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Färkkilä Laboratory

@farkkilab.bsky.social

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The Systems Medicine of Tumor Microenvironment Lab explores the dynamics of the tumor microenvironment through systems oncology to discover novel biomarkers Lead by @afarkkila.bsky.social 🌍📍 University of Helsinki, Finland 🔗 https://farkkilab.org/

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Färkkilä Laboratory @farkkilab.bsky.social · Nov 26

Hi there👋! We’re the Systems Medicine of Tumor Microenvironment Lab. Our passion? Exploring the #TME through #SystemsOncology. Harnessing the power of our diverse and multidisciplinary team, we use innovative approaches to uncover #Biomarkers and transform these insights into clinical applications.

Färkkilä Laboratory @farkkilab.bsky.social · Jul 8

Summer kick-off vibes from the #FärkkiläLab: we celebrated the start of the season (and our *brand new t-shirts👕*) with a BBQ party full of good food, laughs, and reflections. Looking back at a productive first half of the year and feeling motivated for what’s next. Let’s go🚀!

Färkkilä Laboratory @farkkilab.bsky.social · Jul 2

We’ve been a bit quiet from this account, but that’s about to change! Thrilled to share a huge milestone: our first PhD student, @fer-perezv.bsky.social, defended and graduated🎓! We’re sad to see him go, but so proud as he starts a postdoc at @harvardmed.bsky.social
Congrats, Fer💙!
#ProudLabMoment

Anniina Färkkilä @afarkkila.bsky.social · May 10

Was a great honour to host Iain McNeish on World Ovarian Cancer Day! And huge congratulations to my student Fernando Perez-Villatoro for successfully defending his PhD #wocd #proudsupervisor @farkkilab.bsky.social @helsinki.fi

Färkkilä Laboratory @farkkilab.bsky.social · Dec 12

@afarkkila.bsky.social, Sara, Ada, and Aleksandra are representing the lab at ESSB in Berlin!
Find them to discuss spatial biology!
🟠 Poster #88: Ada presents a spatial study of the cell cycle in #HGSC
🟠 Poster #155: Aleksandra showcases the use of ML to uncover spatial tumor ecosystems

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 11

📢Last chance! Final day to apply for our post-doc position!

🔬Join @afarkkila.bsky.social & the team in advancing #CancerResearch w/clinical impact in a collaborative and supportive environment.

📄Details here: farkkilab.org/careers/job-ads

⏳Apply today and/or help us spread the word by sharing!

Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

20/n Finally, thanks to @helsinkiuni.bsky.social, @fimm-uh.bsky.social, HUS, TYKS, and iCAN. We are proud to be part of these amazing and supportive communities.

Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

19/n Also, huge thanks to our funding agencies #ERC (projects SPACE and STRONGER), Sigrid Jusélius Foundation, Research Council of Finland, Cancer Foundation Finland, Foundation for the Finnish Cancer Institute, Instrufoundation. Let's continue fighting #HGSC together💪.

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

18/n Special thanks to Iga Niemic, @mariamhincapie.bsky.social, @erdoganpekcanerkan.bsky.social, @fer-perezv.bsky.social, and all the other co-authors and collaborators Peter Sorger, Sampsa Hautaniemi, Tuulia Vallius, Anni Virtanen, @ajitjohnson.com, @harvardlab.bsky.social & Johanna Hynninen.

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

17/n This long-term collab between our lab, @afarkkila.bsky.social and @anna-vaharautio.bsky.social lab was spearheaded by our amazing PhD student Inga-Maria Launonen and could have not been materialized without the help of all our amazing co-authors.

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

16/n In summary: our study sheds light on chemotherapy-induced myeloid-driven spatial T-cell exhaustion in #HGSC, opening new avenues for novel immunotherapeutic strategies to unleash CD8+ T-cell-mediated anti-tumor immunity.

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

15/n These results suggest that targeting the NECTIN2-TIGIT axis with ICB post-chemo, can reverse macrophage-driven CD8+ T cell exhaustion in #HGSC. Both TIGIT and NECTIN2 expression, even separately, predict functional response to anti-TIGIT therapy, making them strong biomarker candidates🎯.

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

14/n 📌TIGIT expression in CD8+ T cells correlates w/NECTIN2+ myeloid cell abundance.
📌TIGIT expression in CD8+ T cells and NECTIN2+ myeloid cell proportion correlated w/ex vivo CD8+ T cell activation after tiragolumab.
📌TIGIT expression predicts ex vivo response to pembro+tira in #iPDCs.

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

13/n Last but not least, we subjected matched tumors from our #iPDCs to #t-CyCIF single-cell analysis, focusing on NECTIN2 and TIGIT expression. These are our key findings:

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

12/n Next, we wondered🤔: What happens if we treat chemo-exposed patient cells with immunotherapy vs. chemo-naive cells? Using #iPDCs (immune-competent patient-derived cultures), we showed that immunotherapy after chemo enhances CD8+ T-cell activity, unlocking new therapeutic potential💥.

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

11/n (continuation)
📌Cancer cell-rich regions in the peritumoral TSI lack NECTIN2 and TIGIT/CD96, emphasizing macrophages' role in spatially regulating T cell exhaustion.

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

10/n Here’s what we found:
📌Chemo induces activated NECTIN2+ M1-like macrophages and exhausted, immune-checkpoint-positive CD8+ T cells, both co-localizing in the peritumoral stroma.
📌M1-like macrophages drive T cell exhaustion in #Myelonets, confirmed at the gene expression level.

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

9/n To integrate findings from both #t-CycIF and #scRNA-seq, we performed *t-CyCIF-guided spatial transcriptomics (GeoMx)* and deconvolution algorithms.

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

8/n From 22 paired patient samples (pre/post chemo)📊 we found that macrophage-dominated signaling is a key feature post-chemo, aligning with our spatial findings. Wondering what was the strongest induced interaction? NECTIN2 binding to CD226, & the inhibitory receptors CD96 & TIGIT on CD8+ T cells.

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

7/n To dig deeper, we turned to #scRNAseq 🧬! Chemotherapy induces not only spatial changes but also shifts in immune cell states. Post-treatment, we observe new states emerging for macrophages and T cells, while the diversity of cancer cells decreases. A dynamic TME ecosystem in action 🌌!

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

6/n However, these immune cells gain exhaustion markers, limiting anti-tumor immunity🛑. Notably, chemotherapy drives exhaustion in CD8+ T cells within M1-like myeloid neighborhoods.

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

5/n On the other hand, chemo reshapes the spatial landscape of #HGSC, transforming an spatially confined immunophenotype into a more infiltrated one. CD8+ T cells migrate from their “private” neighbourhoods toward cancer cell-hubs and #Myelonets.

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

4/n In summary, we showed that M2-like macrophage interactions limit CD8+ T cell interactions with tumor cells, resulting in inferior prognosis.

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

3/n Moreover, interactions between CD8+ T cells and M2-like macrophages at the TSI were mutually exclusive with sustained CD8+ T cell-tumor cell interactions and associated with shorter treatment responses.

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

2/n Spatial and molecular profiling of 117 #HGSC tumors pre- and post-chemo revealed a dynamic tumor ecosystem🔍. Using a high-plexed (30+🚨) antibody panel and #t-CycIF we identified #myelonets, interconnected networks of myeloid cells, as key drivers CD8+ T cell exhaustion upon chemotherapy.

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

1/n New paper alert 🚨 We're thrilled to share our just published paper in #CancerCell
Do you ever wonder how the #TME in #HGSC changes during chemotherapy? Check it here: www.sciencedirect.com/science/arti... and let’s dive into the highlights together #spatialbiology #ovariancancer #cancerresarch

Chemotherapy induces myeloid-driven spatially confined T cell exhaustion in ovarian cancer

Anti-tumor immunity is crucial for high-grade serous ovarian cancer (HGSC) prognosis, yet its adaptation upon standard chemotherapy remains poorly und…

www.sciencedirect.com

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Färkkilä Laboratory @farkkilab.bsky.social · Dec 10

A thread on our findings is coming later today—stay tuned! 📢

Anniina Färkkilä @afarkkila.bsky.social · Dec 10

Really happy to share our new publication! @anna-vaharautio.bsky.social Stay tuned for more insights! @farkkilab.bsky.social www.helsinki.fi/en/news/canc...

New insights into harnessing the immune system to combat ovarian cancer | University of Helsinki

Researchers have discovered how chemotherapy can change tumors, making them more vulnerable to new types of treatments. These findings could lead to personalized therapies that target the right patien...