance. NFCR Support in Action This breakthrough builds on long-standing research into the biomechanical forces and glycomics of the tumor microenvironment. The study was supported in part by the National Foundation for Cancer Research (NFCR), alongside the National Institutes of Health, the National Cancer Institute, the Canada Excellence Research Chair in Glycomics, and the Ovarian Cancer Research Alliance. Read More about the Tumor Microenvironment: Sign-up to Stay Informed About Cancer Research Breakthroughs with NFCR!

In a new episode of All Things Cancer, NFCR President and CEO Dr. Sujuan Ba interviews Dr. Monica Bertagnolli—former Director of both the National Cancer Institute and the National Institutes of Health. Their conversation touches on the state of U.S. cancer research, the challenges facing today’s scientific workforce, and how artificial intelligence may reshape patient care.   From Rural Roots to National Leadership Growing up on a Wyoming cattle ranch, Dr. Bertagnolli learned firsthand how limited access to healthcare affects rural communities. That experience continues to guide her commitment to equity and to ensuring that innovations in cancer research reach every patient, regardless of geography.   Protecting the Future of Cancer Science She expresses deep concern about unstable federal funding, noting its impact on labs, young scientists, and long-term discoveries. While there is bipartisan recognition of NIH’s importance, she stresses that philanthropy remains essential for sustaining cancer research during uncertain times.   AI in Medicine: Promise With Responsibility AI could dramatically improve diagnosis and treatment, but Dr. Bertagnolli underscores that these tools must be backed by strong evidence and real-world data from diverse populations. Above all, patients and clinicians must trust how AI is used. Sign-up to Be Informed When the Next Episode Comes Out! A Vision for Progress She envisions a system where patient data is protected, reliable, and used to drive better outcomes—ensuring that the future of cancer care is more equitable, innovative, and effective. About All Things Cancer Each episode of All Things Cancer will spotlight the most pressing topics in oncology, from cutting-edge treatments and emerging research to personal stories of resilience and hope. More than just a podcast, it’s a platform for raising awareness, advancing cancer education, and fostering a global community of support and collaboration. Hosted by NFCR CEO, Sujuan Ba, Ph.D., this compelling series will bring together the entire ecosystem of cancer research—including leading scientists, oncologists, doctors, patient advocates, caregivers, biotech innovators, and survivors—for powerful discussions on the breakthroughs shaping the future of cancer research, treatment, and care. All Things Cancer is now available on Spotify and Apple Podcasts, with new episodes released biweekly. Subscribe now to stay up to date on the latest episodes and join the conversation that’s shaping the future of cancer research. Cancer impacts everyone—whether you're a patient, caregiver, advocate, or researcher, this podcast delivers invaluable insights from those on the frontlines of the fight against it. {{ vc_btn: title=Spotify&color=success&size=lg&css=&link=url%3Ahttps%253A%252F%252Fopen.spotify.com%252Fshow%252F4TLBQLo8Lz2mkoIXd7CcDp%253Fsi%253DLCOo25W-QpCn6qO3M9WHAg%7Ctarget%3A_blank }}{{ vc_btn: title=Apple+Podcasts&color=purple&size=lg&css=&link=url%3Ahttps%253A%252F%252Fpodcasts.apple.com%252Fus%252Fpodcast%252Fall-things-cancer-national-foundation-for-cancer-research%252Fid1798723662 }}{{ vc_btn: title=YouTube&color=danger&size=lg&css=&link=url%3Ahttps%253A%252F%252Fwww.youtube.com%252Fplaylist%253Flist%253DPLTfVpaSmDvHw-r6FF_eAF0lCBriY_ldYC }} A world without cancer is possible. Help us turn lab breakthroughs into life-saving realities. 5.7 Million+ Donors who have fueled NFCR's mission $420 Million+ Invested in high-impact research & programs 36+ Labs & Hundreds of Nobel Laureates & Key Scientists received NFCR funding, driving breakthrough research {{ vc_btn: title=MAKE+THE+DIFFERENCE&style=outline-custom&outline_custom_color=%23FF5012&outline_custom_hover_background=%23FFFFFF&outline_custom_hover_text=%23002C76&align=center&link=url%3Ahttps%253A%252F%252Fdev.nfcr.org%252Fmake-the-difference%252F }}

 “What’s next for cancer research?” It’s a question that drives every scientist, clinician, and innovator in the NFCR network—and one that takes center stage in the newest episode of All Things Cancer, hosted by NFCR President and CEO Dr. Sujuan Ba. In this special conversation, two generations of cancer researchers come together to explore how far we’ve come—and how bold collaboration is shaping what’s next. From Chemotherapy to Cell Therapy: A 50-Year Journey For Dr. Brian Leyland-Jones, NFCR’s longtime medical advisor and one of the most respected oncologists in the field, the evolution of cancer care has been nothing short of extraordinary. “When I began treating patients,” he recalls, “we had nothing but chemotherapy. Today, I can sequence nearly every patient and tailor therapies based on the mutations driving their disease.” Throughout his decades-long partnership with NFCR, Dr. Leyland-Jones has witnessed the organization’s pivotal role in advancing early-stage discoveries—funding the kind of high-risk, high-reward science that traditional agencies often overlook. “NFCR funds the impossible dream,” he says, “supporting brilliant people and ideas that move the field forward.” A New Generation Pushing the Boundaries of Immunotherapy Representing the next wave of innovation is Dr. Avery Posey, an NFCR-supported scientist at the University of Pennsylvania whose laboratory is pioneering next-generation CAR-T cell therapies for solid tumors such as pancreatic cancer. While CAR-T therapy has already transformed treatment for certain blood cancers, its success in solid tumors has remained elusive. Dr. Posey’s research focuses on making these immune-cell therapies more precise, more durable, and less toxic—targeting cancer cells through changes in protein structures and carbohydrate signatures known as glycans. His work is helping redefine what’s possible in immunotherapy, offering hope that these breakthroughs could soon extend to millions of patients whose cancers are currently untreatable with CAR-T. Sign-up to Be Informed When the Next Episode Comes Out! Looking Ahead: CRISPR, Early Detection, and Collaboration Throughout their discussion, Drs. Posey and Leyland-Jones explore emerging frontiers—from CRISPR-based gene editing and RNA therapeutics to liquid biopsies and new strategies for early detection. They agree that the next decade will bring unprecedented progress—but only if researchers continue to collaborate across disciplines and generations. As Dr. Leyland-Jones notes, “We’re stronger when we work together. NFCR’s culture of partnership is what keeps innovation alive.” About All Things Cancer Each episode of All Things Cancer will spotlight the most pressing topics in oncology, from cutting-edge treatments and emerging research to personal stories of resilience and hope. More than just a podcast, it’s a platform for raising awareness, advancing cancer education, and fostering a global community of support and collaboration. Hosted by NFCR CEO, Sujuan Ba, Ph.D., this compelling series will bring together the entire ecosystem of cancer research—including leading scientists, oncologists, doctors, patient advocates, caregivers, biotech innovators, and survivors—for powerful discussions on the breakthroughs shaping the future of cancer research, treatment, and care. All Things Cancer is now available on Spotify and Apple Podcasts, with new episodes released biweekly. Subscribe now to stay up to date on the latest episodes and join the conversation that’s shaping the future of cancer research. Cancer impacts everyone—whether you're a patient, caregiver, advocate, or [...]