Can a cancer exploit its environment and still resist treatment?.Yes, through co-existing malignant subclones!. Let me walk you through our latest study on how divergent evolution drives aggressiveness, and drug resistance of T cell cancer. 1/🧵.

Finally, we would also like to thank N. Borcherding (@theHumanBorch), M. Khodadoust, A. Herrera and A. Cheng for making their data public and their gracious assistance in the annotation and elaboration of their respective single-cell RNA sequencing data sets.

RT @TerkildB: Can a cancer exploit its environment and still resist treatment?.Yes, through co-existing malignant subclones!. Let me walk y….

And of course, this is the product of our fantastic community and facilities at @skinucph @UCPH_health @UCPH_Research!. #CancerResearch #Oncology #TCellLymphoma #CTCL #Hematology #TumorHeterogeneity #CancerBiology #DrugResistance #scRNAseq #CancerEvolution.

We greatly appreciate the constructive and professional feedback and suggestions from our reviewers and our editor @ElizSMcKenna at @CD_AACR!. We also thank @LEOFondet and the Danish Cancer Society @cancer_dk for funding the project!

This work was a team effort involving so many fantastic collaborators, clinicians, patients and their loved ones - and of course the incredible people in the group of Professor Niels Ødum. Too many people involved to list here - so go check out the paper!.

🎧 Prefer audio? We’ve generated two AI-narrated summaries of the study:. – A brief summary (~15 min) – A more in-depth version (~45 min) Great for listening on the go while diving into the details. 10/.

Our findings underscore that understanding this network of specialized cancer subclones is key to overcoming treatment resistance in L-CTCL. Mapping a patient's subclonal landscape guide personalized rational combination therapies targeting all subclones for enduring response. 9/

This discovery offers an explanation for varying treatment responses across different compartments in L-CTCL patients. By targeting infections and dampening inflammation, we expose these inherent vulnerabilities, making otherwise hard-to-treat subclones susceptible to therapy. 8/

Divergent evolution results in subclones that have different tissue preferences and respond differently to external factors: cytokines and infections. The most aggressive subclones are also most sensitive to treatment if stimuli are removed exposing their vulnerabilities. 7/

The trade-off⚖️: The subclones that respond most strongly to 🦠S. aureus toxins—the aggressive ones—are also the most intrinsically sensitive to 💊drugs when the stimuli are removed. This means reducing inflammation unmask therapeutic vulnerabilities in aggressive clones. 6/

S. aureus infections are a major clinical problem in CTCL, fueling malignant persistence. S. aureus toxins selectively activate certain subclones, while leaving others largely unaffected. This provides a selective advantage to responsive subclones!. But it comes at a price… 5/

These subclones show differences in tissue homing (skin/blood), metabolism, and immune signaling. Intriguingly, the subclone most abundant in blood often has less capacity for interacting with their inflammatory environment, correlating with reduced proliferation in the skin. 4/

Using single-cell scTCR+CITE-seq on matched skin and blood, we found 🧬genetically distinct malignant subclones in more than 80% of L-CTCL patients. Subclones have distinct RNA+protein signatures, are shared between blood and skin, and co-exist over extended periods of time⏳. 3/

TL;DR.👉Leukemic CTCL patients harbor functionally distinct co-existing subclones.👉Subclones respond differently to external factors such as infections and cancer drugs.👉The most aggressive subclones are also most sensitive to treatment if their extrinsic stimuli are removed 2/

RT @ElizSMcKenna: Now online in @CD_AACR: Divergent Evolution of Malignant Subclones Maintains a Balance Between Induced Aggressiveness and….

I have moved to the other place @terkild.bsky.social - I hope to see you there!.

RT @theJIDJournal: "Breaking the Vicious Cycle of Staphylococcal aureus Skin Colonization and Progression of Cutaneous T-Cell Lymphoma," a….

RT @skinucph: New @BloodJournal study by @ChellaKrishnaV and @TerkildB from Niels Ødum’s group @skinucph show bacterial infections can make….

RT @BloodJournal: Staphylococcus aureus and Sézary syndrome .#lymphoidneoplasia