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Article ; Online: Exosomal PD-L1: Roles in Tumor Progression and Immunotherapy.

Morrissey, Samantha M / Yan, Jun

2020 Volume 6, Issue 7, Page(s) 550–558

Abstract: The use of immune checkpoint therapies targeting programmed death-1 (PD-1) and its ligand (PD-L1) continue to show limited durable success in clinical cases despite widespread application. While some patients achieve complete responses and disease ... ...

Abstract	The use of immune checkpoint therapies targeting programmed death-1 (PD-1) and its ligand (PD-L1) continue to show limited durable success in clinical cases despite widespread application. While some patients achieve complete responses and disease remission, others are completely resistant to the therapy. Recent evidence in the field suggests that tumor-derived exosomes could be responsible for mediating systemic immunosuppression that antagonizes anti-PD-1 checkpoint therapy. In this Opinion article, we discuss our claim that endogenous tumor exosomal PD-L1 and tumor-derived exosome-induced PD-L1 are two of the most notable mechanisms of exosome-mediated resistance against antitumor immunity and we discuss how this resistance could directly influence immune checkpoint therapy failure.
MeSH term(s)	Animals ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; B7-H1 Antigen/antagonists & inhibitors ; B7-H1 Antigen/immunology ; B7-H1 Antigen/metabolism ; Disease Progression ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/immunology ; Exosomes/drug effects ; Exosomes/immunology ; Exosomes/metabolism ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Immune Checkpoint Inhibitors/therapeutic use ; Macrophages/immunology ; Macrophages/metabolism ; Mice ; Neoplasms/drug therapy ; Neoplasms/immunology ; T-Lymphocytes, Cytotoxic/immunology ; Treatment Failure ; Tumor Burden/drug effects ; Tumor Burden/immunology ; Tumor Escape/drug effects ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/immunology ; Xenograft Model Antitumor Assays
Chemical Substances	B7-H1 Antigen ; CD274 protein, human ; Cd274 protein, mouse ; Immune Checkpoint Inhibitors
Language	English
Publishing date	2020-03-29
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2852626-0
ISSN	2405-8025 ; 2405-8033 ; 2405-8033
ISSN (online)	2405-8025 ; 2405-8033
ISSN	2405-8033
DOI	10.1016/j.trecan.2020.03.002
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Article ; Online: Distinct Growth Responses of Tundra Soil Bacteria to Short-Term and Long-Term Warming.

Propster, Jeffrey R / Schwartz, Egbert / Hayer, Michaela / Miller, Samantha / Monsaint-Queeney, Victoria / Koch, Benjamin J / Morrissey, Ember M / Mack, Michelle C / Hungate, Bruce A

Applied and environmental microbiology

2023 Volume 89, Issue 3, Page(s) e0154322

Abstract: Increases in Arctic temperatures have thawed permafrost and accelerated tundra soil microbial activity, releasing greenhouse gases that amplify climate warming. Warming over time has also accelerated shrub encroachment in the tundra, altering plant input ...

Abstract	Increases in Arctic temperatures have thawed permafrost and accelerated tundra soil microbial activity, releasing greenhouse gases that amplify climate warming. Warming over time has also accelerated shrub encroachment in the tundra, altering plant input abundance and quality, and causing further changes to soil microbial processes. To better understand the effects of increased temperature and the accumulated effects of climate change on soil bacterial activity, we quantified the growth responses of individual bacterial taxa to short-term warming (3 months) and long-term warming (29 years) in moist acidic tussock tundra. Intact soil was assayed in the field for 30 days using
MeSH term(s)	Soil ; Ecosystem ; Phylogeny ; Tundra ; Arctic Regions ; Climate Change ; Carbon/metabolism
Chemical Substances	Soil ; Carbon (7440-44-0)
Language	English
Publishing date	2023-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	223011-2
ISSN	1098-5336 ; 0099-2240
ISSN (online)	1098-5336
ISSN	0099-2240
DOI	10.1128/aem.01543-22
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Article ; Online: Investigation of the Frequency of Detection of Common Respiratory Pathogens in Nasal Secretions and Environment of Healthy Sport Horses Attending a Multi-Week Show Event during the Summer Months.

Pusterla, Nicola / Kalscheur, Madalyn / Peters, Duncan / Bidwell, Lori / Holtz, Sara / Barnum, Samantha / Lawton, Kaila / Morrissey, Matt / Schumacher, Stephen

Viruses

2023 Volume 15, Issue 6

Abstract: Little information is presently available regarding the frequency of the silent shedders of respiratory viruses in healthy sport horses and their impact on environmental contamination. Therefore, the aim of this study was to investigate the detection ... ...

Abstract	Little information is presently available regarding the frequency of the silent shedders of respiratory viruses in healthy sport horses and their impact on environmental contamination. Therefore, the aim of this study was to investigate the detection frequency of selected respiratory pathogens in nasal secretions and environmental stall samples of sport horses attending a multi-week equestrian event during the summer months. Six out of fifteen tents were randomly selected for the study with approximately 20 horse/stall pairs being sampled on a weekly basis. Following weekly collection for a total of 11 weeks, all samples were tested for the presence of common respiratory pathogens (EIV, EHV-1, EHV-4, ERAV, ERBV, and
MeSH term(s)	Horses ; Animals ; Horse Diseases ; Viruses ; Herpesvirus 1, Equid ; Seasons ; Herpesviridae Infections
Language	English
Publishing date	2023-05-24
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15061225
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Article ; Online: Sleep Duration Correlates With Performance in Ultra-Endurance Triathlon.

Kisiolek, Jacob N / Smith, Kyle A / Baur, Daniel A / Willingham, Brandon D / Morrissey, Margaret C / Leyh, Samantha M / Saracino, Patrick G / Mah, Cheri D / Ormsbee, Michael J

International journal of sports physiology and performance

2021 Volume 17, Issue 2, Page(s) 226–233

Abstract: The relationship between sleep duration, sleep quality, and race completion time during each stage of a 3-day ultra-endurance triathlon (stage 1: 10-km swim, 146-km cycle; stage 2: 276-km cycle; and stage 3: 84.4-km run) was investigated. Seventeen ... ...

Abstract	The relationship between sleep duration, sleep quality, and race completion time during each stage of a 3-day ultra-endurance triathlon (stage 1: 10-km swim, 146-km cycle; stage 2: 276-km cycle; and stage 3: 84.4-km run) was investigated. Seventeen triathletes partook in sleep analysis throughout the ultra-endurance multiday triathlon using an actigraphy wristband. The participants wore the band to record objective sleep outcomes for approximately 4 days (1-2 d prerace, 3 race days, and 1 d postrace), except while racing. The total sleep time (TST; prerace: 414.1 [95.3] min, prestage 1: 392.2 [138.3] min, prestage 2: 355.6 [62.5] min, and prestage 3: 299.7 [107.0] min) significantly decreased over time (P < .05). Significant Pearson moment-product correlations were found between TST and subsequent race-day performance for race stage 1 (r = -.577; P = .019) and stage 3 (r = -.546; P = .035), with further analysis revealing that TST explained 33% and 30% of the variation in performance for stages 1 and 3, respectively. During a 3-day ultra-endurance triathlon, the TST was reduced and had a significant negative correlation to exercise performance, indicating that sleep loss was associated with slower performances. Sleep onset latency, wake episodes, and sleep efficiency did not significantly change over the course of this investigation, which may stem from the close proximity of exercise to sleep.
MeSH term(s)	Bicycling ; Humans ; Physical Endurance ; Running ; Sleep ; Swimming
Language	English
Publishing date	2021-10-09
Publishing country	United States
Document type	Journal Article
ISSN	1555-0273
ISSN (online)	1555-0273
DOI	10.1123/ijspp.2021-0111
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Article ; Online: Changes in Hydration Factors Over the Course of Heat Acclimation in Endurance Athletes.

Sekiguchi, Yasuki / Benjamin, Courteney L / Dion, Samantha O / Manning, Ciara N / Struder, Jeb F / Dierickx, Erin E / Morrissey, Margaret C / Filep, Erica M / Casa, Douglas J

International journal of sport nutrition and exercise metabolism

2021 Volume 31, Issue 5, Page(s) 406–411

Abstract: The purpose of this study was to examine the effect of heat acclimation (HA) on thirst levels, sweat rate, and percentage of body mass loss (%BML), and changes in fluid intake factors throughout HA induction. Twenty-eight male endurance athletes (mean ± ... ...

Abstract	The purpose of this study was to examine the effect of heat acclimation (HA) on thirst levels, sweat rate, and percentage of body mass loss (%BML), and changes in fluid intake factors throughout HA induction. Twenty-eight male endurance athletes (mean ± SD; age, 35 ± 12 years; body mass, 73.0 ± 8.9 kg; maximal oxygen consumption, 57.4 ± 6.8 ml·kg-1·min-1) completed 60 min of exercise in a euhydrated state at 58.9 ± 2.3% velocity of maximal oxygen consumption in the heat (ambient temperature, 35.0 ± 1.3 °C; relative humidity, 48.0 ± 1.3%) prior to and following HA where thirst levels, sweat rate, and %BML were measured. Then, participants performed 5 days of HA while held at hyperthermia (38.50-39.75 °C) for 60 min with fluid provided ad libitum. Sweat volume, %BML, thirst levels, and fluid intake were measured for each session. Thirst levels were significantly lower following HA (pre, 4 ± 1; post, 3 ± 1, p < .001). Sweat rate (pre, 1.76 ± 0.42 L/hr; post, 2.00 ± 0.60 L/hr, p = .039) and %BML (pre, 2.66 ± 0.53%; post, 2.98 ± 0.83%, p = .049) were significantly greater following HA. During HA, thirst levels decreased (Day 1, 4 ± 1; Day 2, 3 ± 2; Day 3, 3 ± 2; Day 4, 3 ± 1; Day 5, 3 ± 1; p < .001). However, sweat volume (Day 1, 2.34 ± 0.67 L; Day 2, 2.49 ± 0.58 L; Day 3, 2.67 ± 0.63 L; Day 4, 2.74 ± 0.61 L; Day 5, 2.74 ± 0.91 L; p = .010) and fluid intake (Day 1, 1.20 ± 0.45 L; Day 2, 1.52 ± 0.58 L; Day 3, 1.69 ± 0.63 L; Day 4, 1.65 ± 0.58 L; Day 5, 1.74 ± 0.51 L; p < .001) increased. In conclusion, thirst levels were lower following HA even though sweat rate and %BML were higher. Thirst levels decreased while sweat volume and fluid intake increased during HA induction. Thus, HA should be one of the factors to consider when planning hydration strategies.
MeSH term(s)	Acclimatization ; Adult ; Athletes ; Drinking ; Hot Temperature ; Humans ; Male ; Middle Aged ; Sweating ; Thirst ; Young Adult
Language	English
Publishing date	2021-07-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	1101115-4
ISSN	1543-2742 ; 1050-1606 ; 1526-484X
ISSN (online)	1543-2742
ISSN	1050-1606 ; 1526-484X
DOI	10.1123/ijsnem.2020-0374
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Article ; Online: The temperature sensitivity of soil: microbial biodiversity, growth, and carbon mineralization.

Wang, Chao / Morrissey, Ember M / Mau, Rebecca L / Hayer, Michaela / Piñeiro, Juan / Mack, Michelle C / Marks, Jane C / Bell, Sheryl L / Miller, Samantha N / Schwartz, Egbert / Dijkstra, Paul / Koch, Benjamin J / Stone, Bram W / Purcell, Alicia M / Blazewicz, Steven J / Hofmockel, Kirsten S / Pett-Ridge, Jennifer / Hungate, Bruce A

The ISME journal

2021 Volume 15, Issue 9, Page(s) 2738–2747

Abstract: Microorganisms drive soil carbon mineralization and changes in their activity with increased temperature could feedback to climate change. Variation in microbial biodiversity and the temperature sensitivities ( ... ...

Abstract	Microorganisms drive soil carbon mineralization and changes in their activity with increased temperature could feedback to climate change. Variation in microbial biodiversity and the temperature sensitivities (Q
MeSH term(s)	Biodiversity ; Carbon ; Ecosystem ; Phylogeny ; Soil ; Soil Microbiology ; Temperature
Chemical Substances	Soil ; Carbon (7440-44-0)
Language	English
Publishing date	2021-03-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2406536-5
ISSN	1751-7370 ; 1751-7362
ISSN (online)	1751-7370
ISSN	1751-7362
DOI	10.1038/s41396-021-00959-1
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Article ; Online: Tumor-derived exosomes drive immunosuppressive macrophages in a pre-metastatic niche through glycolytic dominant metabolic reprogramming.

Morrissey, Samantha M / Zhang, Fan / Ding, Chuanlin / Montoya-Durango, Diego Elias / Hu, Xiaoling / Yang, Chenghui / Wang, Zhen / Yuan, Fang / Fox, Matthew / Zhang, Huang-Ge / Guo, Haixun / Tieri, David / Kong, Maiying / Watson, Corey T / Mitchell, Robert A / Zhang, Xiang / McMasters, Kelly M / Huang, Jian / Yan, Jun

Cell metabolism

2021 Volume 33, Issue 10, Page(s) 2040–2058.e10

Abstract: One of the defining characteristics of a pre-metastatic niche, a fundamental requirement for primary tumor metastasis, is infiltration of immunosuppressive macrophages. How these macrophages acquire their phenotype remains largely unexplored. Here, we ... ...

Abstract	One of the defining characteristics of a pre-metastatic niche, a fundamental requirement for primary tumor metastasis, is infiltration of immunosuppressive macrophages. How these macrophages acquire their phenotype remains largely unexplored. Here, we demonstrate that tumor-derived exosomes (TDEs) polarize macrophages toward an immunosuppressive phenotype characterized by increased PD-L1 expression through NF-kB-dependent, glycolytic-dominant metabolic reprogramming. TDE signaling through TLR2 and NF-κB leads to increased glucose uptake. TDEs also stimulate elevated NOS2, which inhibits mitochondrial oxidative phosphorylation resulting in increased conversion of pyruvate to lactate. Lactate feeds back on NF-κB, further increasing PD-L1. Analysis of metastasis-negative lymph nodes of non-small-cell lung cancer patients revealed that macrophage PD-L1 positively correlates with levels of GLUT-1 and vesicle release gene YKT6 from primary tumors. Collectively, our study provides a novel mechanism by which macrophages within a pre-metastatic niche acquire their immunosuppressive phenotype and identifies an important link among exosomes, metabolism, and metastasis.
MeSH term(s)	Carcinoma, Non-Small-Cell Lung/metabolism ; Cell Line, Tumor ; Exosomes/metabolism ; Glycolysis ; Humans ; Lung Neoplasms/metabolism ; Macrophages/metabolism ; R-SNARE Proteins/metabolism ; Tumor Microenvironment
Chemical Substances	R-SNARE Proteins ; YKT6 protein, human
Language	English
Publishing date	2021-09-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2176834-1
ISSN	1932-7420 ; 1550-4131
ISSN (online)	1932-7420
ISSN	1550-4131
DOI	10.1016/j.cmet.2021.09.002
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Article ; Online: Lactate supports a metabolic-epigenetic link in macrophage polarization.

Science advances

2021 Volume 7, Issue 46, Page(s) eabi8602

Abstract: Lactate accumulation is a hallmark of solid cancers and is linked to the immune suppressive phenotypes of tumor-infiltrating immune cells. We report herein that interleukin-4 (IL-4)–induced M0 → M2 macrophage polarization is accompanied by ... ...

Abstract	Lactate accumulation is a hallmark of solid cancers and is linked to the immune suppressive phenotypes of tumor-infiltrating immune cells. We report herein that interleukin-4 (IL-4)–induced M0 → M2 macrophage polarization is accompanied by interchangeable glucose- or lactate-dependent tricarboxylic acid (TCA) cycle metabolism that directly drives histone acetylation, M2 gene transcription, and functional immune suppression. Lactate-dependent M0 → M2 polarization requires both mitochondrial pyruvate uptake and adenosine triphosphate–citrate lyase (ACLY) enzymatic activity. Notably, exogenous acetate rescues defective M2 polarization and histone acetylation following mitochondrial pyruvate carrier 1 (MPC1) inhibition or ACLY deficiency. Lastly, M2 macrophage–dependent tumor progression is impaired by conditional macrophage ACLY deficiency, further supporting a dominant role for glucose/lactate mitochondrial metabolism and histone acetylation in driving immune evasion. This work adds to our understanding of how mitochondrial metabolism affects macrophage functional phenotypes and identifies a unique tumor microenvironment (TME)–driven metabolic-epigenetic link in M2 macrophages.
Language	English
Publishing date	2021-11-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abi8602
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Article ; Online: Ultra-endurance triathlon performance and markers of whole-body and gut-specific inflammation.

Smith, Kyle A / Kisiolek, Jacob N / Willingham, Brandon D / Morrissey, Margaret C / Leyh, Samantha M / Saracino, Patrick G / Baur, Daniel A / Cook, Marc D / Ormsbee, Michael J

European journal of applied physiology

2019 Volume 120, Issue 2, Page(s) 349–357

Abstract: Purpose: To examine the influence of the Ultraman Florida triathlon (3 days of non-continuous racing; stage 1: 10 km swim and 144.8 km cycle; stage 2: 275.4 km cycle; stage 3: 84.4 km run) on circulating plasma concentrations of whole-body (C-reactive ... ...

Abstract	Purpose: To examine the influence of the Ultraman Florida triathlon (3 days of non-continuous racing; stage 1: 10 km swim and 144.8 km cycle; stage 2: 275.4 km cycle; stage 3: 84.4 km run) on circulating plasma concentrations of whole-body (C-reactive protein (CRP), interleukin (IL)-6 (IL-6), and IL-10 and surrogate gut-specific inflammatory markers (IL-17 and IL-23), and determine whether these variables are associated with performance. Methods: Eighteen triathletes (N = 18; 15 men, 3 women; age: 37 ± 8 yrs) were evaluated at baseline and post-race for circulating concentrations of CRP, IL-6, IL-10, IL-17, and IL-23. Blood samples were drawn two days prior to stage 1 (1600 h) and one day after stage 3 (1200 h). Results: Plasma CRP significantly increased from baseline (1985.8 ± 5962.3 ng/mL) to post-race (27,013.9 ± 12,888.8 ng/mL, p < 0.001, 13-fold increase). Both plasma IL-6 and IL-10 did not significantly change from baseline to post-race. Baseline and post-race concentrations of IL-17 and IL-23 were below detectable limits. Pearson's correlation between mean finish time and post-race IL-10 revealed a significant positive correlation (r = 0.54, p < 0.05). Conclusions: Our results suggest that cytokines such as IL-6 and IL-10 involved in the inflammatory response return to near-baseline concentrations rapidly even after ultra-endurance events of extreme duration. The absence of IL-17 and IL-23 may suggest positive gut adaptations from ultra-endurance training. A significant positive correlation between post-race IL-10 concentrations and mean finish time may indicate that a relationship between anti-inflammatory responses and performance exists.
MeSH term(s)	Adult ; Bicycling/physiology ; Biomarkers/blood ; Cytokines/blood ; Female ; Gastrointestinal Tract/metabolism ; Humans ; Inflammation/blood ; Inflammation/metabolism ; Male ; Middle Aged ; Physical Endurance ; Running/physiology ; Sports ; Swimming/physiology
Chemical Substances	Biomarkers ; Cytokines
Language	English
Publishing date	2019-12-11
Publishing country	Germany
Document type	Journal Article
ZDB-ID	124793-1
ISSN	1439-6327 ; 1432-1025 ; 0301-5548 ; 1439-6319
ISSN (online)	1439-6327 ; 1432-1025
ISSN	0301-5548 ; 1439-6319
DOI	10.1007/s00421-019-04279-3
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Article ; Online: The Functional Significance of Bacterial Predators.

Hungate, Bruce A / Marks, Jane C / Power, Mary E / Schwartz, Egbert / van Groenigen, Kees Jan / Blazewicz, Steven J / Chuckran, Peter / Dijkstra, Paul / Finley, Brianna K / Firestone, Mary K / Foley, Megan / Greenlon, Alex / Hayer, Michaela / Hofmockel, Kirsten S / Koch, Benjamin J / Mack, Michelle C / Mau, Rebecca L / Miller, Samantha N / Morrissey, Ember M /

Propster, Jeffrey R / Purcell, Alicia M / Sieradzki, Ella / Starr, Evan P / Stone, Bram W G / Terrer, César / Pett-Ridge, Jennifer

mBio

2021 Volume 12, Issue 2

Abstract: Predation structures food webs, influences energy flow, and alters rates and pathways of nutrient cycling through ecosystems, effects that are well documented for macroscopic predators. In the microbial world, predatory bacteria are common, yet little is ...

Abstract	Predation structures food webs, influences energy flow, and alters rates and pathways of nutrient cycling through ecosystems, effects that are well documented for macroscopic predators. In the microbial world, predatory bacteria are common, yet little is known about their rates of growth and roles in energy flows through microbial food webs, in part because these are difficult to quantify. Here, we show that growth and carbon uptake were higher in predatory bacteria compared to nonpredatory bacteria, a finding across 15 sites, synthesizing 82 experiments and over 100,000 taxon-specific measurements of element flow into newly synthesized bacterial DNA. Obligate predatory bacteria grew 36% faster and assimilated carbon at rates 211% higher than nonpredatory bacteria. These differences were less pronounced for facultative predators (6% higher growth rates, 17% higher carbon assimilation rates), though high growth and carbon assimilation rates were observed for some facultative predators, such as members of the genera
MeSH term(s)	Animals ; Bacteria/classification ; Bacteria/genetics ; Bacteria/growth & development ; Bacteria/metabolism ; Bacterial Physiological Phenomena ; Bacteriophages ; Carbon/metabolism ; DNA, Bacterial/genetics ; Deltaproteobacteria/genetics ; Deltaproteobacteria/physiology
Chemical Substances	DNA, Bacterial ; Carbon (7440-44-0)
Language	English
Publishing date	2021-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mBio.00466-21
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