David Sancho
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sancholab.bsky.social
David Sancho
@sancholab.bsky.social
Passionate about #immunology. Sensing damaged self, infections & microbiota by DCs and macrophages to ignite innate & adaptive immunity. #Immunometabolism

Professor of Immunology @CNIC, Madrid, Spain. https://www.cnic.es/en/investigacion/immunobiology
📝 Study led by @annalaura-m.bsky.social & @iroblesv.bsky.social
🙏🏻collab #CNIC_CARDIO, #Borjaibanez1 starting this with me 7 years ago, Valentin Fuster, Fredrik Bäckhed on all ImP work, Göran Bergström IGT cohort, Kostas Stellos, Gabriel Nuñez Coral Barbas & many other col.
July 16, 2025 at 5:37 PM
🧪 ImP is a circulating biomarker of early and active #atherosclerosis, with diagnostic and therapeutic potential.
📉 Its effects are lipid-independent: ImP–I1R–mTOR axis in myeloid cells as a new therapeutic target for atherosclerosis. Synergy with lipid-lowering therapy?
#immunosky #cardiosky
July 16, 2025 at 5:37 PM
🧠 Mechanism: ImP acts through the imidazoline receptor I1R (Nischarin) in myeloid cells, activating mTOR and inducing TNF production.
🧬 Genetic or pharmacological blockade of I1R prevents #atherosclerosis development without lowering cholesterol.
#immunosky #cardiosky #microbiomesky
July 16, 2025 at 5:37 PM
🐭 In mice, oral ImP administration is sufficient to drive #atherosclerosis, without altering cholesterol or glucose.
🧪 It triggers #innate and #adaptive #immune activation and systemic inflammation.
#immunosky #cardiosky #microbiomesky
July 16, 2025 at 5:37 PM
In two independent human 🚶‍♀️🚶‍♂️cohorts (PESA @CNIC_CARDIO and IGT), plasma ImP levels were higher in people with subclinical #atherosclerosis, defined by multimodal advanced imaging (ultrasound, CT, PET-FDG). ImP linked to ACTIVE atherosclerosis in PESA.
#immunosky #cardiosky #microbiomesky
July 16, 2025 at 5:37 PM
🔬 Using #untargeted #metabolomics in #atherosclerosis-prone mice, we identified ImP as strongly associated with plaque formation, even in the absence of cholesterol changes.
🦠 ImP concentration depend on gut #microbiota composition.
#immunosky #cardiosky #microbiomesky
July 16, 2025 at 5:37 PM
🧩Conclusions:
✔️ cDC1s promote atherosclerosis via STING-driven IL-12 boost of Th1 & CD8+ T cell immunity
✔️ Targeted immunosuppression of cDC1s reduces inflammation and plaques
🧠 Novel precision strategy to tackle atherosclerosis beyond lipid control
#CardioImmunology #immunosky #cardiosky
June 22, 2025 at 5:42 PM
🧩 A step closer to immune-based therapies for CVD
Anti-CLEC9A-dexamethasone NPs:
⬇️ Th1 CD4+
⬇️ Cytotoxic CD8+
⏸️ No effect on Tregs or Th17
🦠 Preserve acute antiviral immunity (tested in influenza infection)
➡️ Specific immunomodulation of cDC1s without global immunosuppression!
#immunosky #cardiosky
June 22, 2025 at 5:42 PM
A new therapeutic tool:
Nanoparticles (NPs) decorated with anti-CLEC9A (cDC1-specific) and loaded with dexamethasone.
🎯 Target cDC1s with high specificity
📉 Reduce lesion size
🧾 No changes in lipid profile
🛡️ No toxicity to liver or kidneys
#NanoImmunotherapy #immunosky #cardiosky
June 22, 2025 at 5:42 PM
What activates cDC1s?
We found that STING signaling in cDC1s is required for their pro-atherogenic role.
STING-deficient cDC1s =
🧬 Fewer plaques
⬇️ CD4+ Th1 and CD8+ IFN-γ+ T cells
🧠 STING is a crucial upstream driver in cDC1-mediated inflammation
#immunosky #cardiosky
June 22, 2025 at 5:42 PM
scRNA-seq of aortic CD3+ T cells shows:
⬇️ Th1 and CD8+ IFN-γ+ T cells in the absence of cDC1s
⬇️ IL-12 expression
🧬 ↓ T cell clonality in CD4+ Th1 and CD8+ cytotoxic subsets
💡 cDC1s fuel local and systemic pro-inflammatory T cell responses
#immunosky #cardiosky
June 22, 2025 at 5:42 PM
Even without FLT3L, selective depletion of cDC1s reduces plaque formation upon HCD feeding in two models: Xcr1-DTA OR Irf8Δ32 BM graft in Ldlr⁻/⁻
Fewer CD3+ T cells in aorta
No changes in cholesterol-body weight
➡️ cDC1s promote atherogenesis independent of lipid metabolism
#immunosky #cardiosky
June 22, 2025 at 5:42 PM
DC expansion with FLT3L (mFLex) in Ldlr⁻/⁻ mice on high-cholesterol diet (HCD)
➡️ increased atherosclerosis. This effect disappears when cDC1s are depleted (Xcr1Cre-DTA BM graft in Ldlr⁻/⁻ mice).
➡️cDC1s are required for lesion expansion upon FLT3L administration.
#ImmunoCardio #immunosky #cardiosky
June 22, 2025 at 5:42 PM
🧬 New immunotherapy for atherosclerosis @ahajournals.bsky.social #CircRes
Type 1 dendritic cells (cDC1s) promote atherogenic immunity & can be targeted with tolerogenic nanoparticles.
🔗 doi.org/10.1161/CIRC...
#Immunotherapy #Atherosclerosis #Nanomedicine
#CNIC_CARDIO #immunosky #cardiosky
June 22, 2025 at 5:42 PM
Congrats Irene Adán-Barrientos: great thesis presentation & defense at CNIC & @uam.es

Thx thesis commitee: Julián Aragonés, Arantxa Cruz-Adalia & Bart Everts on wonderful discussion and visit!

Thx Gillian Dunphy @gilliandunphy.bsky.social on fantastic co-supervision!!!
June 17, 2025 at 1:30 PM
Intratumoral presence of CD4+ Trm correlates with cDC1 abundance and patient #survival in #breast carcinoma (BRCA) & skin #melanoma (SKCM).
#immunosky #cancersky (6/7)
April 15, 2025 at 6:05 PM
#Neoadjuvant cDC1-based vaccination enhances CD8+ and CD4+ memory T cell responses upon tumor recurrence. cDC1 immunotherapy triggers a CD4+ Trm subset as the key subset increased and associated also to augmented CD8+ T cell cytotoxic response.
#immunosky #cancersky (5/7)
April 15, 2025 at 6:05 PM
Both in the #adjuvant (cDC1 treatment after tumor resection) and particularly in the #neoadjuvant (cDC1 vaccine while the tumor is still present) setting, cDC1 vaccines are highly effective in preventing cancer #recurrence after primary tumor resection.
#immunosky #cancersky (4/7)
April 15, 2025 at 6:05 PM
cDC1 #tumor #vaccines are superior in induction of anti-cancer T cell memory compared with cDC2 vaccines. cDC1 vaccines are thus more effective in prophylactic anti-cancer vaccination.
#immunosky #cancersky (3/7)
April 15, 2025 at 6:05 PM
cDC #immunotherapy is prepared with #tumor cell lysate (TCL) from a tumor (e.g. MC38) & activated with CpG (optimal adjuvant). cDC1s are better at Th1 & cDC2s at Th17 induction. In vivo, cDC1s vaccines are better than cDC2-based ones for therapy of MC38 & B16-OVA tumors.
#immunosky #cancersky (2/7)
April 15, 2025 at 6:05 PM
#immunosky #epw2025 Fantastic presentation by Steffi Wculek @irbbarcelona.org showing on how #macrophages use OXPHOS for lipid processing (enclosed publication). New data on cDC1s regulating their immunogenicity through metabolite regulation by OXPHOS balance. www.sciencedirect.com/science/arti...
March 26, 2025 at 2:29 PM
#immunosky #epw2025 Great novel work by @masslab.bsky.social on the impact of micro and nanoplastics in macrophages! Large effect on liver Kupffer cells, while other organs are more protected. Read more here!!!
sciety.org/articles/act...
March 26, 2025 at 1:56 PM
#immunosky #epw2025 Fantastic meeting starting! Thx to the wonderful co-organizers @mcasanova.bsky.social & @silvestreroiglab.bsky.social
Thx to support by #SEI (Spanish society for immunology), Inmunotek @miltenyibiotec.bsky.social @embo.org @efis-immunology.bsky.social @eurjimmunol.bsky.social
March 26, 2025 at 1:45 PM