How do we make immunotherapy work better in HNSCC? At #AACR26, I’m presenting our work showing "LSD1 inhibition reprograms the tumor microenvironment and enhances anti-PD-1 response." 🔬 Great discussions, sharp questions, and inspiring science all around. @AACR #CancerResearch #Immunotherapy #HNSCC #TumorImmunology #Epigenetics #CheckpointBlockade #CancerBiology #TranslationalResearch #OralCancer

🧠 The first immunocompetent H3 G34R pediatric brain tumor model shows a decisive outcome: dendritic cell vaccination with whole tumor lysate anti–PD-1 achieves durable survival, while 100% of controls die. The G34R mutation itself is not a demonstrated neoantigen. The dendritic cells identified targets bioinformatics could not predict. 🔬 Whole lysate. Competent instructor. The immune system executes. 📊 In the DCVax-L Phase III trial, a single product yielded: 25,109 MHC-I peptides 12,940 MHC-II peptides No preselection. Full antigenic breadth. ⚡ G34R impairs DNA repair and primes cGAS–STING, aligning with proton radiation biology: sustained immune activation without early shutdown. 🏥 UCLA Health has opened the first clinical trial for this tumor type (NCT06342908), using DC vaccination with poly-ICLC. Same research group. Same platform. Now in humans. 🎯 Three failure layers exposed: 🧬 IL-12 variance → infiltration without cytotoxic execution 🧱 Periostin ECM barrier → structured immune exclusion ⏱️ Sequence error → macrophage exhaustion trap 💡 The failure in cancer immunotherapy is not the effector cell. It is the instruction layer. Sequence is the mechanism. The instructor determines the outcome. 🔑 $NWBO #DCVax #DendriticCells #H3G34R #PediatricBrainTumor #Immunotherapy #GBM #ProtonTherapy #IL12 #CancerResearch #Neurooncology #WholeTumorLysate #CheckpointBlockade #PrecisionMedicine #cGASSTING #PediatricCancer #BrainTumor #CellTherapy #ImmuneInstruction #DCVaccine #NCT06342908

#ScienceSaturday ❓ Why do some cancers resist anti-PD-1 immunotherapy? ➡️ A new study in @Nature shows that cancer-induced nerve injury (CINI) drives resistance. Tumors that damage nearby nerves trigger chronic inflammation, creating an immune-suppressive environment that blunts checkpoint blockade. ➡️ Importantly, targeting nerve injury pathways — such as blocking IL-6 signaling — helped restore response in models, pointing to new strategies to overcome resistance. 🌟 Congratulations to co-corresponding author Dr. Ken Tsai (@KYTsaiLab) of @MoffittNews, collaborators @MDAndersonNews and others for advancing this critical field. 🔗 Read more: doi.org/10.1038/s41586-025-0… #CancerResearch #Immunotherapy #CheckpointBlockade #Neuroimmunology

#ScienceSaturday ❓ Why do some patients respond better to immunotherapy? ➡️ A new study in Nature found that tumors with mutations in PPP2R1A — a gene encoding a scaffold protein in the PP2A complex — were linked to much longer survival after immune checkpoint blockade (ICB). ➡️ In ovarian clear cell carcinoma and other cancers, PPP2R1A mutations were tied to stronger immune signals, more tumor-infiltrating T cells, and better tumor control. Preclinical models confirmed that altering or inhibiting PPP2R1A boosted the effectiveness of ICB and CAR-T therapies. 🌟 These findings suggest PPP2R1A mutations could serve as a predictive biomarker for immunotherapy success and highlight PP2A as a potential therapeutic target to make treatments more effective. 🔗 Read more in @Nature: doi.org/10.1038/s41586-025-0… @NaturePortfolio @MDAndersonNews #CancerResearch #Immunotherapy #Biomarkers #OvarianCancer #CheckpointBlockade Thank you, @AmirJazaeri for your visit and lecture @MoffittNews this week!

Translation dysregulation may serve as a new source for identifying cancer-associated antigens, and may also help to predict responses to checkpoint blockade bit.ly/3E4OMY8  @chen_weller  @samuels_yardena @Samuels_lab #CheckpointBlockade #CancerImmunotherapy

(4/6) Most interestingly- 🔬 RNA STEP analysis shows upregulation of DNA-damage-related genes & immune markers (T cells, B cells, macrophages) post-lurbinectedin treatment in pre- vs post-lurbinectedin treated SCLC clinical samples. 💥 MHC-I/II & PD-L1 gene expression increased, enhancing immune recognition of tumors. 🖼️ Multiplex immunofluorescence confirms more CD8 T cells infiltrating lung tumors & CD19 /CD138 antigen-presenting cells. Lymph nodes of treated patients show: ✅More cytotoxic CD8 T cells in metastases (liver & lymph nodes) ✅Higher 4-1BB T cells → stronger co-stimulatory response ✅Increased antigen-presenting cells (CD19 /CD138 ) in tumor stroma #CancerImmunotherapy #STINGPathway #LungCancerAwareness #PrecisionMedicine #LungCancer #Immunotherapy #CancerBiology #CheckpointBlockade #OncologyResearch #SCLCAdvancements #CheckpointInhibitors #ImmunoOncology #TumorMicroenvironment

(3/6)🧬 Our study reveals : ✅ Lurbinectedin activates the STING-IFN pathway, a critical immune surveillance system that boosts interferon signaling and alerts the immune system to the presence of tumors. ✅ It increases MHC-I expression, making cancer cells more visible to immune cells. ✅ It enhances CD8 T cell infiltration, ensuring that more cancer-fighting immune cells reach the tumor site. ✅ It shifts macrophages from an immunosuppressive (M2) state to a pro-inflammatory (M1) state, further supporting a more active anti-tumor immune response. In short, lurbinectedin "primes" SCLC tumors to respond to immunotherapy, helping checkpoint inhibitors like atezolizumab and pembrolizumab work more effectively. For SCLC patients, this could mean more durable responses and new therapeutic possibilities. #TumorImmunology #CancerBiology #CheckpointBlockade #STINGActivation #ImmunoOncology #PrecisionMedicine

New research reveals how tumors resist #CheckpointBlockade and immune-stimulatory combination therapies—and shows that blocking the recruitment of PMN-MDSCs can sensitize these tumors in mice. @NccriOfficial scim.ag/41fOGpd

Multiomics & spatial mapping of tumor samples from patients with advanced #RenalCellCarcinoma, as well as integration of transcriptomic and HLA genotyping data provides a machine learning-derived signature of response to #immune #CheckpointBlockade. nature.com/articles/s41591-0…

🔐 The key to predicting #CheckpointBlockade responses in #melanoma? This important study from @NatalieEdner et al. @LucyWalkerlab identifies #Tcell markers that could indicate patient response to #PD1 blockade before treatment #OpenAccess ➡️bit.ly/3MAtROH

Multiomics & spatial mapping of tumor samples from patients with advanced #RenalCellCarcinoma, as well as integration of transcriptomic and HLA genotyping data provides a machine learning-derived signature of response to #immune #CheckpointBlockade. nature.com/articles/s41591-0…

Blocking WNT/b-catenin pathway in #NSCLC with a high tumor mutational burden helped overcome resistance to #CheckpointBlockade therapy in mice. Read the research from 2021: scim.ag/5KP #WeekendReads

On #WorldCancerDay we’re proud to showcase our best recent #cancer research in this joint Virtual Issue with our sibling journals @CEIjournal & @discovimmunol ✨ Enjoy cutting-edge research covering DC-targeting lentivectors, #CheckpointBlockade & #irAEs: bit.ly/48LWuAx

Last chance to sign on to this #CheckpointBlockade therapy #training course! ⏰ Fit essential #cancer #immunotherapy learning around your schedule with interactive online content curated by academics & clinicians 💻 Sign up by tomorrow 👉bit.ly/3s1ifMz

Get up to speed with immune #CheckpointBlockade therapy in this self-guided online #training ⏩ Open the doors to... ✅ Empowered decision-making ✅ Productive conversations with patients, colleagues or clients ✅ Enhanced #career opportunities Sign up 🔗bit.ly/3s1ifMz

#Training course: #CheckpointBlockade therapy 💻 Self-paced e-learning – fit around your schedule 🧬 Science underpinning therapeutic responses 🗣️ Hear from clinicians & patients 🔬 Focus on #melanoma, lung & colorectal #cancers Sign up by 2 Feb! bit.ly/3s1ifMz

Ready to transform your knowledge of #cancer #immunotherapy? Uncover the science, impact & future developments of #CheckpointBlockade therapy in this online #training course curated by experts 🩺 Enrol before 2 February: bit.ly/3s1ifMz

Kick off the New Year with a deeper insight into #cancer treatment 💥 This course will transform your understanding of #CheckpointBlockade therapy with interactive content curated by academics & clinicians Broaden your horizons in 2024 👉bit.ly/3s1ifMz

#Training course: #CheckpointBlockade therapy 💻 Self-paced e-learning – fit around your schedule 🧬 Science underpinning therapeutic responses 🗣️ Hear from clinicians & patients 🔬 Focus on #melanoma, lung & colorectal #cancers Find out more & sign up: bit.ly/3s1ifMz

#Training opp: discover how #CheckpointBlockade has unlocked the potential of the #ImmuneSystem in the treatment of #cancer 🎯 🔸Featuring interviews with clinicians & patients 🔸From basic science principles to the impact in the #clinic All online 🔗bit.ly/3s1ifMz