Ruffell Lab

People with some cancers live longer after a COVID vaccine mRNA vaccines seem to boost the effectiveness of an immune therapy for skin and lung cancer ― in an unexpected way.

People with some cancers live longer after COVID vaccination 😮

mRNA vaccines can augment immune checkpoint inhibition efficacy for patients with skin or lung cancers - by globally boosting immune responses 💉🧪⚕️

www.nature.com/articles/d41...

Grippen et al study:
www.nature.com/articles/s41...

Activation and regulation of cGAS-STING signaling in cancer cells Cancer-intrinsic genomic instability drives cytosolic DNA accumulation, triggering cGAS-STING immune signaling. Shim et al. review recent advances in cancer/cGAS-STING crosstalk, with a molecular-level focus on sources of cytosolic DNA and immunoregulatory mechanisms, including their therapeutic implications.

Activation and regulation of cGAS-STING signaling in cancer cells

Antigen-presenting cells as arbiters of mucosal tolerance and immunity Nature Immunology - Brown and colleagues review the heterogeneity of mucosal antigen-presenting cells that orchestrate T cell immunity to intestinal antigens.

Excited to share our review on Thetis cells and dendritic cells, and their roles in mucosal immunity and tolerance @natimmunol.nature.com rdcu.be/eLtB1

Now online in Cancer Discovery @aacrjournals.bsky.social: Recurrent Immunogenic Neoantigens and Their Cognate T-cell Receptors in Treatment-Resistant Metastatic Prostate Cancer - by Nofar Gumpert, Shira Sagie, @yardenasamuels.bsky.social, and colleagues doi.org/10.1158/2159...

Developing SEMA4A-directed CAR T cells to overcome low BCMA antigen density in multiple myeloma Di Meo et al. demonstrate that multiple myeloma relapses after CAR T cell therapy frequently express low BCMA levels by quantifying target antigen density on patient samples. SEMA4A regulates MM cell proliferation, migration, tissue infiltration, and osteoclast formation. SEMA4A-directed CAR T cells show superior activity in eradicating BCMAlow MM than BCMA-CAR T cells.

Online Now: Developing SEMA4A-directed CAR T cells to overcome low BCMA antigen density in multiple myeloma

Read more about work just published online in Cancer Discovery @aacrjournals.bsky.social by Iris Mimpen, Thomas Battaglia, Miguel Parra Martinez, Emile Voest, and colleagues at @nkinl.bsky.social below and here: doi.org/10.1158/2159...

Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumours - Nature An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and develop...

🔬Our paper from the @miriammerad.bsky.social lab is now online! This is a story shaped over years of cross-disciplinary endeavor at @sinaiimmuno.bsky.social and labs across the world. 🧵:
www.nature.com/articles/s41...

A TLR4-dependent fibroblast-monocyte axis in tumor-draining lymph nodes contributes to metastasis in triple-negative breast cancer Triple-negative breast cancer (TNBC) is characterized by high risks of relapse or metastatic disease. Mattavelli et al. identify a chemokine axis that recruits immunosuppressive monocytes to tumor-draining lymph nodes. By co-targeting this recruitment, the TNBC response to immune checkpoint blockade is augmented and metastasis to the lung is reduced.

Online now: A TLR4-dependent fibroblast-monocyte axis in tumor-draining lymph nodes contributes to metastasis in triple-negative breast cancer

Integrin CD103 expression in naive CD8+ T cells promotes cytokine-driven acquisition of memory phenotype and effector function Integrin CD103 mediates memory T cell tissue residency by binding E-cadherin-expressing epithelial cells, but why CD103 is also expressed on circulating naive CD8+ T cells has been unclear. Li et al. report that CD103 facilitates the interaction of naive CD8+ T cells with E-cadherin-expressing dendritic cells that in turn provide cytokine-mediated cues to promote their differentiation into memory-phenotype effector T cells.

Online now: Integrin CD103 expression in naive CD8+ T cells promotes cytokine-driven acquisition of memory phenotype and effector function

How can we reawaken the body’s own anti-viral defenses to fight brain cancer?

Delighted to share our new study where we now answer this question, led by the brilliant @alvarezprado.bsky.social who is now an independent PI at LIH Luxembourg 👏👏

#BrainTIME 🧠🦠🧪
🧵

www.sciencedirect.com/science/arti...

Lymphoma accelerates T cell and tissue aging Hesterberg et al. show that lymphoma provokes marked and rapid changes in young T cells that recapitulate the transcriptional, epigenetic, and senescent features manifest in aged T cells, including aging-associated alterations in inflammation, proteostasis, and iron homeostasis that also occur in other tissues of lymphoma-bearing individuals.

Online Now: Lymphoma accelerates T cell and tissue aging

Lipid nanoparticles as a tool to dissect dendritic cell maturation pathways Rennen et al. provide methods to distinguish homeostatic from immunogenic mature cDC1s, based on lipid nanoparticle (LNP)-induced maturation. Only the uptake of TLR ligand- or mRNA-encapsulated LNPs i...

In the new Resource paper from Sofie Rennen and @victor-bosteels.bsky.social, published in @cp-cellreports.bsky.social, they present a method to reliably annotate them. www.cell.com/cell-reports...

#InterferonPower! Thrilled for our latest work @cp-cell.bsky.social! With @danielboehmer.bsky.social, we dug into tons of papers & created what we hope will be a go-to resource for immunologists & non-immunologist about type I, II, III (& IV😉) #interferons! Free👉 authors.elsevier.com/a/1leKGL7PXu...

I am beyond excited and incredibly proud to share that our work is now out in @nature.com This discovery was made possible thanks to the first author Kostas kelepouras, my fantastic lab , and the unique research environment here in Cologne in collaboration with the Hospital bambino Gesu in Rome.

Dendritic cells function beyond antigen presentation In this issue of Cancer Cell, Chen et al. identify DNASE1L3-expressing dendritic cells (DCs) as enhancers of anti-tumor immunity. By degrading neutrophil extracellular traps, these DCs promote CD8⁺ T cell infiltration into tumors and enhance checkpoint blockade efficacy, extending DNASE1L3’s known immune regulatory role to physical remodeling of the tumor microenvironment.

Online Now: Dendritic cells function beyond antigen presentation

DNASE1L3-expressing dendritic cells promote CD8+ T cell function and anti-PD-(L)1 therapy efficacy by degrading neutrophil extracellular traps CD8+ T cell exclusion and dysfunction in the tumor microenvironment (TME) are among the most challenging obstacles for anti-PD-(L)1 therapy. Here, we …

Dendritic cells! What can’t they do?!

In addition to being the surveilling determinants of self vs. non-self, they can degrade NETs, unmasking tumors protected by suppressive neutrophils.

www.sciencedirect.com/science/arti...

TNF and type I interferon crosstalk controls the fate and function of plasmacytoid dendritic cells - Nature Immunology Plasmacytoid dendritic cells are type 1 interferon (IFN-I)-producing antiviral specialists that have been shown to be able to differentiate into conventional dendritic cells. Here the authors show how...

🚨 Our latest paper is out in @natimmunol.nature.com ! 🧵
Plasmacytoid dendritic cells (pDCs) — the immune system’s IFN-I powerhouses — can change their identity!
Congrats to @rebecaarroyo.bsky.social, our team & collaborators 👏👏
🔗 www.nature.com/articles/s41...

Fc-optimized CD40 agonistic antibody elicits tertiary lymphoid structure formation and systemic antitumor immunity in metastatic cancer Osorio et al. report a first-in-human study of intratumoral 2141-V11, an Fc-engineered CD40 agonistic antibody, showing it is safe and induces systemic and durable antitumor immunity in patients with ...

Thrilled to share our new publication on the first-in-human phase 1 trial of intratumoral Fc-engineered CD40 agonistic antibody 2141-V11 in metastatic cancer. Over 10 years of preclinical work at the Ravetch lab led to this moment, made possible by an amazing team! 🧵 🪡 www.cell.com/cancer-cell/...

TIM3+ breast cancer cells license immune evasion during micrometastasis outbreak Rozalén et al. report that TIM3 in breast cancer drives a specific mechanism of immune escape during micrometastasis. TIM3+ tumor cells exhibit stemness/EMT features and promote immune-evasion by inducing immunosuppressive γδ T cells. TIM3 is a biomarker of poor outcome, and its blockade targets metastasis initiating cells during micrometastasis.

TIM3+ breast cancer cells license immune evasion during micrometastasis outbreak

It’s out!!!!! We hope our review on aging, immunity, and cancer is helpful.

Such a rewarding group effort led by Melissa Dolan, with Kendra Libby, Alison Ringle, and @vangalenlab.bsky.social

So grateful to @gabriellebrewer.bsky.social @natrevcancer.nature.com for her efforts and support

YouTube video by Francis Crick Institute The Past, Present and Future of Immunology Research – with Caetano Reis e Sousa

My "Crash Course in …Immunology" is now posted on YouTube youtu.be/nBC9vvlTxF8. Taken from a public lecture @crick.ac.uk on history and basic concepts in immunity. Aimed at the lay public and those seeking an introductory overview.

Delighted that our paper describing cDC1 states and their distribution in mouse tumours is out today in @eurjimmunol.bsky.social. Many congratulations to Cécile Piot who led this work and brought it to conclusion! onlinelibrary.wiley.com/doi/10.1002/...

Tumor-associated neutrophil precursors impair homologous DNA repair and promote sensitivity to PARP inhibition - Nature Communications Tumor-associated neutrophils exhibit heterogeneity in breast cancer. Here, the authors identify a distinct precursor population (PreNeu) in estrogen receptor-positive tumors. PreNeu suppress homologou...

🚀 Excited to share our latest publication!
👉 www.nature.com/articles/s41...
A fantastic collaboration with an incredible team.

#BreastCancer #Neutrophils #TumorMicroenvironment #PARPinhibitors #DNARepair #NatureCommunications #CancerImmunology #CalcinottoLab

Myeloid cell networks govern re-establishment of original immune landscapes in recurrent ovarian cancer Ghisoni et al. profile the immune landscape of 697 ovarian cancers (OCs), identifying four immune phenotypes linked to prognosis and treatment response. The study demonstrates that BRCA-dependent TIL:...

This new study from Dangaj& Ghisoni in Cancer Cell analyzed 131 matching primary/relapsed ovarian cancers, to show that the immune landscape of the original tumor is re-established in the recurrent lesion, which depends on HRD status and pre-existing TIL:myeloid niches. www.cell.com/cancer-cell/...

Adoptively transferred Th17 cells cooperate with host B cells to achieve durable tumor immunity Cole et al. report that adoptively transferred, tumor-specific Th17 cells engage host B cells and drive B cell proliferation and differentiation. These Th17 cells require B cells for sustained immunit...

🧵1/ New in @Cancer_Cell: Our lab discovered that Th17 cells must team up with B cells to eliminate tumors, and prevent it from coming back.
🔗 Read: www.cell.com/cancer-cell/...
🧬This unexpected immune duo sparks tumor immunity.
🖼️Image: See schematic Th17/B cell antitumor action!

Humoral determinants of checkpoint immunotherapy Nature - Rapid extracellular antibody profiling reveals a contribution of autoantibodies to the effectiveness of checkpoint immunotherapy for cancer.

In this new study, Aaron Ring and colleagues demonstrate the importance of antibody responses on the effectiveness of patients with cancer treated with ICI. As for treatment naive tumors, these are autoandibodies thsat in most cases do not cause autoimmunity:

rdcu.be/exGyT

Microbiota-driven antitumour immunity mediated by dendritic cell migration - Nature A newly identified bacterial strain (YB328) isolated from the faeces of patients who responded to immune checkpoint blockade therapies can promote antitumour immunity through the activation of tumour-...

New insights in @nature.com on how microbiota can drive anti-tumor immunity. It appears that CD103+ CD11b- gut cDCs play a central role in the process. Congrats to the Benno. Y and Nishikawa. H labs 👇
www.nature.com/articles/s41...

Neutrophils drive vascular occlusion, tumour necrosis and metastasis - Nature Neutrophils actively induce tumour necrosis, driving vascular occlusion, pleomorphic necrosis and metastasis.

As a new postdoc in my lab (@cshlnews.bsky.social → @jhu.edu) @adrover.bsky.social (now @crick.ac.uk) saw NETs in tumors—I shrugged. But he looked closer in 3D: NETs block tumor vessels, driving necrosis, hypoxia, EMT & metastasis.
🔗 www.nature.com/articles/s41...
@jhu-bdps.bsky.social @nature.com

Neutrophils drive vascular occlusion, tumour necrosis and metastasis - Nature Neutrophils actively induce tumour necrosis, driving vascular occlusion, pleomorphic necrosis and metastasis.

I’m happy to share our latest work on tumour necrosis! During my time in the @megeblad.bsky.social lab, we found that tumour necrosis is not a passive phenomenon secondary to tumour growth, but an active phenomenon driven by neutrophils and NETs! Thread below: (1/13)
www.nature.com/articles/s41...

NIH announces end to funding for animal-only studies - Drug Discovery and Development Drug Discovery and Development covers strategies and technologies related to pharmaceutical research and development and drug formulation.

Well, this happened yesterday...

www.drugdiscoverytrends.com/nih-announce...

I assume that this pertains only to applications that focus on therapeutic development and not those addressing fundamental biology or mechanism.

But I am wary about making assumptions...

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