Featured
-
-
Article
| Open AccessPharmaceutical targeting of OTUB2 sensitizes tumors to cytotoxic T cells via degradation of PD-L1
PD-L1 expression on the surface of cancer cells is believed to contribute to tumor immune evasion via triggering the inhibitory T cell co-receptor, PD-1, resulting in decreased T cell cytotoxicity. Here authors show that OTUB2 regulates PD-L1 expression via inhibition of its ubiquitin-mediated degradation, and that OTUB2 inhibition increases T cell cytotoxicity directed against tumors.
- Wenfeng Ren
- , Zilong Xu
- & Ningshao Xia
-
Article
| Open AccessFOXP3+ regulatory T cell perturbation mediated by the IFNγ-STAT1-IFITM3 feedback loop is essential for anti-tumor immunity
Modulation of regulatory T cells (Treg) in the tumour environment is a potential avenue to bolster anti-tumor immunity. Here Liu et al show that perturbation of the negative feedback loop involving STAT1- IFITM3 influences anti-tumor immunity, and that IFITM3 or STAT1 deficiency resulting in the fragility of tumor-infiltrating Treg cells.
- Xinnan Liu
- , Weiqi Zhang
- & Bin Li
-
Article
| Open AccessItaconate promotes hepatocellular carcinoma progression by epigenetic induction of CD8+ T-cell exhaustion
Itaconate is an immunomodulatory metabolite that has been reported to regulate tumorigenesis. Here, the authors show that macrophage-derived itaconate induces epigenetic-mediated CD8+ T cell exhaustion, promoting hepatocellular carcinoma development.
- Xuemei Gu
- , Haoran Wei
- & Ping Gao
-
Article
| Open AccessLow-dose radiotherapy combined with dual PD-L1 and VEGFA blockade elicits antitumor response in hepatocellular carcinoma mediated by activated intratumoral CD8+ exhausted-like T cells
An increasing number of preclinical and clinical studies have investigated the antitumor efficacy of combined radiotherapy and immunotherapy. Here the authors report that low-dose radiotherapy enhances the antitumor effect of dual VEGFA and PD-L1 blockade in preclinical models of hepatocellular carcinoma.
- Siqi Li
- , Kun Li
- & Yang Yang
-
Article
| Open AccessID1 expressing macrophages support cancer cell stemness and limit CD8+ T cell infiltration in colorectal cancer
Inhibitor of differentiation 1 (ID1) has been described as a cancer-promoting factor and also involved in the formation of an immunosuppressive tumor microenvironment. Here the authors report that ID1-expressing tumor associated macrophages favor colorectal cancer progression by promoting cancer cell stemness and CD8+ T cell exclusion.
- Shuang Shang
- , Chen Yang
- & Fang Hua
-
Article
| Open AccessA distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing
γδ T cells are known to recognize phosphoantigen in the context of butyrophilins (BTN), yet the molecular rules underlying this phenomenon are unclear. Here, the authors demonstrate that a distinct topology of B30.2 and IgV domains within BTN3A complexes promotes antigen sensing and that the juxtamembrane region controls BTN complex formation.
- Mohindar M. Karunakaran
- , Hariharan Subramanian
- & Thomas Herrmann
-
Article
| Open AccessGut microbial structural variation associates with immune checkpoint inhibitor response
Here, using datasets from the gut microbiome of 996 patients from seven clinical trials, the authors characterize gut microbial genomic structural variants, located in species such as Akkermansia muciniphila, Dorea formicigenerans, and Bacteroides caccae, that associate with hosts’ response and survival after immune checkpoint inhibitors treatment.
- Rong Liu
- , You Zou
- & Dao-Ming Wang
-
Article
| Open AccessNanomedicine-based co-delivery of a calcium channel inhibitor and a small molecule targeting CD47 for lung cancer immunotherapy
Lung cancer is characterized by an immunosuppressive microenvironment, limiting responses to immunotherapies. Here the authors report the design of a pH-responsive nanomedicine for the co-delivery of a T-type calcium channel inhibitor and of a small molecule targeting CD47, promoting anti-tumor immune responses in orthotopic lung cancer preclinical models.
- Yuedong Guo
- , Qunqun Bao
- & Jianlin Shi
-
Article
| Open AccessUnlocking the potential of allogeneic Vδ2 T cells for ovarian cancer therapy through CD16 biomarker selection and CAR/IL-15 engineering
Vγ9Vδ2 (Vδ2) T cells have been proposed as cell carriers for off-the-shelf CAR therapies. Here the authors describe CD16 as a biomarker for the selection of Vδ2 T cells with high levels of cytotoxicity and report the anti-tumor activity of engineered CD16high Vδ2 T cells in ovarian cancer preclinical models.
- Derek Lee
- , Zachary Spencer Dunn
- & Lili Yang
-
Article
| Open AccessImmuno-metabolic dendritic cell vaccine signatures associate with overall survival in vaccinated melanoma patients
Efficacy of dendritic cell (DC)-based vaccines remains unsatisfactory. Here the authors analyse the transcriptomic and immune-metabolic profiles of DCs from patients enrolled in a DC vaccine trial in late-stage melanoma, suggesting that the metabolic profile of DC is associated with the immunostimulatory potential of the cancer vaccine.
- Juraj Adamik
- , Paul V. Munson
- & Lisa H. Butterfield
-
Article
| Open AccessImmunological and clinicopathological features predict HER2-positive breast cancer prognosis in the neoadjuvant NeoALTTO and CALGB 40601 randomized trials
Neoadjuvant therapies with dual anti-HER2 blockade have proven effective in HER2+ breast cancer treatment. Here, the authors develop a score that integrates antigen receptor repertoire features and clinical parameters to predict prognosis after anti-HER2 neoadjuvant treatments.
- Mattia Rediti
- , Aranzazu Fernandez-Martinez
- & Christos Sotiriou
-
Article
| Open AccessA2AR eGFP reporter mouse enables elucidation of A2AR expression dynamics during anti-tumor immune responses
Adenosine is an immunosuppressive metabolite known to limit anti-tumor immune responses. Here the authors report the characterization of an adenosine A2A receptor (A2AR) eGFP reporter mouse, providing immunological insights into the biology of A2AR expression in the context of anti-tumor immunity.
- Kirsten L. Todd
- , Junyun Lai
- & Paul A. Beavis
-
Article
| Open AccessA tuft cell - ILC2 signaling circuit provides therapeutic targets to inhibit gastric metaplasia and tumor development
Within gastrointestinal tissues, tuft cells, a rare population of chemo-sensory epithelial cells, can promote the activation of type 2 innate lymphoid cells (ILC2s). Here the authors show that tuft cells and ILC2s are increased during gastric cancer development and that the pharmacologic inhibition of tuft cell derived IL25 or ILC2-produced IL13 reduces gastric tumor growth.
- Ryan N. O’Keefe
- , Annalisa L. E. Carli
- & Michael Buchert
-
Article
| Open AccessMicrophysiological model reveals the promise of memory-like natural killer cell immunotherapy for HIV± cancer
Current biological models for examining cancer immunobiology in a HIV infected context are lacking. Here the authors use a human-derived microphysiological model to represent the HIV immune system and assess the ability of transferred populations of NK cells in the targeting of tumours.
- Jose M. Ayuso
- , Mehtab Farooqui
- & David J. Beebe
-
Article
| Open AccessKupffer cells prevent pancreatic ductal adenocarcinoma metastasis to the liver in mice
The liver is the most common site of metastasis for pancreatic ductal adenocarcinoma (PDAC). Here, the authors demonstrate that β-glucan, a microbial component associated with trained immunity, activates liver-resident macrophages (Kupffer cells) and prevents PDAC metastasis to the liver
- Stacy K. Thomas
- , Max M. Wattenberg
- & Gregory L. Beatty
-
Article
| Open AccessRepressed Blautia-acetate immunological axis underlies breast cancer progression promoted by chronic stress
Chronic stress can promote breast cancer progression. Here the authors show that a reduction in the levels of Blautia and its metabolite acetate contributes to chronic stress-promoted breast cancer progression, associated with decreased CD8 + T cell anti-tumor immunity.
- Ling Ye
- , Yuanlong Hou
- & Haiping Hao
-
Article
| Open AccessModulation of lytic molecules restrain serial killing in γδ T lymphocytes
γδ T cells are unique T lymphocytes with cytotoxic functions, targeting infections and tumours. Here authors show that the target killing function of γδ T cells is tightly regulated at the level of the availability of lytic molecules granzyme B and perforin.
- Patrick A. Sandoz
- , Kyra Kuhnigk
- & Björn Önfelt
-
Article
| Open AccessPARP14 inhibition restores PD-1 immune checkpoint inhibitor response following IFNγ-driven acquired resistance in preclinical cancer models
IFNγ signalling has been described as a potential driver of resistance to immune checkpoint blockade (ICB) therapy. Here the authors report that PARP14 is upregulated in chronic IFNγ-treated cancer cell models and that its inhibition restores response to anti-PD-1 therapy in preclinical cancer models.
- Chun Wai Wong
- , Christos Evangelou
- & Adam F. L. Hurlstone
-
Article
| Open AccessLarge T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance
Myelomagenesis progresses through well-defined pre-malignant states. Here, using single-cell RNA sequencing and T cell receptor repertoire analysis of bone marrow T cells in patients at different stages of myelomagenesis, the authors identify large clonotypic expansions characterized by the expression of multiple immune checkpoints.
- Cirino Botta
- , Cristina Perez
- & Bruno Paiva
-
Article
| Open AccessThe tumor microenvironment shows a hierarchy of cell-cell interactions dominated by fibroblasts
The tumor microenvironment (TME) is complex and heterogenous, with cancer cells and diverse non-malignant cells interacting with each other. Here the authors define the network of interactions between different cell types in the TME of breast cancer, identifying and characterizing a two-cell circuit of cancer associated fibroblasts and macrophages.
- Shimrit Mayer
- , Tomer Milo
- & Ruth Scherz-Shouval
-
Article
| Open AccessActivation of melanocortin-1 receptor signaling in melanoma cells impairs T cell infiltration to dampen antitumor immunity
Aberrant G protein-coupled receptor (GPCR) signaling has been associated with tumor progression and metastasis. Here the authors show that depletion of the GPCR melanocortin-1 receptor (MC1R) in melanoma cells is associated with enhanced T cell infiltration and anti-tumor immune responses.
- Yazhong Cui
- , Yang Miao
- & Ting Han
-
Article
| Open AccessStressed target cancer cells drive nongenetic reprogramming of CAR T cells and solid tumor microenvironment
The emergency of a high frequency of early memory T cells has been associated with clinical success of CAR T cell therapy. Here the authors show that target cancer cells stressed by disulfiram/copper complexes and ionizing radiation favour the reprogramming of CAR T cells that acquire memory-like characteristics, associated with prolonged anti-tumor response in preclinical solid tumor models.
- Yufeng Wang
- , David L. Drum
- & Xinhui Wang
-
Article
| Open AccessCell microparticles loaded with tumor antigen and resiquimod reprogram tumor-associated macrophages and promote stem-like CD8+ T cells to boost anti-PD-1 therapy
Tumor associated macrophages (TAMs) contribute to the immunosuppressive tumor microenvironment, including hepatocellular carcinoma (HCC). Here the authors show that macrophage-derived microparticles modified with a M2-like macrophage targeting peptide and loaded with the TLR7/8 agonist resiquimod reprogram TAMs from immunosuppressive to inflammatory, promoting anti-tumor immune responses in preclinical HCC models.
- Xiaoqiong Zhang
- , Zhaohan Wei
- & Lu Gan
-
Article
| Open AccessLet-7 enhances murine anti-tumor CD8 T cell responses by promoting memory and antagonizing terminal differentiation
Effective CD8+ T cell immunity requires the generation of a long-lived memory pool and the maintenance of a non-exhausted effector T cell pool. The implementation of immune checkpoint blockade can reduced levels of exhaustion but lacks the ability to support memory formation in the effector pool. Here the authors suggest a role for Let-7 in the enhancement of the anti-tumor CD8+ T cell response by supporting memory via modulation of metabolic and differentiation state.
- Alexandria C. Wells
- , Kaito A. Hioki
- & Leonid A. Pobezinsky
-
Article
| Open AccessAtezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial
Stereotactic ablative radiotherapy (SABR) is standard-of-care for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC), however the risk of systemic recurrences remains high. Here the authors report the results of a phase I study testing the addition of atezolizumab (anti-PD-L1) to SABR in high risk, medically inoperable, early-stage, NSCLC.
- Arta M. Monjazeb
- , Megan E. Daly
- & Karen Kelly
-
Article
| Open AccessLow-dose carboplatin modifies the tumor microenvironment to augment CAR T cell efficacy in human prostate cancer models
Although CAR T therapy has greatly improved the therapeutic prospects for haematological malignancies, it is not yet widely used for solid tumors, such as prostate cancer. Here, using prostate cancer patient-derived xenografts, the authors demonstrate the efficacy of CAR T cells specific for Lewis Y antigen when combined with low-dose carboplatin.
- L. H. Porter
- , J. J. Zhu
- & G. P. Risbridger
-
Article
| Open AccessImmunotherapy targeting different immune compartments in combination with radiation therapy induces regression of resistant tumors
Radiation therapy (RT) has been shown to improve responses to immunotherapy in preclinical cancer models, but deep responses in patients are still rare. Here the authors provide immunological insights into the response to RT and CTLA4 inhibition in tumor bearing mice and show that agonistic CD40 therapy improves response to the combination of RT and immune checkpoint inhibition.
- Nils-Petter Rudqvist
- , Maud Charpentier
- & Sandra Demaria
-
Article
| Open AccessNeoadjuvant sintilimab in combination with concurrent chemoradiotherapy for locally advanced gastric or gastroesophageal junction adenocarcinoma: a single-arm phase 2 trial
Neoadjuvant chemotherapy followed by gastrectomy is considered standard of care for locally advanced gastric and gastroesophageal junction (G/GEJ) cancers. Here the authors report the results of a phase 2 trial of neoadjuvant sintilimab (anti-PD1) plus chemoradiotherapy in patients with locally advanced G/GEJ tumors.
- Jia Wei
- , Xiaofeng Lu
- & Baorui Liu
-
Article
| Open AccessCamrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial
Combination of immune checkpoint inhibitors with anti-angiogenic targeted therapy has shown efficacy in some solid tumours. Here the authors report the results of a phase 2 trial of camrelizumab (anti-PD1) plus apatinib as a second-line or later-line treatment regimen in platinum-resistant (cohort 1) or PD-1 inhibitor-resistant (cohort 2) Recurrent/Metastatic Nasopharyngeal Carcinoma patients.
- Li Yuan
- , Guo-Dong Jia
- & Hai-Qiang Mai
-
Article
| Open AccessA synthetic metastatic niche reveals antitumor neutrophils drive breast cancer metastatic dormancy in the lungs
3D scaffolds can be used to recapitulate key aspects of the microenvironment of primary tumors and metastatic organs. Here the authors use subcutaneous porous 3D scaffold implants as a tool to study the immune signals in the lungs of metastatic breast cancer, revealing multifaceted roles of neutrophils in regulating lung metastasis.
- Jing Wang
- , Ramon Ocadiz-Ruiz
- & Lonnie D. Shea
-
Article
| Open AccessA multiplex blood-based assay targeting DNA methylation in PBMCs enables early detection of breast cancer
DNA methylation pattern of immune cells can be altered during tumour development. Here, the authors identify 4 DNA methylation markers in peripheral blood mononuclear cells which are predictive of breast cancer across multiple cohorts.
- Tiantian Wang
- , Peilong Li
- & Chuanxin Wang
-
Article
| Open AccessCombined PD-L1/TGFβ blockade allows expansion and differentiation of stem cell-like CD8 T cells in immune excluded tumors
It has been previously shown that combining immune checkpoint inhibitors with TGFβ blockade potentiates anti-tumor immune responses. Here the authors show that, in an immune excluded preclinical tumor model, combining therapeutic anti-PD-L1 with anti-TGFβ treatment promotes expansion and differentiation of stem-cell like CD8 + T cells.
- Alessandra Castiglioni
- , Yagai Yang
- & Sören Müller
-
Article
| Open AccessProteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification
RNA variants derived from cancer-associated RNA editing events can be a source of neoantigens. Here, based on a proteogenomic pipeline combining DNA and RNA sequencing with MS-based immunopeptidomics, the authors identity and validate potential neoantigen candidates in patients with different tumor entities, highlighting RNA as important neoantigen source.
- Celina Tretter
- , Niklas de Andrade Krätzig
- & Angela M. Krackhardt
-
Article
| Open AccessChemically programmed STING-activating nano-liposomal vesicles improve anticancer immunity
Agonists of the cytosolic DNA-sensing STING pathway potently remodel the tumour immune microenvironment to support anti-tumour adaptive immunity, but at the expense of adverse systemic inflammation. Here authors exchange the STING agonist MSA-2 with its prodrugs that are suitable for nano-liposomal delivery and thus achieve increased efficiency and decreased toxicity.
- Xiaona Chen
- , Fanchao Meng
- & Hangxiang Wang
-
Article
| Open AccessA small molecule inhibitor of PTP1B and PTPN2 enhances T cell anti-tumor immunity
Here, the authors demonstrate that inhibition of PTP1B and PTPN2 in tumor cells and T-cells with a small molecule inhibitor represses the growth of immunogenic and cold tumors, and enhances response to anti-PD-1 immunotherapy without promoting immune-related toxicities.
- Shuwei Liang
- , Eric Tran
- & Tony Tiganis
-
Article
| Open AccessSafety and anti-tumour activity of the IgE antibody MOv18 in patients with advanced solid tumours expressing folate receptor-alpha: a phase I trial
IgE antibodies have shown anti-tumor activity, even superior to IgG, in preclinical models. However, all monoclonal antibodies in clinical use for cancer therapy are members of the IgG class. Here the authors report the results of a phase I clinical trial of a chimeric monoclonal IgE antibody, specific for the folate receptor-alpha, in patients with advanced solid cancer.
- James Spicer
- , Bristi Basu
- & Sophia N. Karagiannis
-
Article
| Open AccessOncolytic viruses engineered to enforce cholesterol efflux restore tumor-associated macrophage phagocytosis and anti-tumor immunity in glioblastoma
Glioblastoma (GBM) cells are metabolically dependent on exogenous cholesterol uptake and targeting cholesterol metabolism has been proposed as a therapeutic option for GBM. Here the authors show that cholesterol promotes phagocytic dysfunction in tumor associated macrophages and they develop an Apo-A1 armed oncolytic adenovirus restoring anti-tumor immunity in GBM preclinical models.
- Wang Shiqun
- , Yan Wei
- & Wei Jiwu
-
Article
| Open AccessTumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment
Here authors show that GDF15, a cytokine that is produced by cancer cells, prevents T cells from extravasation into the tumour microenvironment. Low availability of T cells in GDF-15-expressing tumours thus precludes effective immune therapy.
- Markus Haake
- , Beatrice Haack
- & Jörg Wischhusen
-
Article
| Open AccessCellSighter: a neural network to classify cells in highly multiplexed images
Identification and classification of cells in multiplexed microscopy remain challenging. Here, the authors propose CellSighter, which uses neural networks to perform cell classification directly on multiplexed images, thus leveraging the spatial expression characteristics of proteins.
- Yael Amitay
- , Yuval Bussi
- & Leeat Keren
-
Article
| Open AccessIL1R1+ cancer-associated fibroblasts drive tumor development and immunosuppression in colorectal cancer
IL1 signalling pathway has been shown to shape cancer associated fibroblast (CAF) heterogeneity. Here the authors identify a pro-tumorigenic CAF subtype in colorectal cancer characterized by high IL1R1 expression and associated with an immunosuppressive tumor microenvironment.
- E. Koncina
- , M. Nurmik
- & E. Letellier
-
Article
| Open AccessLoss of PHF8 induces a viral mimicry response by activating endogenous retrotransposons
The role of PHD finger protein 8 (PHF8) in anti-tumour immunity remains to be investigated. Here, the authors suggest PHF8 as an epigenetic checkpoint and show that targeting PHF8 induces a viral mimicry response enhancing anti-tumour immunity in colorectal cancer.
- Yanan Liu
- , Longmiao Hu
- & Xiufeng Pang
-
Article
| Open AccessARIH1 activates STING-mediated T-cell activation and sensitizes tumors to immune checkpoint blockade
Loss of the E3 ubiquitin-protein ligase ARIH1 has been associated with cancer escape from anti-tumor immunity. Here the authors show that ARIH1 mediated ubiquitination and degradation of DNA-PKcs trigger activation of STING pathway in tumor cells, sensitizing tumors to immune checkpoint blockade.
- Xiaolan Liu
- , Xufeng Cen
- & Hongguang Xia
-
Article
| Open AccessMolecular mechanism of phosphopeptide neoantigen immunogenicity
Phosphorylated peptide antigens are present on cancer cells, but their role in cancer immunity is unknown. Here, the authors describe a molecular mechanism, by which a tumor-specific phosphopeptide found in acute myeloid leukemia is recognized by the human immune T cells.
- Yury Patskovsky
- , Aswin Natarajan
- & Michelle Krogsgaard
-
Article
| Open AccessNivolumab plus chemoradiotherapy in locally-advanced cervical cancer: the NICOL phase 1 trial
A combination of chemoradiotherapy followed by brachytherapy is recommended for patients with locally-advanced cervical cancer (LACC), however there is still a high risk of disease recurrence. Here the authors report clinical outcomes and immunologic correlates of a clinical trial of the PD-1 inhibitor nivolumab in combination with chemoradiotherapy in LACC patients.
- Manuel Rodrigues
- , Giulia Vanoni
- & Emanuela Romano
-
Article
| Open AccessA pilot study of lymphodepletion intensity for peripheral blood mononuclear cell-derived neoantigen-specific CD8 + T cell therapy in patients with advanced solid tumors
The majority of adoptive T cell therapy-based clinical studies are based on the ex vivo expansion of neoantigen-specific tumor infiltrating lymphocytes. Here the authors report the results of a pilot study of adoptive cell therapy with personalized neoantigen-specific CD8 + T cells obtained from peripheral blood mononuclear cells in patients with locally advanced or metastatic solid tumors refractory.
- Dandan Li
- , Chao Chen
- & Rui-Hua Xu
-
Article
| Open AccessB cell profiles, antibody repertoire and reactivity reveal dysregulated responses with autoimmune features in melanoma
B cells are playing an active role in shaping the tumour immune microenvironment and the anti-tumour immune response in melanomas. Here authors show that intra-tumoral B cells are aberrantly activated and produce antibodies that are potentially autoreactive.
- Silvia Crescioli
- , Isabel Correa
- & Sophia N. Karagiannis
-
Article
| Open AccessNeoantigen-specific CD8 T cells with high structural avidity preferentially reside in and eliminate tumors
Tumor neoantigens versus tumor-associated antigens may have different functions in antitumor immunity depending on the strength of antigen recognition. Here the authors characterize CD8 T cell clones specific for TAA, neoantigens or viral antigens isolated from tumor and blood and show that neoantigen-specific clones have a higher structural avidity than TAA-specific ones and preferentially infiltrate tumors.
- Julien Schmidt
- , Johanna Chiffelle
- & Alexandre Harari
-
Article
| Open AccessEvaluation of therapeutic PD-1 antibodies by an advanced single-molecule imaging system detecting human PD-1 microclusters
Immune checkpoint inhibitors are now routinely used in cancer therapy, however, the dosage and integration into conventional cancer therapy is determined via empirical experience rather than mechanistic rationale. Here authors establish an advanced single-molecule imaging method, by with which they are directly monitoring and evaluating the effect of immune checkpoint inhibitors on T cell signaling.
- Wataru Nishi
- , Ei Wakamatsu
- & Tadashi Yokosuka
-
Article
| Open AccessLysophosphatidic acid modulates CD8 T cell immunosurveillance and metabolism to impair anti-tumor immunity
Lysophosphatidic acid is known to increase in concentration in multiple cancer types. Here, the authors show it affects CD8 T cell metabolism, phenotype, and effector functions, and plasma concentrations appear predictive of response to immunotherapy.
- Jacqueline A. Turner
- , Malia A. Fredrickson
- & Raul M. Torres