Neuroinflammation in Alzheimer disease - Nature Reviews Immunology This Review provides an in-depth examination of how inflammation contributes to neurodegeneration in Alzheimer disease. The authors explore the impact of extrinsic factors, such as brain trauma, diet ...

it's big, and it's a review of 601 papers on the topic - but here's an update on Neuroinflammation in Alzheimer's Disease
www.nature.com/articles/s41...

led by Michael Heneka, published in @natrevimmunol.bsky.social today

(MANY more authors listed and linked below)

The brain's immune protection from its borders, including the bone marrow of the skull and 3 meninges layers

Guardians of the Brain.
A brief review of 6 recent, important reports that help us understand the brain-immune system axis
erictopol.substack.com/p/guardians-...
in the new Ground Truths, open-access (free)
relevance: #LongCovid, brain tumors, multiple sclerosis, ME/CFS, autoimmunity

Programming tissue-sensing T cells that deliver therapies to the brain To engineer cells that can specifically target the central nervous system (CNS), we identified extracellular CNS-specific antigens, including components of the CNS extracellular matrix and surface mol...

Wowza! Lim lab drops bombs in 2s! www.science.org/doi/10.1126/...

www.science.org/doi/10.1126/...

1) GREAT DEBATE: Pre-treatment #predictive #biomarkers: INF-y vs. #Immunoscore vs. #multiplexIF /next-generation #spatialbiology. A 3-way debate..
Drs. Christian Blank vs Jerome Galon vs Janis M. Taube. Dr Blank starts. IFNg sig improves 2 ID pts who need more Tx #Bridge2024 @sitcancer.bsky.social

Figure 10. How CXCL12/CXCR4 mediates VEGFC/VEGFR3/PI3K activities to regulate lymphatic development. CXCL12 is primarily expressed by Schwann cells in the peripheral nerves in the dermal skins of E14.5 embryos. CXCL12/CXCR4 is required for maintaining cell surface levels of VEGFR3 in LECs. VEGFC stimulation triggers CXCR4/VEGFR3 internalization and subsequently VEGFR3/PI3K/AKT signaling to regulate lymphatic development. Our results also indicate that VEGFC treatment upregulates CXCR4 expression, which might serve as a positive-feedback loop to enhance VEGFC/VEGFR3 signaling (dashed lines). Created in BioRender. Do, L. (2024) https://BioRender.com/j33w742.

A neuro-lymphatic communication guides lymphatic development by CXCL12 and CXCR4 signaling

Read this Research Article by Long Nguyen Hoang Do, Xiaolei Liu @templemedschool.bsky.social and colleagues:
https://buff.ly/49lSHLb

NKG2A-mediated immune modulation of NK cells by Staphylococcus aureus
www.biorxiv.org/content/10.1...

Could one envision a synthetic receptor technology that is fully programmable, able to detect diverse extracellular antigens – both soluble and cell-attached – and convert that recognition into a wide range of intracellular responses, from gene expression and real-time fluorescence to modulation..

Induced B-Cell Receptor Diversity Predicts PD-1 Blockade Immunotherapy Response. www.biorxiv.org/content/10.1101/2024.12....

T cell receptor–centric perspective to multimodal single-cell data analysis T cell receptor–centric perspective improves single-cell analysis.

T cell receptor–centric perspective improves single-cell analysis
www.science.org/doi/10.1126/...

T cell receptor–centric perspective to multimodal single-cell data analysis T cell receptor–centric perspective improves single-cell analysis.

Our massive effort to recontextualize #single #T-cell data is now out in Science Advances! We developed a new system, STEGO, to do a TCR-first analysis, and reanalyzed 12 studies and more than 500 000 individual T-cells.
Supported by @cziscience.bsky.social !
doi.org/10.1126/scia...

Spatial organization of astrocyte clones: The role of developmental progenitor timing Astroglial clones vary in distribution, within or across cortical layers. Distribution of clones depends on their origin. Layer-specific clones have fewer, less dispersed cells. Juxtavascular clones...

onlinelibrary.wiley.com/doi/10.1002/...

Cancer cells impair monocyte-mediated T cell stimulation to evade immunity - Nature Inflammatory monocytes are identified as important players in T cell restimulation in the tumour microenvironment.

Cancer cells impair monocyte-mediated T cell stimulation to evade immunity:

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

Integrative mapping of human CD8+ T cells in inflammation and cancer - Nature Methods scAtlasVAE is a deep learning-based model for cross-atlas integration. Here it enables the development of a large-scale human CD8+ T cell atlas with integrated T cell receptor data.

Integrative mapping of human CD8+ T cells in inflammation and cancer
www.nature.com/articles/s41...
www.nature.com/articles/s41...

The redox sensor KEAP1 facilitates adaptation of T cells to chronic antigen stimulation by preventing hyperactivation KEAP1 promotes persistent T cell immunity and a stem-like T cell response during chronic antigen stimulation by repressing NRF2.

KEAP1-mediated suppression of NRF2 required for optimal expansion of CD8+ T cells during chronic antigen exposure:

www.science.org/doi/10.1126/...

A splicing isoform of PD-1 promotes tumor progression as a potential immune checkpoint - Nature Communications Whether PD-1 splicing isoforms impact T cell anti-tumor capacity has not been fully illustrated. Here the authors identify a human PD-1 isoform, PD-1^28, which functions to suppress anti-cancer immuni...

"Here, we identify an alternative splicing isoform of human PD-1, which carries a 28-base pairs extension retained from 5′ region of intron 2 (PD-1^28), is expressed in peripheral T cells and tumor infiltrating lymphocytes."
#Immunology #Immunotherapy
www.nature.com/articles/s41...

✨ Ever wondered why B cells are so fond of IL-2? Wonder no more! Our study is now published in Immunity @cellpress.bsky.social 🔍📑 A truly perfect Thanksgiving gift! 🧑‍🔬💉🔬https://authors.elsevier.com/c/1kAq43qNrUxuTR

Interleukin-15-armoured GPC3 CAR T cells for patients with solid cancers - Nature We evaluate the effects in humans of interleukin-15 co-expression on glypican-3 (GPC3) chimeric antigen receptor (CAR) T cells and demonstrate that IL-15 increases the expansion, intratumoural su...

new out in Nature www.nature.com/articles/s41...

This paper is now online: www.nature.com/articles/s41... and it is fascinating!!

Nivolumab plus Ipilimumab in Microsatellite-Instability–High Metastatic Colorectal Cancer | NEJM Patients with microsatellite-instability–high (MSI-H) or mismatch-repair–deficient (dMMR) metastatic colorectal cancer have poor outcomes with standard chemotherapy with or without targeted therapi...

Nivolumab plus Ipilimumab in Microsatellite-Instability–High Metastatic Colorectal Cancer
www.nejm.org/doi/full/10....

A platform for multimodal in vivo pooled genetic screens reveals regulators of liver function Organ function requires coordinated activities of thousands of genes in distinct, spatially organized cell types. Understanding the basis of emergent tissue function requires approaches to dissect the...

Sometimes I read a pre-print that moves the needle, typically on bioRxiv where all the good new stuff first appears. Two first class tech-dev pioneers and their fearless postdocs collaborate creating tour de-force methods -->
www.biorxiv.org/content/10.1...

Integrative pathway analysis across humans and 3D cellular models identifies the p38 MAPK-MK2 axis as a therapeutic target for Alzheimer’s disease
www.cell.com/neuron/fullt...

Neural Guidance of Lymphatics

#SchwannCell CXCL12⏫ Sprouting/Patterning of CXCR4+ #LymphaticEndothelialCell

Prox1-CreERT2:Cxcr4f/f🐭
⬇️ Lymphatic Valve formation
⬇️ VEGF-C-induced #Lymphangiogenesis

Xiaolei Liu lab Development 2024 @biologists.bsky.social
journals.biologists.com/dev/article-...

Macrophages and nociceptor neurons form a sentinel unit around fenestrated capillaries to defend the synovium from circulating immune challenge - Nature Immunology Why joints are highly responsive to systemic inflammation is unknown. Hasegawa et al. sought to address this question, developing a whole-mount imaging system of the entire synovium to profile the vas...

Macrophages and nociceptor neurons form a sentinel unit around fenestrated capillaries to defend the synovium from circulating immune challenge
www.nature.com/articles/s41...

Next-generation combination approaches for immune checkpoint therapy - Nature Immunology In this Review, Sharma and colleagues describe the current landscape of combination therapies and discuss requirements for the development of effective combination strategies.

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

Sharing our latest review article to highlight the importance of appropriately developing combination strategies for immune checkpoint therapy. Grateful for working with 3 brilliant scientists: Sangeeta Goswami, Kristen Pauken & Linghua Wang

The hallmarks of cancer immune evasion Cancer cells often evade the host immune system, challenging the effectiveness of immunotherapy. In this comprehensive review, Galassi et al. summarize key mechanisms of immune evasion within the “thr...

The hallmarks of cancer immune evasion

Structure of an Autoimmune T Cell Receptor Complexed with Class II Peptide-MHC: Insights into MHC Bias and Antigen Specificity T cell receptor crossreactivity with different peptide ligands and biased recognition of MHC are coupled features of antigen recognition that are nece…

continuing on #TCR #Crossreactivity "recognition of structurally distinct agonist peptides is not indicative of #TCR #promiscuity, but rather #highly #specific alternative solutions to TCR engagement" www.sciencedirect.com/science/arti...

Dendritic cells maintain the CAR T cell pool in irradiated tumors
www.biorxiv.org/content/10.1...

Spatial interactions of immune cells as potential predictors to efficacy of toripalimab plus chemotherapy in locally advanced or metastatic pancreatic ductal adenocarcinoma: a phase Ib/II trial - Sign... Signal Transduction and Targeted Therapy - Spatial interactions of immune cells as potential predictors to efficacy of toripalimab plus chemotherapy in locally advanced or metastatic pancreatic...

Spatial interactions of immune cells as potential predictors to efficacy of toripalimab plus chemotherapy in locally advanced or metastatic pancreatic ductal adenocarcinoma: a phase Ib/II trial #PancreaticCancer 🧪 www.nature.com/articles/s41...

Solid tumor immunotherapy using NKG2D-based adaptor CAR T cells NKG2D ligands are widely expressed by solid tumors providing an attractive targeting opportunity with NKG2D-based CAR T cells. Here, Obajdin et al. show that this is optimally achieved using an adapto...

"We report that profound and durable efficacy together with functional CAR T cell persistence is achieved in a range of challenging solid tumor models using NKG2D-containing adaptor CARs in which signaling is provided by Dap10 & a single ITAM source, notably Dap12"
#Immunology #Immunotherapy

From @brodskyigorlab.bsky.social et al
"Altogether, our data reveal that TLR priming tunes the threshold for the murine NAIP/NLRC4 inflammasome to enable inflammasome responses against immunoevasive or suboptimal NAIP ligands."
#Immunology #InnateImmunity
www.pnas.org/doi/abs/10.1...