New preprint alert! 🚨
High-fat diet imprints a macrophage-tumor CAMP-P2RX7 axis driving pancreatic cancer initiation, plasticity and metastasis
www.biorxiv.org/content/10.6...
Together, the study reveals a macrophage-tumor cell circuit shaped by diet that fuels transformation, plasticity, and metastasis. Targeting this CAMP-P2RX7 axis could open new therapeutic avenues for obesity‑associated PDAC.
Additionally, in PDAC patients with higher BMI, we showed a conserved upregulation of CAMP, P2RX7 and CXCR4, even if they later lost weight due to disease. Obesity leaves a lasting molecular imprint on tumors.
These HFD‑induced tumors were also more metastatic. Their enhanced aggressiveness was intrinsic to the tumor cells, which also overexpress CXCR4. We also found that this not dependent on the host environment.
Mechanism? Fatty‑acid-educated macrophages secreted the antimicrobial peptide CAMP, which activated P2RX7 signaling in tumor cells. This pushed cells into a highly plastic, immune‑evasive state reinforced by PGLYRP1, which shields them from phagocytosis.
HFD‑driven tumors adopted a distinct, aggressive identity: more mesenchymal, more plastic, and enriched in stem‑like features. This phenotype persisted even in tumor‑derived cell lines, pointing to a stable, diet‑imprinted state.
Strikingly, in the late adulthood onset that is normally resistant to KRAS/TP53‑driven transformation, mice developed full PDAC when exposed to HFD. Diet alone didn’t cause tumors in healthy mice, but in the presence of oncogenic mutations, it became an accelerator.
Here we uncover how HFD doesn’t just increase pancreatic cancer risk, it actively rewires the tumor ecosystem. Using an adult PDAC mouse model and early and late adulthood protocols, we show that HFD accelerates tumor initiation and worsens outcomes.
Usually it is said that EMT and stemness are coupled mechanisms and for some authors, more EMT = more stemness but NO. EMT and stemness are parallel programs in some cases but independent. This article gives more insights into this:
www.cell.com/iscience/ful...
Your periodic reminder that science is not done by a few selected "stars scientists". Science is done by hundred of thousands. Siloed money mean a few flashy discoveries and a lot of waste. Want to change things? Make funding accessible and stop funding calls with less than 2% success rate.
Los últimos avances en la investigación del cáncer de páncreas, en un congreso de la @fundacionareces.bsky.social coordinado por Mariano Barbacid y Carmen Guerra, con Francisco X. Real, Núria Malats y Vasiliki Liaki, de #CNIOStopCancer.
🔏Inscripciones gratis online t.co/IRqqi8XfFR
El @csic.es difunde la concesión de la ayuda de proyectos sinérgicos de la Comunidad de Madrid a nuestro compañero Dr. Bruno Sainz junto con el Dr. Sergio Serrano-Villar @serranovillar.bsky.social del #IRYCIS
Enhorabuena a los dos grupos de investigadores👏
@dicma-csic.bsky.social
A TARGETED COMBINATION THERAPY ACHIEVES EFFECTIVE PANCREATIC CANCER REGRESSION AND PREVENTS TUMOR RESISTANCE https://www.biorxiv.org/content/10.1101/2025.08.04.668325v1
🔬 El proyecto del @iibm-csic-uam.bsky.social, con el #IRYCIS, investiga sobre el microbioma intestinal de pacientes con respuestas excepcionales a la inmunoterapia
👉 El objetivo final es descubrir fármacos para superar la resistencia en tumores refractarios a inmunoterapia
Congratulations Toni and team!! Super cool piece of work. IL1beta always in the spot!!
Durante la ‘Jornada Amigos y Amigas del CNIO’, el #CNIOStopCancer celebró la solidaridad, clave para atraer talento y avanzar en la investigación del cáncer. Quienes donan se encontraron con quienes investigan, para intercambiar emoción y conocimiento. 🧵
@juancarloslpz13.bsky.social estudia mutaciones en las células madre tumorales del tipo más frecuente y agresivo de cáncer de páncreas, el adenocarcinoma ductal, para lograr un diagnóstico más temprano y contribuir a desarrollar fármacos tanto prevenirlo como para tratarlo mejor.
Extremely happy and proud to share with you all our last article in @CR_AACR on the prometastatic role of PPAR-delta in pancreatic cancer. Check it out here:
aacrjournals.org/cancerres/ar...
Thank you Victor for the kind invitation and the opportunity to talk about my favourite topic!
Day 2 of our pancreatic cancer course was incredible! So excited about the amazing scientific content we covered today. From cancer stem cells to immune microenvironment - what a journey! 🔬✨ 🧪@ufvmadrid.bsky.social
Giving talks is one of the parts of this job that I love the most! Today twice. First, for the CNIO Friends initiative which support my postdoctoral work. Later, at Universidad Francisco de Vitoria about immune suppression in PDAC. What a joy to share science!!
Amazing first day of our pancreatic cancer summer course! Great attendance with young professionals eager to learn more about this disease - they are the future of better treatments 🔬
Fresh from the oven!! Our latest review published in @chp-pivot.bsky.social about the origin of PDAC CSCs and their inner and outer determinants by Diego Navarro and myself. A little bit of inflammation, a little bit of CIN, tons of stemness!! Enjoy!!
www.pivotscipub.com/chp/2/2/0010
Exciting opportunity: Emerging Clinical Academic Fellowship scheme, newly launched by CRIS Cancer Foundation and the ICR
We are offering a project within this scheme, please share!
👇 👇 🤩
www.icr.ac.uk/study-and-ca...
Saying goodbye to beautiful London after a terrific @transpan_cost meeting. So glad to present new data from the Exp Oncology lab and meet old and new friends fighting for new opportunities against PDAC.
Nice place to retire 🌲🌳
Two sides of scientific life lately. Yesterday, in the mountains in a bioinformatics retreat organised by CIBERONC, and today, at Fundación Ramón Areces for the CRIS Scientific Symposium.
Pancreatic cancer is projected to become the second-deadliest cancer by 2030, but new research from CSHL may offer a path forward. Professor David Tuveson & Research Investigator Claudia Tonelli have discovered a way to intercept pancreatic cancer before it fully forms.
📢‼️ Abierta la convocatoria de la VI Ayuda @fundacionfero.bsky.social-ASEICA para el Talento Joven en Cáncer
👨🔬🔬80.000€
🎯: Promover la investigación oncológica de personal joven investigador en España
🗓️Revisa los plazos de presentación
➡️ Cierre primera fase: 6/04👇
www.aseica.es/la-fundacion...
Yup
