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Author Scott I Abrams

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Overcoming primary and acquired resistance to anti-PD-L1 therapy by induction and activation of tumor-residing cDC1s.

Takaaki Oba, Mark D Long, Tibor Keler, Henry C Marsh, Hans Minderman, Scott I Abrams, Song Liu, Fumito Ito,

The ability of cancer cells to ensure T-cell exclusion from the tumor microenvironment is a significant mechanism of resistance to anti-PD-1/PD-L1 therapy. Evidence indicates crucial roles of Batf3-dependent conventional type-1 dendritic cells (cDC1s) for inducing antitumor T-cell immunity; however, strategies to maximize cDC1 engagement remain elusive. Here, using multiple orthotopic ... Read more >>

Nat Commun (Nature communications)
[2020, 11(1):5415]

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Radiation induces dynamic changes to the T cell repertoire in renal cell carcinoma patients.

Jacky Chow, Nicholas C Hoffend, Scott I Abrams, Thomas Schwaab, Anurag K Singh, Jason B Muhitch,

Clinical studies combining radiation and immunotherapy have shown promising response rates, strengthening efforts to sensitize tumors to immune-mediated attack. Thus, there is an ongoing surge in trials using preconditioning regimens with immunotherapy. Yet, due to the scarcity of resected tumors treated in situ with radiotherapy, there has been little investigation ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2020, 117(38):23721-23729]

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Circulating CD14+ HLA-DRlo/- monocytic cells as a biomarker for epithelial ovarian cancer progression.

Ashley E Stenzel, Scott I Abrams, Janine M Joseph, Ellen L Goode, Joseph D Tario, Paul K Wallace, Divjot Kaur, Anna-Kay Adamson, Matthew F Buas, Amit A Lugade, Angela Laslavic, Sarah E Taylor, Brian Orr, Robert P Edwards, Esther Elishaev, Kunle Odunsi, Jennifer M Mongiovi, John Lewis Etter, Stacey J Winham, Scott H Kaufmann, Francesmary Modugno, Kirsten B Moysich,

PROBLEM:Previous studies identified circulating CD14+ HLA-DRlo/- monocytic cells as an immune suppressive subset in solid malignancies, such as prostate, renal cell carcinoma, and pancreatic cancer. Such monocytic cells have been implicated not only in tumour progression but also as a potential barrier for immunotherapy. This study examined the relationship between ... Read more >>

Am J Reprod Immunol (American journal of reproductive immunology (New York, N.Y. : 1989))
[2020, :e13343]

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Granulocytic Myeloid-Derived Suppressor Cells as Negative Regulators of Anticancer Immunity.

Elliot D Kramer, Scott I Abrams,

The immune system plays a critical role in cancer progression and response to therapy. However, the immune system can be compromised during the neoplastic process. Notably, the myeloid lineage, which gives rise to granulocytic cells, including neutrophils, is a well-recognized target of tumor-mediated immune suppression. Ordinarily, granulocytic cells are integral ... Read more >>

Front Immunol (Frontiers in immunology)
[2020, 11:1963]

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Targeting dual signalling pathways in concert with immune checkpoints for the treatment of pancreatic cancer.

Erik S Knudsen, Vishnu Kumarasamy, Sejin Chung, Amanda Ruiz, Paris Vail, Stephanie Tzetzo, Jin Wu, Ram Nambiar, Jared Sivinski, Shailender S Chauhan, Mukund Seshadri, Scott I Abrams, Jianmin Wang, Agnieszka K Witkiewicz,

OBJECTIVE:This study exploits the intersection between molecular-targeted therapies and immune-checkpoint inhibition to define new means to treat pancreatic cancer. DESIGN:Patient-derived cell lines and xenograft models were used to define the response to CDK4/6 and MEK inhibition in the tumour compartment. Impacts relative to immunotherapy were performed using subcutaneous and orthotopic ... Read more >>

Gut (Gut)
[2020, :]

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Blockade of p38 kinase impedes the mobilization of protumorigenic myeloid populations to impact breast cancer metastasis.

Justin Zonneville, Sean Colligan, Sydney Grant, Alexandra Miller, Paul Wallace, Scott I Abrams, Andrei V Bakin,

Patients with metastatic breast cancer (MBC) have limited therapeutic options and novel treatments are critically needed. Prior research implicates tumor-induced mobilization of myeloid cell populations in metastatic progression, as well as being an unfavorable outcome in MBC; however, the underlying mechanisms for these relationships remain unknown. Here, we provide evidence ... Read more >>

Int J Cancer (International journal of cancer)
[2020, 147(8):2279-2292]

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Platelet glycoprotein VI promotes metastasis through interaction with cancer cell-derived galectin-3.

Elmina Mammadova-Bach, Jesus Gil-Pulido, Edita Sarukhanyan, Philipp Burkard, Sergey Shityakov, Charlotte Schonhart, David Stegner, Katharina Remer, Paquita Nurden, Alan T Nurden, Thomas Dandekar, Laszlo Nehez, Magdolna Dank, Attila Braun, Diego Mezzano, Scott I Abrams, Bernhard Nieswandt,

Increasing evidence suggests that platelets play a predominant role in colon and breast cancer metastasis, but the underlying molecular mechanisms remain elusive. Glycoprotein VI (GPVI) is a platelet-specific receptor for collagen and fibrin that triggers platelet activation through immunoreceptor tyrosine-based activation motif (ITAM) signaling and thereby regulates diverse functions, including ... Read more >>

Blood (Blood)
[2020, 135(14):1146-1160]

Cited: 1 time

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Quantification of Early-Stage Myeloid-Derived Suppressor Cells in Cancer Requires Excluding Basophils.

Anm Nazmul H Khan, Tiffany R Emmons, Jerry T Wong, Emad Alqassim, Kelly L Singel, Jaron Mark, Brandon E Smith, Joseph D Tario, Kevin H Eng, Kirsten B Moysich, Kunle Odunsi, Scott I Abrams, Brahm H Segal,

Myeloid derived suppressor cells (MDSC) are a heterogeneous group of immature cells that accumulate in the peripheral blood and tumor microenvironment and are barriers to cancer therapy. MDSCs serve as prognostic biomarkers and are targets for therapy. On the basis of surface markers, three subsets of MDSCs have been defined ... Read more >>

Cancer Immunol Res (Cancer immunology research)
[2020, 8(6):819-828]

Cited: 1 time

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Inhibition of LSD1 in MDS progenitors restores differentiation of CD141Hi conventional dendritic cells.

Pragya Srivastava, Stephanie L Tzetzo, Eduardo Cortes Gomez, Kevin H Eng, Sheila N Jani Sait, Joseph B Kuechle, Prashant K Singh, Kitty De Jong, Kyle R Wiatrowski, Jennifer Peresie, Ava Dimitroff, Miranda L Lynch, Jianmin Wang, Scott I Abrams, Elizabeth A Griffiths, Michael J Nemeth,

The use of immunotherapy to treat patients with myelodysplastic syndromes (MDS) shows promise but is limited by our incomplete understanding of the immunologic milieu. In solid tumors, CD141Hi conventional dendritic cells (CD141Hi cDCs) are necessary for antitumor immunosurveillance and the response to immunotherapy. Here, we found that CD141Hi cDCs are ... Read more >>

Leukemia (Leukemia)
[2020, 34(9):2460-2472]

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Myeloid-driven mechanisms as barriers to antitumor CD8+ T cell activity.

Sean H Colligan, Stephanie L Tzetzo, Scott I Abrams,

The adaptive immune system is essential for host defense against pathogenic challenges, and a major constituent is the CD8+ cytotoxic T cell. Ordinarily, CD8+ T cells are endowed with a unique ability to specifically recognize and destroy their targets. However, in cases where disease emerges, especially in cancer, the efficacy ... Read more >>

Mol Immunol (Molecular immunology)
[2020, 118:165-173]

Cited: 1 time

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β2 adrenergic receptor-mediated signaling regulates the immunosuppressive potential of myeloid-derived suppressor cells.

Hemn Mohammadpour, Cameron R MacDonald, Guanxi Qiao, Minhui Chen, Bowen Dong, Bonnie L Hylander, Philip L McCarthy, Scott I Abrams, Elizabeth A Repasky,

Catecholamines released by sympathetic nerves can activate adrenergic receptors present on nearly every cell type, including myeloid-derived suppressor cells (MDSCs). Using in vitro systems, murine tumor models in wild-type and genetically modified (β2-AR-/-) mice, and adoptive transfer approaches, we found that the degree of β2-AR signaling significantly influences MDSC frequency ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2019, 129(12):5537-5552]

Cited: 7 times

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A Call for Epidemiological Research on Myeloid-Derived Suppressor Cells in Ovarian Cancer: A Review of the Existing Immunological Evidence and Suggestions for Moving Forward.

Ashley E Stenzel, Scott I Abrams, Kirsten B Moysich,

Recently, there have been encouraging findings suggesting that myeloid-derived suppressor cells (MDSCs) may be a good target for studying immune suppression in ovarian cancer. MDSCs are an abundance of immature myeloid cells that have demonstrated the ability to decrease tumor-infiltrating immune cells, increase the accrual of tumor-associated macrophages and regulatory ... Read more >>

Front Immunol (Frontiers in immunology)
[2019, 10:1608]

Cited: 2 times

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Identification of monocyte-like precursors of granulocytes in cancer as a mechanism for accumulation of PMN-MDSCs.

Jérôme Mastio, Thomas Condamine, George Dominguez, Andrew V Kossenkov, Laxminarasimha Donthireddy, Filippo Veglia, Cindy Lin, Fang Wang, Shuyu Fu, Jie Zhou, Patrick Viatour, Sergio Lavilla-Alonso, Alexander T Polo, Evgenii N Tcyganov, Charles Mulligan, Brian Nam, Joseph Bennett, Gregory Masters, Michael Guarino, Amit Kumar, Yulia Nefedova, Robert H Vonderheide, Lucia R Languino, Scott I Abrams, Dmitry I Gabrilovich,

We have identified a precursor that differentiates into granulocytes in vitro and in vivo yet belongs to the monocytic lineage. We have termed these cells monocyte-like precursors of granulocytes (MLPGs). Under steady state conditions, MLPGs were absent in the spleen and barely detectable in the bone marrow (BM). In contrast, ... Read more >>

J Exp Med (The Journal of experimental medicine)
[2019, 216(9):2150-2169]

Cited: 4 times

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Tumor-associated macrophage expression of interferon regulatory Factor-8 (IRF8) is a predictor of progression and patient survival in renal cell carcinoma.

Jason B Muhitch, Nicholas C Hoffend, Gissou Azabdaftari, Austin Miller, Wiam Bshara, Carl D Morrison, Thomas Schwaab, Scott I Abrams,

Tumor-associated macrophages have been well-characterized in solid malignancies, including renal cell carcinoma and generally correlate with poor prognosis. However, the molecular mechanisms which govern intratumoral macrophage behavior and patient outcome are unclear. Here, we investigated whether alterations in macrophage expression of the transcriptional regulator for myeloid commitment and function, interferon ... Read more >>

J Immunother Cancer (Journal for immunotherapy of cancer)
[2019, 7(1):155]

Cited: 3 times

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Inhibition of platelet GPVI induces intratumor hemorrhage and increases efficacy of chemotherapy in mice.

Julia Volz, Elmina Mammadova-Bach, Jesus Gil-Pulido, Rajender Nandigama, Katharina Remer, Lydia Sorokin, Alma Zernecke, Scott I Abrams, Süleyman Ergün, Erik Henke, Bernhard Nieswandt,

Maintenance of tumor vasculature integrity is indispensable for tumor growth and thus affects tumor progression. Previous studies have identified platelets as major regulators of tumor vascular integrity, as their depletion selectively rendered tumor vessels highly permeable and caused massive intratumoral hemorrhage. While these results established platelets as potential targets for ... Read more >>

Blood (Blood)
[2019, 133(25):2696-2706]

Cited: 3 times

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IFN regulatory factor-8 expression in macrophages governs an antimetastatic program.

Danielle Yf Twum, Sean H Colligan, Nicholas C Hoffend, Eriko Katsuta, Eduardo Cortes Gomez, Mary Lynn Hensen, Mukund Seshadri, Michael J Nemeth, Scott I Abrams,

High macrophage infiltration in cancer is associated with reduced survival in animal models and in patients. This reflects a shift in the macrophage response from a tumor-suppressive to tumor-supportive program governed by transcriptional events regulated by the inflammatory milieu. Although several transcription factors are known to drive a prometastatic program, ... Read more >>

JCI Insight (JCI insight)
[2019, 4(3):]

Cited: 3 times

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Loss of amphiregulin reduces myoepithelial cell coverage of mammary ducts and alters breast tumor growth.

Serena P H Mao, Minji Park, Ramon M Cabrera, John R Christin, George S Karagiannis, Maja H Oktay, Dietmar M W Zaiss, Scott I Abrams, Wenjun Guo, John S Condeelis, Paraic A Kenny, Jeffrey E Segall,

BACKGROUND:Amphiregulin (AREG), a ligand of the epidermal growth factor receptor, is not only essential for proper mammary ductal development, but also associated with breast cancer proliferation and growth. In the absence of AREG, mammary ductal growth is stunted and fails to expand. Furthermore, suppression of AREG expression in estrogen receptor-positive ... Read more >>

Breast Cancer Res (Breast cancer research : BCR)
[2018, 20(1):131]

Cited: 1 time

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An osteopontin/CD44 immune checkpoint controls CD8+ T cell activation and tumor immune evasion.

John D Klement, Amy V Paschall, Priscilla S Redd, Mohammed L Ibrahim, Chunwan Lu, Dafeng Yang, Esteban Celis, Scott I Abrams, Keiko Ozato, Kebin Liu,

Despite breakthroughs in immune checkpoint inhibitor (ICI) immunotherapy, not all human cancers respond to ICI immunotherapy and a large fraction of patients with the responsive types of cancers do not respond to current ICI immunotherapy. This clinical conundrum suggests that additional immune checkpoints exist. We report here that interferon regulatory ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2018, 128(12):5549-5560]

Cited: 8 times

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Dietary Protein Restriction Reprograms Tumor-Associated Macrophages and Enhances Immunotherapy.

Ashley Orillion, Nur P Damayanti, Li Shen, Remi Adelaiye-Ogala, Hayley Affronti, May Elbanna, Sreenivasulu Chintala, Michael Ciesielski, Luigi Fontana, Chinghai Kao, Bennett D Elzey, Timothy L Ratliff, David E Nelson, Dominic Smiraglia, Scott I Abrams, Roberto Pili,

PURPOSE:Diet and healthy weight are established means of reducing cancer incidence and mortality. However, the impact of diet modifications on the tumor microenvironment and antitumor immunity is not well defined. Immunosuppressive tumor-associated macrophages (TAMs) are associated with poor clinical outcomes and are potentially modifiable through dietary interventions. We tested the ... Read more >>

Clin Cancer Res (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2018, 24(24):6383-6395]

Cited: 5 times

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Case Study in International Cooperation: Cuba's Molecular Immunology Center and Roswell Park Cancer Institute.

Rachel Evans, Mary Reid, Brahm Segal, Scott I Abrams, Kelvin Lee,

In 1961, the USA severed diplomatic relations with Cuba, and in 1962 an embargo was imposed on trade and financial relations with that country. It was not until five decades later that the USA and Cuba would reestablish relations. This opened the way for the New York State Trade Mission ... Read more >>

MEDICC Rev (MEDICC review)
[2018, 20(2):35-39]

Cited: 1 time

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Genetic Variants in Immune-Related Pathways and Breast Cancer Risk in African American Women in the AMBER Consortium.

Chi-Chen Hong, Lara E Sucheston-Campbell, Song Liu, Qiang Hu, Song Yao, Kathryn L Lunetta, Stephen A Haddad, Edward A Ruiz-Narváez, Jeannette T Bensen, Ting-Yuan David Cheng, Elisa V Bandera, Lynn A Rosenberg, Christopher A Haiman, Kelvin Lee, Sharon S Evans, Scott I Abrams, Elizabeth A Repasky, Andrew F Olshan, Julie R Palmer, Christine B Ambrosone,

Background: Constitutional immunity shaped by exposure to endemic infectious diseases and parasitic worms in Sub-Saharan Africa may play a role in the etiology of breast cancer among African American (AA) women.Methods: A total of 149,514 gene variants in 433 genes across 45 immune pathways were analyzed in the AMBER consortium ... Read more >>

Cancer Epidemiol Biomarkers Prev (Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology)
[2018, 27(3):321-330]

Cited: 4 times

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Tumor-derived thymic stromal lymphopoietin enhances lung metastasis through an alveolar macrophage-dependent mechanism.

Lauren Burkard-Mandel, Rachel O'Neill, Sean Colligan, Mukund Seshadri, Scott I Abrams,

It is well-recognized that macrophages, which arise from circulating precursors, enhance tumor progression in patients and animal models. However, less is known regarding the role of tissue-resident macrophages in metastasis. Moreover, the identification of tumor factors which influence macrophage function in the metastatic niche remains incomplete. Here, we investigated one ... Read more >>

Oncoimmunology (Oncoimmunology)
[2018, 7(5):e1419115]

Cited: 3 times

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β-Adrenergic Signaling in Mice Housed at Standard Temperatures Suppresses an Effector Phenotype in CD8+ T Cells and Undermines Checkpoint Inhibitor Therapy.

Mark J Bucsek, Guanxi Qiao, Cameron R MacDonald, Thejaswini Giridharan, Lauren Evans, Brian Niedzwecki, Haichao Liu, Kathleen M Kokolus, Jason W-L Eng, Michelle N Messmer, Kristopher Attwood, Scott I Abrams, Bonnie L Hylander, Elizabeth A Repasky,

The immune context of tumors has significant prognostic value and is predictive of responsiveness to several forms of therapy, including immunotherapy. We report here that CD8+ T-cell frequency and functional orientation within the tumor microenvironment is regulated by β2-adrenergic receptor (β-AR) signaling in host immune cells. We used three strategies-physiologic ... Read more >>

Cancer Res (Cancer research)
[2017, 77(20):5639-5651]

Cited: 23 times

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Cancer in primary immunodeficiency diseases: Cancer incidence in the United States Immune Deficiency Network Registry.

Paul C Mayor, Kevin H Eng, Kelly L Singel, Scott I Abrams, Kunle Odunsi, Kirsten B Moysich, Ramsay Fuleihan, Elizabeth Garabedian, Patricia Lugar, Hans D Ochs, Francisco A Bonilla, Rebecca H Buckley, Kathleen E Sullivan, Zuhair K Ballas, Charlotte Cunningham-Rundles, Brahm H Segal,

BACKGROUND:We evaluated the overall and site-specific incidence of cancer in subjects with primary immunodeficiency diseases (PIDD) enrolled in the United States Immune Deficiency Network (USIDNET) registry compared with age-adjusted cancer incidence in the Surveillance, Epidemiology and End Results Program (SEER) database. OBJECTIVE:We hypothesized that subjects with PIDD would have an ... Read more >>

J Allergy Clin Immunol (The Journal of allergy and clinical immunology)
[2018, 141(3):1028-1035]

Cited: 31 times

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Editorial: The rebirth of myeloid-derived suppressor cells: from adversary in cancer to ally in reproductive health.

Scott I Abrams,

J Leukoc Biol (Journal of leukocyte biology)
[2017, 101(5):1079]

Cited: 0 times

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