AACR Immunotherapy in Cancer: Balancing Efficacy and Autoimmune Toxicities - Melissa Lechner, MD

Join 17,000 Oncology Professionals Sign up for our e-newsletter: https://oncologytube.com/newsletter/

Show your passion for cancer research—grab exclusive oncology-inspired T-shirts at https://oncologytube.com/product/cancer-warrior-t-shirt/

ARTICLE: https://oncologytube.com/immunotherapy-side-effects-under-scrutiny-new-data-on-bone-density-and-t-cell-insights/

Join us for an in-depth exploration of the latest breakthroughs in cancer immunotherapy, straight from a cutting-edge expert session held on March 10, 2025! This video unpacks the complex challenge of autoimmune side effects tied to checkpoint inhibitors, a pressing issue now impacting roughly two-thirds of patients as immunotherapy expands beyond advanced cancers like stage IV melanoma into earlier stages. We’ll dive into groundbreaking research on predictive T-cell signatures—like IL-17-producing Th17 cells and IFN-γ-secreting CD8+ cells—that could revolutionize how we identify at-risk patients. You’ll hear about innovative therapeutic strategies, including IL-6 blockers like tocilizumab and JAK inhibitors, offering hope for managing toxicities that resist traditional steroids. Plus, a surprising twist: new data linking anti-PD-1 therapy to bone density loss, with implications for breast cancer patients and beyond. Featuring insights from top institutions like MD Anderson Cancer Center and the Crick Center in London, this discussion is packed with actionable findings for researchers, clinicians, and oncology enthusiasts. Want to stay ahead in oncology? Subscribe to our channel and hit play to advance the fight against cancer together!
10 Timestamps from the Transcript (No Bullets):
00:00:00 - "Introduction to Immunotherapy and Autoimmune Effects"
The speaker kicks off by introducing the session’s focus: immunotherapy’s growing use and its autoimmune side effects on healthy tissues. From the transcript: "we had today was talking about immunotherapy and the auto immune side effects that it can cause unhealthy tissues."

00:00:17 - "Prevalence of Side Effects"
Highlights that approximately two-thirds of patients experience autoimmune toxicities, a key reminder as immunotherapy expands. From the transcript: "side effects, which happen in about two/3s of patients."

00:00:27 - "Risk-Benefit in Stage IV Melanoma vs. Early Stages"
Discusses how tolerance for side effects differs between stage IV melanoma and earlier-stage cancers. From the transcript: "treating patients with stage four melanoma, I think the tolerance form of these side effects was different."

00:00:37 - "Predicting Toxicity Risk"
Introduces the session’s core question: Can we identify patients more likely to develop toxicities? From the transcript: "can we identify who might be more likely to get these side effects."

00:01:14 - "Th17 Cells and Colitis (MD Anderson)"
Dr. Demetrio from MD Anderson shares a T-helper cell profile (IL-17) linked to checkpoint inhibitor colitis, treatable with IL-6 blockers. From the transcript: "profile of tea helper cells that make underl Lucan 17 that was associated with both the development of Czewin inhibitor collitus."

00:01:38 - "Broad Profiling Approach (Crick Center)"
Dr. Max Emerick’s work at the Crick Center uses detailed baseline and on-therapy profiling to spot immune cell changes. From the transcript: "the crick center in London with Dr. Max Emerick that showed that by using sort of a broad approach."

00:02:06 - "Baseline Data for Predictive Signatures"
Stresses the need for genetic profiles (HLA, SNPs) and blood analysis to predict toxicities. From the transcript: "data set baseline. so that would involve genetic profiles like HLA type, thinking about duringline snips."

00:02:40 - "Tertiary Lymphoid Structures and Toxicity"
Links T-follicular helper cells and TLS to higher toxicity risk, citing John Wherry’s research. From the transcript: "form what's called a tertiate lymphoid structure... you’re much more likely to get these ottomian toxicities."

00:03:22 - "Surprising Bone Density Finding"
Dr. Gwendolyn Joseph reveals anti-PD-1 therapy reduces bone density in animal models, raising concerns for breast cancer patients. From the transcript: "there was actually a decrease in bone mineral density in some animal models where they were treating with antiPD1 therapy."

00:05:04 - "Janus Kinase Inhibitors as Alternatives"
Suggests JAK inhibitors and IL-6 blockers as non-steroidal options for steroid-resistant toxicities, aligning with new guidelines. From the transcript: "Janus Kinus inhibitors, so a lot of the work that was presented today did identify T cells and signaling through stats."