Daniel Hoces

Our new review article led by Jordan Kramer:

Platforms for studying cell–cell recognition by immune cells

onlinelibrary.wiley.com/doi/10.1111/...

As promised, a 'skeet' -orial on our paper published last week !

Continuous expression of TOX safeguards exhausted CD8 T cell epigenetic fate TOX safeguards exhaustion biology in established Tex cells and restrains fate conversion to Teff cells.

Excited to share my graduate work from the @ejohnwherry.bsky.social lab on the molecular mechanisms locking in the differentiation fate of exhausted CD8 T cells (Tex), published earlier this month in @science.org immunology. Main findings below!
www.science.org/doi/10.1126/...

ICYMI by First release - now in print @science.org

Identification of APCs in the gut that promote Treg differentiation and how tolerance to food antigens is influenced by helminth infection.

buff.ly/3DjNQ1e

By @cicacanesso.bsky.social @danmucida.bsky.social @victora.bsky.social et al

Our paper is finally out in @immunolcellbiol.bsky.social, think that transcription factor expression is all that? Well not if the genome is not prepared in a way to allow binding: here is a short 🧵1/

1/ Ever wonder how a clearly brilliant person – someone great a math and engineering and company building – can display shockingly unintelligent thinking when it comes to politics? Neuroscience has the answer!

Two weeks left to apply for a postdoc position with the Slack group! Please spread the word!

Could you please add me to the pack? Thank you very much!

Our new work!

The 3D affinities of the OT-I TCR to foreign and self-antigens predict their 2D affinities and reveal imperfect antigen discrimination

www.biorxiv.org/content/10.1...

Two studies published in @nature.com today showing that Tpex-like cells develop independent from acute or chronic infection

#Tpex

www.nature.com/articles/s41...

Our work led by Anna Huhn is now published!
The molecular reach of antibodies crucially underpins their viral neutralisation capacity
lnkd.in/epe8YZPm

Thank you to the reviewers for constructive feedback!

A timed epigenetic switch balances T and ILC lineage proportions in the thymus Highlighted Article: Delayed activation of the T-cell lineage commitment regulator Bcl11b in mouse thymic progenitors due to distal enhancer deletion reduces T-cell output and increases Zbtb16-driven ...

Happy New Year! Excited about our new study on a timed epigenetic switch controlling T cell and ILC lineage decisions in the thymus! In a nutshell: timing is everything.

The study was led by the fantastic @nickpease.bsky.social. A thread: (1/n)

doi.org/10.1242/dev....

Thrilled to share our @sciimmunology.bsky.social paper! We report that rodent PD-1 is weaker than human PD-1 (reduced ligand binding & signaling) & lacks a conserved vertebrate motif. Humanizing mouse PD-1 disrupts T cell anti-tumor responses, raising many questions. science.org/doi/10.1126/...

Prior antigen experience of CAR T cells determines functional attributes and amenability to transcription factor-mediated functional enhancement
www.nature.com/articles/s41...
@koledegolier.bsky.social
www.nature.com/articles/s41...

Biologist, stop putting UMAP plots in papers!

Blogpost here: simplystatistics.org/posts/2024-1...

'The TME of Long Term Survival cases was distinguished by coinfiltration of T cells, B cells & plasma cells, along with upregulation of the PD-1/PD-L1 pathway. Remarkably, these prognostic associations were almost entirely restricted to tumors with high-epithelial content & the C4/DIF mol. subtype'

"(...) reinforcing 41BB costimulation on the day of vaccination did not result in a substantial improvement in vaccine responses. However, reinforcing 41BB costimulation on day 4 after vaccination, when 41BB expression levels were highest, resulted in a profound improvement in CD8+ T cell responses"

🖐️ Hi Mam! - A superantigen (MAM) goes to the head of the class (II) to find alternatives to TCRs for specific peptide:MHC binders doi.org/10.1038/s415...

This is a clever way to use synthetic biology: taking a toxin that overactivate the immune system (superantigen), rationally modify its core components and transform it into a platform of immunotherapy agents.
Congratulations to @haotiandu.bsky.social and @possuhuanglab.bsky.social on the 2 papers!

1/ In two back-to-back papers, we present our de novo TRACeR platform for targeting MHC-I and MHC-II antigens

TRACeR for MHC-I: go.nature.com/4gcLzn5
TRACeR for MHC-II: go.nature.com/4gj5OQk

Out this week @science.org by first release: Specific combinations of nutrients and metabolic enzymes determine T cell differentiation via loci-specific histone acetylations.

https://buff.ly/4gvqKTz

From Shixin Ma, Sue Kaech @tcellogic.bsky.social and colleagues

#Immunology #immunometabolism

Check out our last pub. from @mfgrp.bsky.social al lab! We discovered that skin commensal microbes induce systemic and local B cell responses upon colonization and took advantage of this knowledge to create topical vaccines using engineered skin microbes. Please read the thread for details.

Today we report that an engineered skin bacterium, swabbed gently on the head of a mouse, can unleash a potent antibody response against a pathogen. Could lead to topical vaccines that are applied in a cream. @djenetbousbaine.bsky.social led the charge... @natureportfolio.bsky.social 1/55

EsoBiotec Begins Clinical Trial of In Vivo BCMA CAR-T Candidate ESO-T01 for Multiple Myeloma ESO-T01 is the first in vivo BCMA CAR-T candidate to reach the clinical stage Early clinical data are expected in second half of 2025 MONT-SAINT-GUIBERT, Belgium, Dec. 11, 2024 (GLOBE NEWSWIRE) -- Eso...

In #biotech #celltherapy news, in vivo CAR T company #Esobiotec has dosed Patient 1 with their proprietary lentiviral therapy for rrMM finance.yahoo.com/news/esobiot...
joining the top tier with Interius, Umoja etc. Disclosure: I'm an independent Board Member and wicked proud of the team.

Interestingly, the presence of circulating B cells is what determines the formation of clusters (and trapping) of many CAR Ts in the lung. That may also may explain homing in the spleen. Not so sure about the live though.

Single-cell imaging of CAR T cell activity in vivo reveals extensive functional and anatomical heterogeneity Cazaux et al. use intravital imaging to dissect anti-CD19 CAR T cell activity. This study uncovers both anatomical and functional diversity in the outcome of anti-CD19 CAR T cell interactions with tum...

I believe their homing is a combination of the dosing route (iv)+ target availability in the tissue. This is a great paper on anti-CD19 CAR Ts homing in mice. pmc.ncbi.nlm.nih.gov/articles/PMC...

This was very surprising for me when I look it in mice, but it seems to be similar in human: many get trapped in the lung and the mostly home in liver and spleen. Makes you wonder if that initial homing is the key difference between success and failure of CAR Ts in blood cancer vs solid tumors

Fascinating study where they label CAR T cells and follow their trafficking in patients! Immediate biodistribution is to the liver and spleen, and they can see whether the Car goes into extramedullary masses. What explains differences between patients?

NiCo is out! Our new algorithm for spatial transcriptomics data analysis predicts the crosstalk of cell types co-localized in tissue niches and sheds light on signalling mediators and downstream effects of cell-cell interactions by inferring covarying gene programs.

www.nature.com/articles/s41...

Engineering cells as “live-drugs” is a promising therapeutic strategy, with applications that go beyond cancer. Congrats to Nishith and Milos! Great to see your work published!