Dominant-negative PSMB10 disrupts immunoproteasome assembly and leads to transient T #lymphopenia. New study from Sujal Ghosh (University Hospital Düsseldorf), Yuqin Wang, Silke Meiners @fzborstel.bsky.social, Fabian Hauck @lmu.de and colleagues:
rupress.org/jhi/article/...

@esidsociety.bsky.social

Ghosh, Wang, Meiners, Hauck et al. describe a monoallelic dominant-negative PSMB10 variant that impairs immunoproteasome assembly & is associated with transient neonatal T #lymphopenia, highlighting a potentially dynamic & reversible form of early-life thymic dysfunction rupress.org/jhi/article/...

Stable genotype but transient phenotype ?
Dominant-negative PSMB10 disrupts immunoproteasome assembly and leads to transient T lymphopenia url: rupress.org/jhi/article/...

In @jhumimmunity.org, Ghosh et al. describe a monoallelic dominant-negative PSMB10 variant that impairs immunoproteasome assembly & is associated with transient neonatal T #lymphopenia, highlighting a potentially dynamic & reversible form of early-life thymic dysfunction rupress.org/jhi/article/...

Now at #ESMO25: In the phase 2 IKF/AIO PHERFLOT trial, perioperative FLOT + anti-PD-1 + anti-HER2 led to a pathological complete response rate of 48.4% in patients with resectable HER2+ esophagogastric adenocarcinoma @JosephTintelnot https://www.nature.com/articles/s41591-025-03979-y

CAR T cell engineering impacts antigen-independent activation and co-inhibition Schultheiß, Stücheli and colleagues compare viral and non-viral engineering of CAR T cells targeting a leukemia neoepitope. They reveal that manufacturing mode and CAR design significantly shape T cel...

www.cell.com/molecular-th...

Out now @moltherapy.bsky.social Methods & Clin Dev‬: We show that CAR T-cell biology is shaped not just by CAR design but also by engineering method. Sleeping Beauty vs lentiviral platforms imprinted distinct activation & exhaustion-like states - important for future CAR T optimization. Read at👇

Inflammation and limited adaptive immunity predict worse outcomes on immunotherapy in head and neck cancer - npj Precision Oncology npj Precision Oncology - Inflammation and limited adaptive immunity predict worse outcomes on immunotherapy in head and neck cancer

Congrats to Mascha Binder & her team @binderlab.bsky.social‬ on their new paper showing that blood-based inflammation markers-like IL-6 & cfDNA-are better than PD-L1 at predicting immunotherapy outcomes in head & neck cancer.A move toward smarter, tailored treatments. www.nature.com/articles/s41...

Tmem127-mediated immune receptor degradation regulates T cell homeostasis through the common gamma chain www.biorxiv.org/content/10.1101/2025.07....

Tmem127-mediated immune receptor degradation regulates T cell homeostasis through the common gamma chain www.biorxiv.org/content/10.1101/2025.07....

The immunoproteasome disturbs neuronal metabolism and drives neurodegeneration in multiple sclerosis Neuronal proteasomal dysfunction is a hallmark of neuroinflammatory and neurodegenerative diseases. This study reveals that the interferon-induced immunoproteasome drastically decreases proteasomal ac...

Our latest work:
The immunoproteasome disturbs neuronal metabolism and drives neurodegeneration in multiple sclerosis: Cell www.cell.com/cell/fulltex...

Excited to co-found and help lead @imprintlabs.bsky.social —a focused effort to decode the immune system’s memory through cutting-edge computation and experimentation. Grateful to be on this journey with an exceptional team.

UV1 vaccination in pembrolizumab-treated patients with recurrent or metastatic head and neck cancer: A randomized multicenter phase 2 trial The phase 2 FOCUS trial evaluated the hTERT vaccine UV1 plus pembrolizumab in recurrent/metastatic PD-L1+ head and neck cancer patients. UV1 was safe, did induce T cell responses, but it did not improve efficacy over pembrolizumab alone, suggesting limited benefit in this setting.

Online Now: UV1 vaccination in pembrolizumab-treated patients with recurrent or metastatic head and neck cancer: A randomized multicenter phase 2 trial

Huge congrats to Christoph Schultheiß & Paul Schmidt-Barbo for this great work, and thanks to Ivona Aksentijevich & Daniel L. Kastner from NIH for their support! Read at JACI:
www.jacionline.org/article/S009...

We also developed a machine learning model that accurately distinguishes DADA2 patients from healthy individuals based solely on immune repertoire metrics, rather than sequence-level labels—shedding light on the unique immunogenetic signature of DADA2!

Excited to share our latest study on DADA2. We analyzed 52 patients, observing HGG, loss of T & B cell memory and persistent proinflammatory cytokines despite anti-TNF therapy. Notably, the B cell architecture was skewed toward IGHV4-34, a feature often seen in malignant B cells.

New Links Between Immune Dysfunction & Lymphoma Uncovered (Image: Adobe Stock, KI)

Binder Lab: Immune Changes & Lymphoma Risk
🔬 DADA2 mutations disrupt immune balance—low antibodies, memory B/T loss & inflammation. binderlab.bsky.social links IGHV4-34 B cells to autoimmunity & lymphoma. Their ML tool detects DADA2 via immune architecture! 📖 More: www.jacionline.org/article/S009...

IGLV3-21-R110-directed bispecific antibodies activate T cells and promote killing in a high-risk subset of chronic lymphocytic leukemia www.biorxiv.org/content/10.1101/2025.02....

Congratulations to Claudia Fischer for this achievement and also many thanks to Matthias Peipp from UKSH, Heinz Läubli and Obinna Chijikoe @biomedizin.unibas.ch as well as Marie Follo @uniklinik-fr.bsky.social and Nicholas Chiorazzi from Feinstein Institutes, NY.

IGLV3-21-R110-directed bispecific antibodies activate T cells and promote killing in a high-risk subset of chronic lymphocytic leukemia We previously used a disease-specific B cell receptor (BCR) point mutation (IGLV3-21-R110) for selective targeting of a poor-risk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen rec...

Very happy to see this finally out @bioRxiv: We generated a bispecific antibody targeting the IGLV3-21-R110 CLL-specific driver mutation. Read here:
www.biorxiv.org/content/10.1...

We observed phenotypic differences in T cells based on production methods - even without antigen exposure. In addition, transposon-based production appears to promote an exhaustion-like phenotype via RIG-I sensing of transposase-encoding mRNA.

Happy to share our new preprint reporting a direct comparison of transposon-based and lentiviral CAR T cell manufacturing approaches. Read at @biorxivpreprint.bsky.social . doi.org/10.1101/2025...