Immunology Research Insights

Triple-negative breast cancer (TNBC) is one of the most aggressive breast cancer subtypes. It lacks the three receptors (ER/PR/HER2) that enable targeted therapies in other forms of breast cancer and recurs early (often peaking ~3 years after diagnosis). Its genomic instability and immunogenic microenvironment make it a strong candidate for individualized immunotherapy. In a Phase 1 clinical trial led by Prof. Dr. med. Marcus Schmidt and investigators from Germany and Sweden, just published in Nature, we evaluated an individualized neoantigen mRNA vaccine approach in 14 patients with early-stage TNBC after surgery and (neo)adjuvant therapy. Each vaccine encoded up to 20 patient-specific neoantigens on two mRNA molecules, delivered intravenously via lipid nanoparticles to target dendritic cells. The results showed robust immune responses: • All patients in the clinical trial developed vaccine-induced T cell responses against multiple neoantigens. • Vaccine-induced CD8⁺ T cells reached frequencies commonly achieved with adoptive T cell therapies and persisted functionally for years without boosters – evolving into both "ready-to-act" cytotoxic effector cells and stem-like memory T cells. • 11 of 14 patients remained relapse-free for up to six years post-vaccination. Furthermore, the findings in three patients with relapses were instructive for potential future combination treatment strategies to overcome resistance – each revealing a distinct escape mechanism to be addressed: • Enhancing response magnitude: The patient with the weakest vaccine-induced response relapsed but achieved complete remission on subsequent anti–PD-1, suggesting a response threshold and supporting combination strategies. • Targeting antigen-presentation loss: One patient showed near-complete loss of MHC class I (likely via B2M downregulation), despite vaccine-induced T cells being present, highlighting the need to address HLA-loss escape (e.g., antibodies or strategies restoring recognition). • Comprehensive tumor sequencing: In another patient the relapse originated from a contralateral, genetically independent tumor not covered by the vaccine design, underscoring the importance of sequencing multiple lesions in hereditary settings. Overall, these results demonstrate feasibility and durable neoantigen-specific immunity in TNBC supporting personalized mRNA cancer vaccines as platform technology, while pointing to novel treatment strategies to overcome resistance – especially through informed treatment combinations. 𝐋𝐢𝐧𝐤 𝐭𝐨 𝐩𝐮𝐛𝐥𝐢𝐜𝐚𝐭𝐢𝐨𝐧: https://lnkd.in/dk4fq6nA #CancerResearch #Oncology

Stanford scientists have discovered that cancer cells don’t just use one trick to hide from the immune system—they use two separate “don’t-eat-me” signals to stop macrophages from killing them. The first signal, CD47, was already famous for acting like an invisibility cloak that tells macrophages to back off, and blocking it with an anti-CD47 antibody is already in human trials. In the Nature Immunology paper, the same Stanford team also found that tumors use MHC class I as a second stop signal by binding to a macrophage receptor called LILRB1, which suppresses the macrophage’s ability to engulf and destroy the cancer. When researchers blocked both CD47 and LILRB1 in mice, tumors rapidly filled with immune cells, shrank significantly, and became far easier for the body to clear. This shows that many cancers survive by running two overlapping escape systems, and turning off both “don’t-eat-me” pathways at once may dramatically boost the immune system’s ability to attack and eliminate tumors.

BREAKING: US health officials are likely to adopt Denmark’s vaccine schedule. Take it from this pediatrician: This is bad public health. It misses critical context and will confuse families. The stated rationale is that Denmark "gives fewer vaccines". This comparison leaves out why their schedule looks different. Denmark vaccinates against 7 fewer diseases, largely due to cost considerations -- not because vaccines are unsafe or unnecessary. Take RSV as one example. In the US, we vaccinate babies against RSV, the leading cause of hospitalization for infants. We also vaccinate against chickenpox (varicella), which can be serious in young children -- and what's more, vaccination helps prevent shingles later in life. These decisions reflect the real burden of disease we see here in the US, and the decisions we've made to prevent these illnesses. Vaccine schedules are built on country-specific data. Denmark has 6 million people and a much smaller geographic footprint (roughly the size of Maryland). The US has 56 times as many people and is far bigger geographically. Controlling outbreaks in the US is challenging, making prevention through vaccination especially important. There’s also a major systems difference: Denmark has universal healthcare. In the US, many families delay or avoid care due to insurance barriers. When we give vaccines, we help prevent serious illness before families ever face these obstacles. (I wish we had health care for everyone, but the fact is, we don't, and preventing devastating hospitalizations -- both medically and financially devastating -- is critical.) As a pediatrician and a dad, I know shots can be stressful for some families. But our vaccine schedule is carefully designed to give the fewest shots, at the right times, to prevent the greatest harm. Talk with your pediatrician. We’re here to help families make sense of this. Thanks to WCVB Channel 5 for having me on to discuss. Full clip here: https://lnkd.in/eWDyMCjU CC: American Academy of Pediatrics #pediatrics #publichealth #vaccines #prevention #childhealth #cdc

Your dendritic cells have a bedtime, and it might be rewriting how we design vaccines. A new Science Advances paper just showed that the exact same vaccine, given to the exact same mice, produces two different flavors of memory CD8+ T cells depending on the clock. Not more or fewer cells. A different kind of cell entirely: battle-ready effectors at one hour, long-lived stem-like progenitors at another. The dial turns out to be a single dendritic cell protein, CD70, ticking on a 24-hour loop. It's an elegant mechanism, five knockout models deep. But it also lands in a field that already has three other "the clock controls this" papers, each pointing to a different molecule and a different optimal hour. So is chronoimmunology closing in on a real answer, or just generating an ever-more-detailed catalog of contradictions? I dug into the paper, and the wider literature, to find out.

#Nature Aging: Men and women age very differently—at the immune system level A massive single-cell study (1M+ immune cells, ages 19–97) just revealed something striking: Immune aging is not the same for men and women—and it may explain major disease differences later in life. Key takeaways: 🔹 Women: stronger—but riskier—immune aging - More dramatic immune remodeling over time - Expansion of highly cytotoxic T cells - Increased chronic inflammation (“inflammaging”) - Sharp rise in autoimmune risk (especially after menopause) ➡️ This may explain why ~80% of autoimmune diseases occur in women. 🔹 Men: quieter—but more dangerous—changes - Subtle immune shifts, especially in B cells - Clonal expansion of CD5+ B cells (a known pre-cancer state) - Higher susceptibility to blood cancers like CLL - Greater vulnerability to chronic infections ➡️ Immune aging in men may “hide” risk until disease emerges. Big picture: This study challenges the long-standing “one-size-fits-all” view of immune aging. 🔹 Women trend toward autoimmunity & inflammation 🔹 Men trend toward clonal expansion & cancer risk Why it matters: - Precision medicine must consider sex-specific immune trajectories - Aging research needs to move beyond averaged populations - Prevention strategies may need to diverge by sex 💡 The immune system doesn’t just weaken with age—it diverges. #Immunology #Aging #PrecisionMedicine #AutoimmuneDisease #CancerResearch #SingleCell #NatureAging

Yale University just cracked one of CAR-T’s biggest limitations. Most FDA-approved CAR-Ts struggle when tumors don’t wave enough “cancer flags.” Low-antigen cancers slip through. But Yale researchers may have found a fix: Intrinsically Disordered Regions (IDRs). - In culture dishes, IDR-CAR-Ts showed far stronger killing activity, even against cells with low CD19, CD22, or HER2. - In mouse models, FUS-IDR CAR-Ts suppressed both blood cancers and low-HER2 colorectal tumors, with reduced exhaustion markers (PD1, LAG3). - IDRs are found in ~50% of human proteins - an untapped toolkit for immune engineering. Why it matters: CAR-T’s problem has never been promise - it’s persistence. If this approach holds, we’re talking broader reach, longer durability, and a new modular playbook for solid tumors. Every biotech working in immunotherapy should be watching Yale. The door to low-antigen cancers might finally be opening.

10.2 billion healthy years of life Recent announcements in the United States to reduce recommended childhood vaccinations raise serious concerns. At a time of growing mistrust in science, stepping away from decades of robust evidence weakens public health systems and increases the risk of the return of vaccine-preventable diseases. This context underscores how essential it is to uphold a scientific voice that is evidence-based, independent, and fully engaged in the public debate. It was in this spirit that I had the honor of speaking yesterday as part of the William E. Paul Lecture at The National Institutes of Health. Bill Paul was a giant of immunology at the National Institute of Health , whose leadership was central to the creation of the Vaccine Research Center at the NIH. This lecture discussed new vaccine strategies and was an opportunity to reaffirm a fundamental truth: vaccines are among the safest, most effective, and most powerful public health tools ever developed. At a moment when vaccine research in the United States is being weakened, and when vaccination coverage against life-threatening diseases such as measles is declining, this message could not be more urgent. As a result of 50 years of vaccination, a child born today has a 40% increase in survival for each year of infancy and childhood. Considering the added benefit of reduced morbidity, 10.2 billion healthy years of life have been gained due to vaccination (Lancet Vol 403, 2024) We need a clear and collective reminder of how much vaccines have done for humanity and a renewed commitment to protect and strengthen the research that makes them possible. This research is essential for those still urgently needed to confront emerging diseases and persistent infectious threats for which humanity remains unprotected. Now more than ever, science must remain central to our societies and continue to guide collective decision-making. https://lnkd.in/eUXACmaW #Vaccines #PublicHealth #Science #NIH #GlobalHealth #VaccineResearch

Gut bacterium may be helping breast tumors hide from the immune system. And it appears to do it through a metabolite. Researchers found that Enterocloster bolteae, a member of the Lachnospiraceae family, became progressively more abundant as breast tumors developed. Its rise was linked to higher levels of deoxycholic acid, a secondary bile acid produced through microbial metabolism. But the metabolite did not remain confined to the gut. Deoxycholic acid accumulated inside the tumors and activated the farnesoid X receptor, or FXR, in cancer cells. That activation triggered NF-κB signaling and increased production of interleukin-6. IL-6 then recruited immune cells that can suppress antitumor immunity, including granulocytic myeloid-derived suppressor cells and T helper 17 cells. The result was a tumor microenvironment that appeared more capable of protecting the cancer from immune attack. The pathway looked like this: Enterocloster bolteae → deoxycholic acid → tumor FXR activation → NF-κB signaling → IL-6 production → immunosuppressive immune-cell recruitment → breast cancer progression This is more than another study showing that cancer is “associated” with changes in the microbiome. It proposes a specific biological chain connecting a gut organism, a circulating microbial metabolite, a receptor inside the tumor and a measurable immune response. Even more importantly, blocking FXR or IL-6 signaling weakened these effects in the experimental models. That creates several potential intervention points. Not just the bacterium itself, but its metabolic output, the tumor receptor it activates and the downstream inflammatory signal. This does not mean that modifying the microbiome can currently prevent or treat breast cancer. But it strengthens a much bigger idea: The gut microbiome may influence cancer progression from a distance by producing molecules that reach the tumor and reshape its immune environment. The next generation of cancer therapeutics may not focus only on the tumor. It may also target the microbial chemistry helping the tumor survive.

Family physicians know the truth: vaccines work. We’ve seen firsthand how they save lives, protect communities and keep families healthy. But if the public loses confidence in science, those protections weaken. We, as a country, cannot afford to let politics chip away at these foundations of public health. The testimony provided by career CDC employees at the HELP Committee hearing was deeply concerning. It is clear that trust in science and our public health infrastructure is eroding at an alarming pace. Public health systems that families rely on are being disrupted, and institutions once seen as trusted are being unduly influenced by political bias versus scientific facts and evidence. That should alarm every one of us.   We need honesty and accountability from our health care leaders. Our public health system and vaccine policy must be grounded in science and evidence, transparent, pursued with a universal commitment to facts, not politics. Anything less risks the health of the people we serve.   Family physicians are proud to stand on the front lines of prevention. They are highly trusted by their patients and the communities they serve. They do this hard work every single day, and see what’s possible when science leads the way. To continue to make this a reality, we must restore public trust and insist that science—not ideology—guides our path forward. That is the only way to a healthier, stronger future for our patients and our communities.

🧬 Vaccines: Ask the Doctor — The Truth Behind the Confusion and Controversy Grateful to have joined Fox32 Chicago and Sylvia Perez to address the growing confusion around vaccines—and why this moment matters more than ever. 💡 Bottom line: Vaccines are safe, effective, and grounded in decades of rigorous scientific research. But in recent months, we’ve seen changing guidance—especially from the ACIP (Advisory Committee on Immunization Practices)—lead to confusion, fear, and mistrust. While evolving science is a good thing, recommendations should always be made based on objective evidence, not politics or personal beliefs. When political narratives interfere with science, we all lose. 🔍 These are not decisions made lightly. Vaccine schedules have been studied for decades, across millions of patients, through independent, peer-reviewed research conducted by scientists, physicians, and public health experts worldwide. The claim that children receive “too many vaccines” or that we need to study the “cumulative effect” has been addressed time and again—there is no credible evidence that receiving multiple vaccines as scheduled is harmful. In fact, spreading them out or skipping doses can leave children vulnerable during critical windows. 🛡️ Herd immunity matters. We had once eradicated diseases like measles in the U.S.—a disease that can lead to severe complications or death in young children. That protection was only possible because of high vaccination rates across communities. But as coverage drops, outbreaks are already returning. We must not lose sight of how far we’ve come—and what’s at stake if we roll back trust and coverage. 🧾 And let’s be clear: uncertainty in guidance could impact insurance coverage. If recommendations aren’t clear or unified, insurers may stop covering life-saving vaccines. That puts low-income families at risk, widens health disparities, and reverses decades of progress in preventive care. Vaccines aren’t just about individuals—they’re about protecting entire communities. Preventing disease means keeping people out of the hospital. Preventing illness means protecting children, seniors, pregnant people, and those who are immunocompromised. Vaccines do that. 💬 This is why trusted communication matters. It’s not just about the science—it’s about making sure people understand it, trust it, and know that decisions are being made in their best interest. That’s what I strive to do as a physician, communicator, and advocate. 📺 Watch the full segment here: https://lnkd.in/gpTTkTpe ✅ If you’re looking for clear, unbiased, science-backed vaccine guidance, follow the American Academy of Pediatrics—they continue to maintain evidence-based recommendations that prioritize children's health. Public health is only as strong as the trust we build to support it. The University of Illinois Cancer Center Women in Medicine®