A Strong B-cell Response Is Part of the Immune Landscape in Human High-Grade Serous Ovarian Metastases

In high-grade serous ovarian cancer (HGSOC), higher densities of both B cells and the CD8 + T-cell infiltrate were associated with a better prognosis. However, the precise role of B cells in the antitumor response remains unknown. As peritoneal metastases are often responsible for relapse, our aim was to characterize the role of B cells in the antitumor immune response in HGSOC metastases. Unmatched pre and post-chemotherapy HGSOC metastases were studied. B-cell localization was assessed by immunostaining. Their cytokines and chemokines were measured by a multiplex assay, and their phenotype was assessed by flow cytometry. Further in vitro and in vivo assays highlighted the role of B cells and plasma cell IgGs in the development of cytotoxic responses and dendritic cell activation. B cells mainly infiltrated lymphoid structures in the stroma of HGSOC metastases. There was a strong B-cell memory response directed at a restricted repertoire of antigens and production of tumor-specific IgGs by plasma cells. These responses were enhanced by chemotherapy. Interestingly, transcript levels of CD20 correlated with markers of immune cytolytic responses and immune complexes with tumor-derived IgGs stimulated the expression of the costimulatory molecule CD86 on antigen-presenting cells. A positive role for B cells in the antitumor response was also supported by B-cell depletion in a syngeneic mouse model of peritoneal metastasis. Our data showed that B cells infiltrating HGSOC omental metastases support the development of an antitumor response. Clin Cancer Res; 1-13. ©2016 AACR

The UV Continuum Slopes of Early Star-Forming Galaxies in JADES

The power-law slope of the rest-UV continuum ($f_{\lambda}\propto\lambda^{\beta}$) is a key metric of early star forming galaxies, providing one of our only windows into the stellar populations and physical conditions of $z>10$ galaxies. Expanding upon previous studies with limited sample sizes, we leverage deep imaging from JADES to investigate the UV slopes of 179 $z>9$ galaxies with apparent magnitudes of $m_{\rm F200W}=26-31$, which display a median UV slope of $\beta=-2.4$. We compare to a statistical sample of $z=5-9$ galaxies, finding a shift toward bluer rest-UV colors at all $\rm~M_{UV}$. The most UV-luminous $z>9$ galaxies are significantly bluer than their lower-redshift counterparts, representing a dearth of moderately-red galaxies in the first $500~$Myr. At yet earlier times, the $z>11$ galaxy population exhibits very blue UV slopes, implying very low attenuation from dust. We identify a robust sample of 44 galaxies with $\beta<-2.8$, which have SEDs requiring models of density-bounded HII regions and median ionizing photon escape fractions of $0.51$ to reproduce. Their rest-optical colors imply that this sample has weaker emission lines (median $m_{\rm F356W}-m_{\rm F444W}=0.19$ mag) than typical galaxies (median $m_{\rm F356W}-m_{\rm F444W}=0.39$ mag), consistent with the inferred escape fractions. This sample has relatively low stellar masses (median $\log(M/M_{\odot})=7.5$), and specific star-formation rates (median$=79\rm/Gyr$) nearly twice that of our full sample (median$=44\rm/Gyr$), suggesting they are more common among systems experiencing a recent upturn in star formation. We demonstrate that the shutoff of star formation provides an alternative solution for modelling of extremely blue UV colors, making distinct predictions for the rest-optical emission of these galaxies. Future spectroscopy will be required to distinguish between these physical pictures.Comment: 17 pages, 13 figures; submitted to MNRA

The UV continuum slopes of early star-forming galaxies in JADES

© 2024 The Author(s). Published by Oxford University Press on behalf of Royal Astronomical Society. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/The power-law slope of the rest-ultraviolet (UV) continuum (fλ ∝ λβ) is a key metric of early star-forming galaxies, providing one of our only windows into the stellar populations and physical conditions of z ≳ 10 galaxies. Expanding upon previous studies with limited sample sizes, we leverage deep imaging from the JWST Advanced Deep Extragalactic Survey (JADES) to investigate the UV slopes of 179 z ≳ 9 galaxies with apparent magnitudes of mF200W ≃ 26–31, which display a median UV slope of β = −2.4. We compare to a statistical sample of z ≃ 5–9 galaxies, finding a shift towards bluer rest-UV colours at all $M_{\rm UV}$. The most UV-luminous z ≳ 9 galaxies are significantly bluer than their lower redshift counterparts, representing a dearth of moderately red galaxies within the first 500 Myr. At yet earlier times, the z ≳ 11 galaxy population exhibits very blue UV slopes, implying very low impact from dust attenuation. We identify a robust sample of 44 galaxies with β ≲ −2.8, which have spectral energy distributions requiring models of density-bounded H ii regions and median ionizing photon escape fractions of 0.51 to reproduce. Their rest-optical colours imply that this sample has weaker emission lines (median mF356W − mF444W = 0.19 mag) than typical galaxies (median mF356W − mF444W = 0.39 mag), consistent with the inferred escape fractions. This sample consists of relatively low stellar masses (median $\log (M/{\rm M}_{\odot })=7.5\pm 0.2$), and specific star formation rates (sSFRs; median $=79 \, \rm Gyr^{-1}$) nearly twice that of our full galaxy sample (median sSFRs $=44 \, \rm Gyr^{-1}$), suggesting these objects are more common among systems experiencing a recent upturn in star formation. We demonstrate that the shutoff of star formation provides an alternative solution for modelling of extremely blue UV colours, making distinct predictions for the rest-optical emission of these galaxies. Future spectroscopy will be required to distinguish between these physical pictures.Peer reviewe

Detection of Hepatic Drug Metabolite-Specific T-Cell Responses Using a Human Hepatocyte, Immune Cell Coculture System

Drug-responsive T-cells are activated with the parent compound or metabolites, often via different pathways (pharmacological interaction and hapten). An obstacle to the investigation of drug hypersensitivity is the scarcity of reactive metabolites for functional studies and the absence of coculture systems to generate metabolites in situ. Thus, the aim of this study was to utilize dapsone metabolite-responsive T-cells from hypersensitive patients, alongside primary human hepatocytes to drive metabolite formation, and subsequent drug-specific T-cell responses. Nitroso dapsone-responsive T-cell clones were generated from hypersensitive patients and characterized in terms of cross-reactivity and pathways of T-cell activation. Primary human hepatocytes, antigen-presenting cells, and T-cell cocultures were established in various formats with the liver and immune cells separated to avoid cell contact. Cultures were exposed to dapsone, and metabolite formation and T-cell activation were measured by LC-MS and proliferation assessment, respectively. Nitroso dapsone-responsive CD4+ T-cell clones from hypersensitive patients were found to proliferate and secrete cytokines in a dose-dependent manner when exposed to the drug metabolite. Clones were activated with nitroso dapsone-pulsed antigen-presenting cells, while fixation of antigen-presenting cells or omission of antigen-presenting cells from the assay abrogated the nitroso dapsone-specific T-cell response. Importantly, clones displayed no cross-reactivity with the parent drug. Nitroso dapsone glutathione conjugates were detected in the supernatant of hepatocyte immune cell cocultures, indicating that hepatocyte-derived metabolites are formed and transferred to the immune cell compartment. Similarly, nitroso dapsone-responsive clones were stimulated to proliferate with dapsone, when hepatocytes were added to the coculture system. Collectively, our study demonstrates the use of hepatocyte immune cell coculture systems to detect in situ metabolite formation and metabolite-specific T-cell responses. Similar systems should be used in future diagnostic and predictive assays to detect metabolite-specific T-cell responses when synthetic metabolites are not available

The Star-forming and Ionizing Properties of Dwarf z~6-9 Galaxies in JADES: Insights on Bursty Star Formation and Ionized Bubble Growth

Reionization is thought to be driven by faint star-forming galaxies, but characterizing this population in detail has long remained very challenging. Here we utilize deep nine-band NIRCam imaging from JADES to study the star-forming and ionizing properties of 756 $z\sim6-9$ galaxies, including hundreds of very UV-faint objects ($M_\mathrm{UV}>-18$). The faintest ($m\sim30$) galaxies in our sample typically have stellar masses of $M_\ast\sim(1-3)\times10^7$ $M_\odot$ and young light-weighted ages ($\sim$50 Myr), though some show strong Balmer breaks implying much older ages ($\sim$500 Myr). We find no evidence for extremely massive galaxies ($>3\times10^{10}$ $M_\odot$) in our sample. We infer a strong (factor $>$2) decline in the typical [OIII]$+$H$\beta$ EWs towards very faint $z\sim6-9$ galaxies, yet a weak UV luminosity dependence on the H$\alpha$ EWs at $z\sim6$. We demonstrate that these EW trends can be explained if fainter galaxies have systematically lower metallicities as well as more recently-declining star formation histories relative to the most UV-luminous galaxies in our sample. Our data provide evidence that the brightest galaxies are frequently experiencing a recent strong upturn in SFR. We also discuss how the EW trends may be influenced by a strong correlation between $M_\mathrm{UV}$ and Lyman continuum escape fraction. This alternative explanation has dramatically different implications for the contribution of galaxies along the luminosity function to cosmic reionization, highlighting the need for deep spectroscopic follow-up. Finally, we quantify the photometric overdensities around two $z>7$ strong Ly$\alpha$ emitters in the JADES footprint. One Ly$\alpha$ emitter lies close to a strong photometric overdensity while the other shows no significant nearby overdensity, perhaps implying that not all strong $z>7$ Ly$\alpha$ emitters reside in large ionized bubbles.Comment: 29 pages, 16 figures. Submitted to MNRAS. Comments welcom

The Cosmos in its Infancy: JADES Galaxy Candidates at z > 8 in GOODS-S and GOODS-N

© 2024. The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by/4.0/We present a catalog of 717 candidate galaxies at z > 8 selected from 125 square arcmin of NIRCam imaging as part of the JWST Advanced Deep Extragalactic Survey (JADES). We combine the full JADES imaging data set with data from the JWST Extragalactic Medium Survey and First Reionization Epoch Spectroscopic COmplete Survey (FRESCO) along with extremely deep existing observations from Hubble Space Telescope (HST)/Advanced Camera for Surveys (ACS) for a final filter set that includes 15 JWST/NIRCam filters and five HST/ACS filters. The high-redshift galaxy candidates were selected from their estimated photometric redshifts calculated using a template-fitting approach, followed by visual inspection from seven independent reviewers. We explore these candidates in detail, highlighting interesting resolved or extended sources, sources with very red long-wavelength slopes, and our highest-redshift candidates, which extend to z phot ∼ 18. Over 93% of the sources are newly identified from our deep JADES imaging, including 31 new galaxy candidates at z phot > 12. We also investigate potential contamination by stellar objects, and do not find strong evidence from spectral energy distribution fitting that these faint high-redshift galaxy candidates are low-mass stars. Using 42 sources in our sample with measured spectroscopic redshifts from NIRSpec and FRESCO, we find excellent agreement to our photometric redshift estimates, with no catastrophic outliers and an average difference of 〈Δz = z phot − z spec〉 = 0.26. These sources comprise one of the most robust samples for probing the early buildup of galaxies within the first few hundred million years of the Universe’s history.Peer reviewe

The Cosmos in its Infancy: JADES Galaxy Candidates at z > 8 in GOODS-S and GOODS-N

We present a catalog of 717 candidate galaxies at $z > 8$ selected from 125 square arcminutes of NIRCam imaging as part of the JWST Advanced Deep Extragalactic Survey (JADES). We combine the full JADES imaging dataset with data from the JEMS and FRESCO JWST surveys along with extremely deep existing observations from HST/ACS for a final filter set that includes fifteen JWST/NIRCam filters and five HST/ACS filters. The high-redshift galaxy candidates were selected from their estimated photometric redshifts calculated using a template fitting approach, followed by visual inspection from seven independent reviewers. We explore these candidates in detail, highlighting interesting resolved or extended sources, sources with very red long-wavelength slopes, and our highest redshift candidates, which extend to $z_{phot} = 18$. We also investigate potential contamination by stellar objects, and do not find strong evidence from SED fitting that these faint high-redshift galaxy candidates are low-mass stars. Over 93\% of the sources are newly identified from our deep JADES imaging, including 31 new galaxy candidates at $z_{phot} > 12$. Using 42 sources in our sample with measured spectroscopic redshifts from NIRSpec and FRESCO, we find excellent agreement to our photometric redshift estimates, with no catastrophic outliers and an average difference of $\langle \Delta z = z_{phot}- z_{spec} \rangle= 0.26$. These sources comprise one of the most robust samples for probing the early buildup of galaxies within the first few hundred million years of the Universe's history.Comment: v2: 40 pages, 18 figures, submitted to AAS Journals, online data catalog (JADES Deep only) found at https://doi.org/10.5281/zenodo.809252

JADES Imaging of GN-z11: Revealing the Morphology and Environment of a Luminous Galaxy 430 Myr After the Big Bang

We present JWST NIRCam 9-band near-infrared imaging of the luminous $z=10.6$ galaxy GN-z11 from the JWST Advanced Deep Extragalactic Survey (JADES) of the GOODS-N field. We find a spectral energy distribution (SED) entirely consistent with the expected form of a high-redshift galaxy: a clear blue continuum from 1.5 to 4 microns with a complete dropout in F115W. The core of GN-z11 is extremely compact in JWST imaging. We analyze the image with a two-component model, using a point source and a S\'{e}rsic profile that fits to a half-light radius of 200 pc and an index $n=0.9$. We find a low-surface brightness haze about $0.4''$ to the northeast of the galaxy, which is most likely a foreground object but might be a more extended component of GN-z11. At a spectroscopic redshift of 10.60 (Bunker et al. 2023), the comparison of the NIRCam F410M and F444W images spans the Balmer jump. From population synthesis modeling, here assuming no light from an active galactic nucleus, we reproduce the SED of GN-z11, finding a stellar mass of $\sim$$10^{9}~M_{\odot}$, a star-formation rate of $\sim$$20~M_{\odot}~\mathrm{yr}^{-1}$ and a young stellar age of $\sim$$20~\mathrm{Myr}$. As massive galaxies at high redshift are likely to be highly clustered, we search for faint neighbors of GN-z11, finding 9 galaxies out to $\sim$5 comoving Mpc transverse with photometric redshifts consistent with $z=10.6$, and a 10$^{\rm th}$ more tentative dropout only $3''$ away.Comment: Submitted to ApJ; 18 pages, 8 figures; comments welcom

Spectroscopy of four metal-poor galaxies beyond redshift ten

Finding and characterising the first galaxies that illuminated the early Universe at cosmic dawn is pivotal to understand the physical conditions and the processes that led to the formation of the first stars. In the first few months of operations, imaging from the James Webb Space Telescope (JWST) have been used to identify tens of candidates of galaxies at redshift (z) greater than 10, less than 450 million years after the Big Bang. However, none of these candidates has yet been confirmed spectroscopically, leaving open the possibility that they are actually low-redshift interlopers. Here we present spectroscopic confirmation and analysis of four galaxies unambiguously detected at redshift 10.3<z<13.2, previously selected from NIRCam imaging. The spectra reveal that these primeval galaxies are extremely metal poor, have masses between 10^7 and a few times 10^8 solar masses, and young ages. The damping wings that shape the continuum close to the Lyman edge are consistent with a fully neutral intergalactic medium at this epoch. These findings demonstrate the rapid emergence of the first generations of galaxies at cosmic dawn.Comment: 32 pages, 9 figures, Submitte

JADES Initial Data Release for the Hubble Ultra Deep Field: Revealing the Faint Infrared Sky with Deep JWST NIRCam Imaging

© 2023. The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/JWST has revolutionized the field of extragalactic astronomy with its sensitive and high-resolution infrared view of the distant Universe. Adding to the new legacy of JWST observations, we present the first NIRCam imaging data release from the JWST Advanced Deep Extragalactic Survey (JADES), providing nine filters of infrared imaging of ∼25 arcmin2 covering the Hubble Ultra Deep Field and portions of Great Observatories Origins Deep Survey South. Utilizing 87 on-sky dual-filter hours of exposure time, these images reveal the deepest ever near-infrared view of this iconic field. We supply carefully constructed nine-band mosaics of the JADES bands, as well as matching reductions of five additional bands from the JWST Extragalactic Medium-band Survey. Combining with existing Hubble Space Telescope imaging, we provide 23-band space-based photometric catalogs and photometric redshifts for ≈47,500 sources. To promote broad engagement with JADES, we have created an interactive FitsMap website to provide an interface for professional researchers and the public to experience these JWST data sets. Combined with the first JADES NIRSpec data release, these public JADES imaging and spectroscopic data sets provide a new foundation for discoveries of the infrared Universe by the worldwide scientific community.Peer reviewe