Tomorrow, in #PreprintClubHub1 MD Anderson’s Tiantian Zhou will present a #preprint about the way AI-guided CAR designs and AKT3 degradation can synergize to enhance bispecific and trispecific CAR-T cell persistence and overcome #antigen escape. 💻 3️⃣ 🚗

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

Tomorrow, in #PreprintClubHub1 Mount Sinai’s own Yu-Chan Chih will present a #preprint about redirecting cytomegalovirus immunity against pancreatic cancer for immunotherapy. ⤴️🫧🦀

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

Liver transplant rejection features memory cell priming, spatially differentiated networks and novel drug targets Acute T-cell-mediated transplant rejection, the earliest contributor to immunological graft failure responds variably to T-cell suppression. Early rejection can co-exist with donor-specific antibodies...

Tomorrow, in #PreprintClubHub1 Toronto’s own Sai Chung will present a #preprint about the way liver transplant rejection features #memory cell priming, spatially differentiated #networks and novel drug #targets. 🤔 📶 🎯

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

Mutations outside the MR1 antigen binding groove differentially inhibit presentation of exogenous antigens The antigen presenting molecule MHC class I-related protein 1 (MR1) binds small molecule metabolites derived from microbial riboflavin biosynthetic pathways and presents them at the cell surface for s...

Tomorrow, in #PreprintClubHub1 Oxford’s own Anjum Aktar will present a #preprint about the way #mutations outside the MR1 antigen binding groove differentially inhibit presentation of exogenous antigens. 🪩🛑🍽️

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

Alternate isoforms of IRF7 Differentially Regulate Interferon Expression to Tune Response to Viral Infection Interferon Regulatory Factor 7 (IRF7), and its homologue IRF3, are master transcriptional regulators of the innate immune response. IRF7 binds to promoters of interferon β (IFNβ) and several IFNαs as ...

Tomorrow, in #PreprintClubHub1 Mount Sinai’s Rachel Geltman ‪@rachelgeltman.bsky.social will present a #preprint from @asmita_panthi about the way alternate isoforms of IRF7 differentially regulate #interferon expression to tune response to viral infection. 7️⃣ 🎶 🤒

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

Submicron-Sampling of Living Cells by Macrophages An effective immune system must sample and appreciate healthy-self identity to prevent autoimmunity and to contrast to pathogenic insults[1][1]–[3][2]. Self-proteins are presented to T cells in the th...

Tomorrow, in #PreprintClubHub1 Toronto’s own Sara Lamorte will present a #preprint from @amycfanphd.bsky.social & @maxkrummel.bsky.social about submicron-sampling of living cells by #macrophages. 🔍 🤏 🍽️

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

IL-9 as a naturally orthogonal cytokine with optimal JAK/STAT signaling for engineered T cell therapy Arming T cells with a synthetically orthogonal IL-9 receptor (o9R) permits facile engraftment and potent anti-tumor functions. We considered whether the paucity of natural IL-9R expression could be ex...

Tomorrow, in #PreprintClubHub1 Mount Sinai’s Theresa Chu will present a #preprint about the identification of IL-9 as a naturally orthogonal cytokine with optimal JAK/STAT signalling for engineered T cell therapy. 9️⃣ 🎃 👕

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

Neoantigens drive adoptively transferred CD8 T cells to long-lived effectors mediated by lymph node trafficking Adoptive transfer of neoantigen-reactive T lymphocytes mediates potent responses against solid tumors in patients while often limiting toxicity to normal tissues; however, the mechanisms governing the...

Tomorrow, in #PreprintClubHub1 MD Anderson’s own Samuel Andrewes will present a #preprint about #neoantigens driving adoptively transferred CD8 T-cells to long-lived effectors via lymph node trafficking. 🚗 🧓 🚦

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

VISTA-induced tumor suppression by a four amino acid intracellular motif VISTA is a key immune checkpoint receptor under investigation for cancer immunotherapy; however, its signaling mechanisms remain unclear. Here we identify a conserved four amino acid (NPGF) intracellu...

Tomorrow, in #PreprintClubHub1 Karolinska’s Jose Marchan will present a #preprint about VISTA-induced tumour suppression and its mediation via a four amino acid intracellular motif. 🏔️✋4️⃣

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

A pan-cancer atlas of T cell targets T-cell-based immunotherapies have revolutionized cancer treatment, yet only a minority of patients respond to these approaches, significantly constrained by the limited knowledge of tumor-specific ant...

Tomorrow, in #PreprintClubHub1 MD Anderson’s own Ben Shrank will present a #preprint about a pan-cancer T-cell target atlas for the identification of tumour-specific antigens. 🍳 🎯 🌎

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

IL-25-induced memory ILC2s mediate long-term small intestinal adaptation The adaptation of intestinal helminths to vertebrates evolved strategies to attenuate host tissue damage to support reproductive needs of parasites necessary to disseminate offspring to the environmen...

Tomorrow, in #PreprintClubHub1 Mount Sinai’s own Brian Soong will present a #preprint about how IL-25-induced memory group 2 innate lymphoid cells (ILC2s) mediate long-term small intestinal adaptation. 🫧 ⌛ 😋

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

Androgen Signaling in Type 2 Innate Lymphoid Cells Drives Sex Differences in Helicobacter-Induced Gastric Inflammation and Atrophy Background & Aims: Gastric cancer is the fifth most common cancer worldwide. Men are disproportionately affected by gastric cancer, which ranks as the fourth most common cancer in men compared to eigh...

Tomorrow, in #PreprintClubHub1 Toronto’s Miki Gams will present a #preprint from @BusadaLab about how androgen signalling in type 2 innate lymphoid cells drives sex differences in Helicobacter-induced #gastric inflammation and atrophy. 💪🫄🦠

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

A Novel Glia-immune humanized mouse model for investigation of HIV CNS infection and neuroinflammation Although combined antiretroviral therapy (ART) is successful in suppressing viral replication, HIV persists in anatomic reservoirs, including the central nervous system (CNS). Current models, such as ...

Tomorrow, in #PreprintClubHub1 Mount Sinai’s own Aislinn Keane will present a #preprint about a novel glia-immune humanized mouse model for investigation of HIV CNS infection and neuroinflammation. 🐭🧠💊

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

Endogenous antigen processing promotes mRNA vaccine CD4+ T cell responses Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines elicit robust CD4+ T cell responses, which are essential for antiviral immunity. While peptides presented to CD4+ T cells via ma...

Tomorrow, in #PreprintClubHub1 Oxford’s Aleksandra Dzhoneva will present a #preprint about how endogenous antigen processing promotes mRNA vaccine CD4+ T cell responses. 💉🌪️💪

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

Functional memory T cells are derived from exhausted clones and expanded by checkpoint blockade

Tomorrow, in #PreprintClubHub1 MD Anderson’s Annette Wu will present a #preprint from about how functional memory T cells are derived from exhausted clones and expanded by checkpoint blockade. 🥱 🚧📈

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

Also in #PreprintClubHub1 Oxford’s Shannique Clarke will share a #preprint about how macrophages restrict tumour permissiveness to immune infiltration by controlling collagen topography through a Tcf4-Collagen3 fibrotic axis.

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

Tomorrow, in #PreprintClubHub1 Mount Sinai’s Moataz Noureddine will present a #preprint about the way immune aging impairs muscle regeneration via macrophage-derived anti-oxidant selenoprotein P. 💪💪💪

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

IRF7 controls spontaneous autoimmune germinal center and plasma cell checkpoints How IRF7 promotes autoimmune B cell responses and systemic autoimmunity is unclear. Analysis of spontaneous SLE-prone mice deficient in IRF7 uncovered the IRF7 role in regulating autoimmune germinal center (GC), plasma cell (PC) and autoantibody responses and disease. IRF7, however, was dispensable for foreign antigen driven GC, PC and antibody responses. Competitive bone marrow (BM) chimeras highlighted the importance of IRF7 in hematopoietic cells in spontaneous GC and PC differentiation. Single-cell-RNAseq of SLE-prone B cells indicated IRF7 mediated B cell differentiation through GC and PC fates. Mechanistic studies revealed that IRF7 promoted B cell differentiation through GC and PC fates by regulating the transcriptome, translation, and metabolism of SLE-prone B cells. Mixed BM chimeras demonstrated a requirement for B cell-intrinsic IRF7 in IgG autoantibody production but not sufficient for promoting spontaneous GC and PC responses. Altogether, we delineate previously unknown B cell-intrinsic and -extrinsic mechanisms of IRF7-promoted spontaneous GC and PC responses, loss of tolerance, autoantibody production and SLE development. Summary Fike et al. describe previously unknown mechanisms by which IRF7 controls autoimmune B cell and autoantibody responses. Mechanistic studies guided by single-cell-RNAseq and ChIPseq reveal that IRF7 promotes B cell differentiation through germinal center and plasma cell fates by regulating the transcriptome, translation, and metabolism of lupus-prone B cells. ### Competing Interest Statement The authors have declared no competing interest.

Tomorrow, in #PreprintClubHub1 Mount Sinai’s Meredith Ramba will present a #preprint about the way IRF7 controls spontaneous autoimmune germinal centre and plasma cell checkpoints. 7️⃣7️⃣7️⃣

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

A Bi-Specific T Cell-Engaging Antibody Triggers Protective Immune Memory and Glioma Microenvironment Remodeling in Immune Competent Preclinical Models Background Bispecific T cell-engagers (BTEs) are engineered antibodies that redirect T cells to target antigen-expressing tumors. BTEs targeting tumor-specific antigens such as interleukin 13 receptor...

Today, in #PreprintClubHub1 Oxford’s Alfie Carter will present a #preprint about the way a bi-specific T cell-engaging antibody triggers protective immune memory and glioma microenvironment remodelling in immune competent preclinical models. ✌️🧠🐁
www.biorxiv.org/content/10.1...

Tumor-associated macrophages enhance tumor innervation and spinal cord repair Tumor-associated macrophages (TAM) enhance cancer progression by promoting angiogenesis, extracellular matrix (ECM) remodeling, and immune suppression. Nerve infiltration is a hallmark of various canc...

On Wednesday, February 12th, in #PreprintClubHub1 Karolinska’s own Austeja Baleviciute will present a #preprint from about how tumour-associated macrophages enhance tumour innervation and spinal cord repair. 🚧🏗️🛠️

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

Astrocyte-derived MFG-E8 facilitates microglial synapse elimination in Alzheimer’s disease mouse models Region-specific synapse loss is an early pathological hallmark in Alzheimer’s disease (AD). Emerging data in mice and humans highlight microglia, the brain-resident macrophages, as cellular mediators ...

On Wednesday, January 29th, in #PreprintClubHub1 Mount Sinai’s Annie Khamhoung will present a #preprint about how astrocyte-derived MFG-E8 facilitates microglial synapse elimination in #Alzheimer’s disease mouse models. 🧠-🐭-💃
www.biorxiv.org/content/10.1...