Pereira Lab

Anchored screening identifies transcription factor blueprints underlying dendritic cell diversity and subset-specific anti-tumor immunity - Pereira Lab Highlights Anchored screening identifies ETS-IRF pairs and a third factor specifying DC subsets PU.1, IRF4, and PRDM1 induce a pro-inflammatory cDC2B-like identity SPIB, IRF8, and IKZF2 drive an i...

2/2 Exploring the sea of immune cell diversity, our work successfully maps future lanes for dendritic cell reprogramming and cancer immunotherapy!
Illustration by @azuravesta.bsky.social (azuravesta.com)
Read the full paper here: pereiralab.com/publication/...

1/2 Sharing exciting news! ✨
Our recently published paper “Anchored screening identifies transcription factor blueprints underlying dendritic cell diversity and subset-specific anti-tumor immunity” has been selected for the cover of the October issue of Immunity!
@cp-immunity.bsky.social

3/3 By collaborating with Karolinska Institutet, Peng will explore SM-assisted cDC1 reprogramming as a strategy to promote anti-tumor immunity. Way to go, Peng!

2/3 cDC1 reprogramming offers great immunotherapeutic promise. Yet, viral-mediated transcription factor delivery presents challenges of safety, cost, and scalability. Replacing TFs with SMs can potentially surpass these roadblocks.

Peng Wei Awarded a SciLifeLab PULSE Postdoctoral Fellowship - Pereira Lab The researcher Peng Wei from Pereira Lab was awarded a SciLifeLab PULSE Postdoctoral Fellowship for the project SMARD—Small Molecule-Assisted Cell Reprogramming to cDC1. The SciLifeLab PULSE is a comp...

1/3 Congrats to our team member @Peng Wei, who was awarded a SciLifeLab PULSE Postdoctoral Fellowship for his project SMARD, which will develop small molecule (SM)-assisted reprogramming to type 1 conventional dendritic cells (cDC1)!
For more info see: pereiralab.com/lab-news/pen...

2/2 Yet, dendritic cells had another go with Abigail Altman, who won the Best Poster Award with "Transcription factor blueprints underlying dendritic cell diversity", now out in Immunity (www.cell.com/immunity/ful.... Congrats to both! It's great to have our contributions recognized!

1/2 Celebrating a double win!✨ Yesterday, at the Lund Stem Cell Center (LSCC) retreat, Ervin Ascic was awarded the Article of the Year Award with our Science paper "In vivo dendritic cell reprogramming for cancer immunotherapy" (www.science.org/doi/10.1126/...)

3/3 If you feel you can contribute, reach out to mariana_faria.lopes@med.lu.se with a possible protocol title and small description.
Let’s connect to push forward a guide for cell engineering and reprogramming strategies! @springernature.com

2/3 The volume will cover: engineering immune cells with cellular reprogramming; viral and non-viral immune engineering; synthetic biology and genome editing to advance next-generation immune cells; clinical translation of cell engineering and reprogramming-based immunotherapies.

1/3 Call for Authors!
We are currently editing a volume on Cellular Reprogramming for Immunotherapy for the Methods in Molecular Biology series (Springer Nature). This volume will steer the future of the field and is a great way to share your lab’s protocols!

Huge thanks to Prof. Allison, and congrats to Ervin, who masterfully defended the promise of cell reprogramming for cancer immunotherapy!

We are proud to announce that Ervin Ascic successfully defended his PhD yesterday – with the special honor of Nobel Laureate James Allison as opponent! ✨
Ervin’s work makes a strong contribution, showing that in vivo dendritic cell reprogramming is paving the way toward the clinic.

17/17 🙏🏻 A big thank you to all the funding agencies for making this possible: @ERC_Research, @HorizonEU, @Cancerfonden, @Vetenskapsradet, @novonordiskfond, @fct_pt, #NextgenerationEU, @CancerResearch.

16/17 👥 We are grateful to our collaborators @AsgardThx, @medeea_matei, @FRosa93, @_CristianaPires, @IsabelUlmert, Signe Holst, Sun-Mi Park, Stefano Vergani, @Katha_lahl, @KharasLab, @TheYuanLab. We thank everyone for your contributions!

15/17 📖 We want to acknowledge the fantastic contribution from the Pereira Lab: Luis Oliveira, Abigail Altman, Ilia Kurochkin, Ervin Ascic, Evelyn Halitzki, Diogo Cabral, Malavika Nair @pedrocunha37.bsky.social, @WCMMLund, @Lunduniversity, @Lund_Stem , LUCC, @CNC_UC and Region Skåne.

14/17 🏠 Take-home: In this study we mapped the transcription factor toolkit that builds dendritic cell diversity — a blueprint for reprogramming immune cells against cancer. Read more: doi.org/10.1016/j.im...

13/17 🧩 Our results propose that ETS–IRF pairwise interactions constitute the foundation upon which any DC identity may be built and help define the drivers of DC divergence, advancing our understanding of DC specification and heterogeneity.

12/17 ⚖️ Surviving mice remained tumor-free upon rechallenge, showing durable immune memory. This finding points toward patient-tailored DC subsets as a new immunotherapy avenue.

11/17 🐭 Importantly, in melanoma (YUMM1.7) and breast cancer (EO771), in vivo reprogramming towards different iDC subsets drove orthogonal anti-tumor responses, mirroring the natural DC responsiveness on these tumors.

10/17 💉 In B16 melanoma tumor models, adoptive transfer of iDCs slowed growth and improved survival through distinct mechanisms: iDC2s boosted CD8+ and CD4+ T cells; iLDCs promoted myeloid infiltration.

9/17 ⚙️ Mechanistically, each TF triad had different chromatin engagement modes and co-bound subset-specific genes early on, showing that DC subset divergence is set in motion at the very start of reprogramming.

8/17 ⚔️ Functionally, iDC2s resembled inflammatory cDC2Bs with features of interferon-stimulated cDC2s, activating CD8+ T cells via antigen uptake, processing, and cross-presentation, demonstrating real immune potential.

7/17 🧪 iLDCs expressed an immature pDC gene signature but with a distinct, pro-inflammatory profile. Adding IRF4 to SII boosted IFN-β secretion nearly 5-fold, showing potential for interferon secretion.

6/17 🎯 iDCs showed subset-specific phenotypes (CLEC12A & SIRPα for PIP; LY6C & B220 for SII) without macrophage or lymphoid markers. PIP-induced cells (iDC2s) shared key cDC2 genes, and SII-induced cells (iLDCs) expressed many pDC genes but lacked some hallmarks (Siglech, Ly6D).

5/17 🔀 Both combinations rely on an ETS + IRF pair (PU.1/IRF4 or SPIB/IRF8) to prime DC identity. The third factor (PRDM1 or IKZF2) directs the subtype-specific program in induced dendritic cells (iDCs).

4/17 Screening in mouse embryonic fibroblasts revealed 2 key combos: PIP (PU.1, IRF4, PRDM1) activated Clec9a reporter & CD11b expression showing cDC2-like cell programming; SII (SPIB, IRF8, IKZF2) activated the Clec9a & hCD2 lymphoid reporters & BST2 expression- pDC-like cell

3/17 ⚓ We anchored the screen on known DC factors: PU.1, IRF8, and BATF3 induce cDC1s. When comparing their expression across subsets, PU.1 was enriched in cDC2s and IRF8 in pDCs, making them ideal starting points for discovering new “recipes”.

2/17 💡 Our approach: a direct cellular reprogramming sequential “anchored screen” of 70 TFs to identify regulators that specify type 2 conventional DCs (cDC2s) and plasmacytoid DCs (pDCs).

1/17 🔬 Dendritic cells (DCs) are a heterogeneous lineage of immune “sentinels” that orchestrates anti-tumor immunity. While several transcription factors (TFs) are known to control their development, how they cooperate to generate different DC subtypes has remained unclear. 🤔

📢 New in @ImmunityCP: We have mapped the transcription factor “routes” that program two dendritic cell subsets opening paths for personalized #cancer #immunotherapy. Read it here: doi.org/10.1016/j.im...
Here is a summary of what we discovered 🧵:
Illustration by @azuravesta.bsky.social