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Article ; Online: Tumor hypermetabolism confers resistance to immunotherapy.

Liu, Arthur / Curran, Michael A

2020 Volume 65, Page(s) 155–163

Abstract: Advances in our understanding of tumor immune biology and development of cancer immunotherapies have led to improved outcomes for patients that suffer from aggressive cancers such as metastatic melanoma. Despite these advances, a significant proportion ... ...

Abstract	Advances in our understanding of tumor immune biology and development of cancer immunotherapies have led to improved outcomes for patients that suffer from aggressive cancers such as metastatic melanoma. Despite these advances, a significant proportion of patients still fail to benefit, and as a result, attention has shifted to understanding how cancer cells escape immune destruction. Of particular interest is the metabolic landscape of the tumor microenvironment, as recent studies have demonstrated how both competition for essential nutrients and depletion of specific amino acids can promote T cell dysfunction. Here, we will discuss the major energetic pathways engaged by both T cells and cancer cells, metabolic substrates present in the tumor microenvironment, and emerging therapeutic strategies that seek to improve T cell metabolic fitness and bolster the antitumor immune response.
MeSH term(s)	Drug Resistance, Neoplasm/immunology ; Humans ; Immunotherapy/adverse effects ; Melanoma/immunology ; Melanoma/therapy ; Mitochondrial Diseases ; Neoplasm Metastasis ; Neoplasms/immunology ; Neoplasms/therapy ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/immunology
Language	English
Publishing date	2020-01-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1033980-2
ISSN	1096-3650 ; 1044-579X
ISSN (online)	1096-3650
ISSN	1044-579X
DOI	10.1016/j.semcancer.2020.01.009
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Article ; Online: Hypoxia-activated prodrug and antiangiogenic therapies cooperatively treat pancreatic cancer but elicit immunosuppressive G-MDSC infiltration.

Liu, Arthur / Gammon, Seth T / Pisaneschi, Federica / Boda, Akash / Ager, Casey R / Piwnica-Worms, David / Hong, David S / Curran, Michael A

JCI insight

2024 Volume 9, Issue 1

Abstract: We previously showed that ablation of tumor hypoxia can sensitize tumors to immune checkpoint blockade (ICB). Here, we used a Kras+/G12D TP53+/R172H Pdx1-Cre-derived (KPC-derived) model of pancreatic adenocarcinoma to examine the tumor response and ... ...

Abstract	We previously showed that ablation of tumor hypoxia can sensitize tumors to immune checkpoint blockade (ICB). Here, we used a Kras+/G12D TP53+/R172H Pdx1-Cre-derived (KPC-derived) model of pancreatic adenocarcinoma to examine the tumor response and adaptive resistance mechanisms involved in response to 2 established methods of hypoxia-reducing therapy: the hypoxia-activated prodrug TH-302 and vascular endothelial growth factor receptor 2 (VEGFR-2) blockade. The combination of both modalities normalized tumor vasculature, increased DNA damage and cell death, and delayed tumor growth. In contrast with prior cancer models, the combination did not alleviate overall tissue hypoxia or sensitize these KPC tumors to ICB therapy despite qualitative improvements to the CD8+ T cell response. Bulk tumor RNA sequencing, flow cytometry, and adoptive myeloid cell transfer suggested that treated tumor cells increased their capacity to recruit granulocytic myeloid-derived suppressor cells (G-MDSCs) through CCL9 secretion. Blockade of the CCL9/CCR1 axis could limit G-MDSC migration, and depletion of Ly6G-positive cells could sensitize tumors to the combination of TH-302, anti-VEGFR-2, and ICB. Together, these data suggest that pancreatic tumors modulate G-MDSC migration as an adaptive response to vascular normalization and that these immunosuppressive myeloid cells act in a setting of persistent hypoxia to maintain adaptive immune resistance.
MeSH term(s)	Humans ; Pancreatic Neoplasms/pathology ; Myeloid-Derived Suppressor Cells ; Adenocarcinoma/pathology ; Vascular Endothelial Growth Factor A/metabolism ; Hypoxia/metabolism
Chemical Substances	TH 302 ; Vascular Endothelial Growth Factor A
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.169150
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Article ; Online: Reminders.

Liu, Arthur K

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2012 Volume 30, Issue 4, Page(s) 459–460

MeSH term(s)	Female ; Humans ; Male ; Physician-Patient Relations ; Reminder Systems
Language	English
Publishing date	2012-02-01
Publishing country	United States
Document type	Editorial
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.2011.39.9089
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Zs.A 1847: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Identification of Nonfunctional Alternatively Spliced Isoforms of STING in Human Acute Myeloid Leukemia.

Boda, Akash R / Liu, Arthur J / Castro-Pando, Susana / Whitfield, Benjamin T / Molldrem, Jeffrey J / Al-Atrash, Gheath / Di Francesco, Maria Emilia / Jones, Philip / Ager, Casey R / Curran, Michael A

Cancer research communications

2024 Volume 4, Issue 3, Page(s) 911–918

Abstract: Lack of robust activation of Stimulator of Interferon Genes (STING) pathway and subsequent induction of type I IFN responses is considered a barrier to antitumor immunity in acute myeloid leukemia (AML). Using common human AML cell lines as in vitro ... ...

Abstract	Lack of robust activation of Stimulator of Interferon Genes (STING) pathway and subsequent induction of type I IFN responses is considered a barrier to antitumor immunity in acute myeloid leukemia (AML). Using common human AML cell lines as in vitro tools to evaluate the efficacy of novel STING agonists, we found most AML lines to be poor producers of IFNs upon exposure to extremely potent agonists, suggesting cell-intrinsic suppression of STING signaling may occur. We observed unexpected patterns of response that did not correlate with levels of STING pathway components or of known enzymes associated with resistance. To identify a genetic basis for these observations, we cloned and sequenced STING from the cDNA of human AML cell lines and found both frequent mutations and deviations from normal RNA splicing. We identified two novel spliced isoforms of STING in these lines and validated their expression in primary human AML samples. When transduced into reporter cells, these novel STING isoforms exhibited complete insensitivity to agonist stimulation. These observations identify alternative splicing as a mechanism of STING pathway suppression and suggest that most AML silences the STING pathway through direct modification rather than through engagement of external inhibitory factors. Significance: We find that AML acquires resistance to innate immune activation via the STING pathway through aberrant splicing of the STING transcript including two novel forms described herein that act as dominant negatives. These data broaden understanding of how cancers evolve STING resistance, and suggest that the AML tumor microenvironment, not the cancer cell, should be the target of therapeutic interventions to activate STING.
MeSH term(s)	Humans ; Protein Isoforms/genetics ; Leukemia, Myeloid, Acute/genetics ; Alternative Splicing/genetics ; Interferon Type I/genetics ; Cell Line ; Tumor Microenvironment
Chemical Substances	Protein Isoforms ; Interferon Type I
Language	English
Publishing date	2024-03-13
Publishing country	United States
Document type	Journal Article
ISSN	2767-9764
ISSN (online)	2767-9764
DOI	10.1158/2767-9764.CRC-24-0095
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Article ; Online: Reply: The Optimal Dose of Hypofractionated Radiotherapy in Diffuse Intrinsic Pontine Glioma (DIPG).

Hankinson, Todd C / Liu, Arthur K

Pediatric blood & cancer

2016 Volume 63, Issue 5, Page(s) 949

MeSH term(s)	Brain Stem Neoplasms/radiotherapy ; Female ; Glioma/radiotherapy ; Humans ; Male ; Pons/pathology
Language	English
Publishing date	2016-05
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.25916
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Zs.A 1131: Show issues

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Article ; Online: Detectability of Small Low-Attenuation Lesions With Deep Learning CT Image Reconstruction: A 24-Reader Phantom Study.

Toia, Giuseppe V / Zamora, David A / Singleton, Michael / Liu, Arthur / Tan, Edward / Leng, Shuai / Shuman, William P / Kanal, Kalpana M / Mileto, Achille

AJR. American journal of roentgenology

2022 Volume 220, Issue 2, Page(s) 283–295

Abstract: BACKGROUND. ...

Abstract	BACKGROUND.
MeSH term(s)	Humans ; Deep Learning ; Radiation Dosage ; Radiographic Image Interpretation, Computer-Assisted/methods ; Tomography, X-Ray Computed/methods ; Algorithms ; Phantoms, Imaging ; Image Processing, Computer-Assisted
Language	English
Publishing date	2022-09-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	82076-3
ISSN	1546-3141 ; 0361-803X ; 0092-5381
ISSN (online)	1546-3141
ISSN	0361-803X ; 0092-5381
DOI	10.2214/AJR.22.28407
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Article: Genetic Predictors of Neurocognitive Outcomes in Survivors of Pediatric Brain Tumors.

Grob, Sydney T / Miller, Kristen R / Sanford, Bridget / Donson, Andrew M / Jones, Kenneth / Griesinger, Andrea M / Amani, Vladimir / Foreman, Nicholas K / Liu, Arthur / Handler, Michael / Hankinson, Todd C / Milgrom, Sarah / Levy, Jean Mulcahy

Research square

2023

Abstract: Purpose: Neurocognitive deficits are common in pediatric brain tumor survivors. The use of single nucleotide polymorphism (SNP) analysis in DNA repair genes may identify children treated with radiation therapy for brain tumors at increased risk for ... ...

Abstract	Purpose: Neurocognitive deficits are common in pediatric brain tumor survivors. The use of single nucleotide polymorphism (SNP) analysis in DNA repair genes may identify children treated with radiation therapy for brain tumors at increased risk for treatment toxicity and adverse neurocognitive outcomes. Methods: The Human 660W-Quad v1.0 DNA BeadChip analysis (Illumina) was used to evaluate 1048 SNPs from 59 DNA repair genes in 46 subjects. IQ testing was measured by the Wechsler Intelligence Scale for Children. Linear regression was used to identify the 10 SNPs with the strongest association with IQ scores while adjusting for radiation type. Results: The low vs high IQ patient cohorts were well matched for time from first treatment to most recent IQ, first treatment age, gender, and treatments received. 5 SNPs on 3 different genes (CYP29, XRCC1, and BRCA1) and on 3 different chromosomes (10, 19, and 17) had the strongest association with most recent IQ score that was not modified by radiation type. Furthermore, 5 SNPs on 4 different genes (WRN, NR3C1, ERCC4, RAD51L1) on 4 different chromosomes (8, 5, 16, 14) had the strongest association with change in IQ independent of radiation type, first IQ, and years between IQ measures. Conclusions: SNP polymorphisms offer potential to predict adverse neurocognitive outcomes in pediatric brain tumor survivors. Our results require validation in a larger patient cohort. Improving the ability to identify children at risk of treatment related neurocognitive deficits could allow for better treatment stratification and early cognitive interventions.
Language	English
Publishing date	2023-08-07
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3225952/v1
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Article ; Online: A study of knowledge, attitudes, and practices of primary care physicians toward anticoagulant therapy in patients with non-valvular atrial fibrillation in Shanghai, China.

Ye, Shasha / Wang, Tianhao / Liu, Arthur / Yu, Ying / Pan, Zhigang / Gu, Jie

BMC family practice

2020 Volume 21, Issue 1, Page(s) 165

Abstract: Background: As a large number of Community Health Service (CHS) centers in China face the majority of patients with non-valvular atrial fibrillation (NVAF), primary care physicians (PCPs) play a primary role in the prevention of embolization. Therefore, ...

Abstract	Background: As a large number of Community Health Service (CHS) centers in China face the majority of patients with non-valvular atrial fibrillation (NVAF), primary care physicians (PCPs) play a primary role in the prevention of embolization. Therefore, an awareness of anticoagulant management in patients with NVAF must be brought into focus among PCPs in China. This study investigated PCPs' knowledge, attitudes, and practices toward anticoagulant therapy in patients with NVAF, to help them understand their shortcomings regarding oral anticoagulant (OAC) therapy in preventing embolization. Method: This was a cross-sectional observational study of 462 PCPs in CHS centers across Shanghai. We used a self-administered questionnaire to collect data from September to December 2017. A stratified random cluster sampling was adopted in the 90 CHS centers with the family medicine residency program. Result: Among 462 participants, 69.3% (320/462) of females received a medical bachelor's degree and over 50% of participants had more than 10 years of work experience. Each section for knowledge, attitude, and practice were categorized as poor (≤39.0%), fair (40.0-69.0%), and good (≥70.0%). The level of knowledge of OAC therapy for patients with NVAF among PCPs was insufficient in over half (75.8%) of the participants. The majority (89.8%) of PCPs had a positive attitude and 68.0% had modest performance in the anticoagulant management of patients with NVAF. Conclusions: The knowledge and behaviors of PCPs were insufficient for OAC therapy to prevent embolization in patients with NVAF. The study also revealed that there is good potential for PCPs' educational interventions to positively impact the care of patients with NVAF.
MeSH term(s)	Anticoagulants/therapeutic use ; Atrial Fibrillation/drug therapy ; China ; Cross-Sectional Studies ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Physicians, Primary Care ; Practice Patterns, Physicians' ; Stroke
Chemical Substances	Anticoagulants
Language	English
Publishing date	2020-08-15
Publishing country	England
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ISSN	1471-2296
ISSN (online)	1471-2296
DOI	10.1186/s12875-020-01236-4
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Article ; Online: Survivorship Issues in Adolescent and Young Adult Oncology.

Overholser, Linda / Kilbourn, Kristin / Liu, Arthur

The Medical clinics of North America

2017 Volume 101, Issue 6, Page(s) 1075–1084

Abstract: Adolescent and young adult (AYA) individuals with a history of cancer make up a fraction of the total number of cancer survivors in the United States, but they represent a population with needs distinct from either the childhood or the older adult cancer ...

Abstract	Adolescent and young adult (AYA) individuals with a history of cancer make up a fraction of the total number of cancer survivors in the United States, but they represent a population with needs distinct from either the childhood or the older adult cancer populations. Fertility concerns, psychosocial factors, and health care access are just a few of the distinguishing characteristics. Caring for AYA cancer survivors presents unique opportunities for primary care providers to collaborate with oncology colleagues to minimize the long-term cancer burden.
MeSH term(s)	Adolescent ; Counseling ; Fertility ; Health Promotion ; Health Services Accessibility/organization & administration ; Humans ; Mental Health ; Neoplasms/complications ; Neoplasms/psychology ; Primary Health Care/organization & administration ; Referral and Consultation ; Survivors/psychology ; Transition to Adult Care/organization & administration ; United States ; Young Adult
Language	English
Publishing date	2017-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	215710-x
ISSN	1557-9859 ; 0025-7125
ISSN (online)	1557-9859
ISSN	0025-7125
DOI	10.1016/j.mcna.2017.06.002
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Article ; Online: Genetic predictors of neurocognitive outcomes in survivors of pediatric brain tumors.

Journal of neuro-oncology

2023 Volume 165, Issue 1, Page(s) 161–169

Abstract: Background: Neurocognitive deficits are common in pediatric brain tumor survivors. The use of single nucleotide polymorphism (SNP) analysis in DNA repair genes may identify children treated with radiation therapy for brain tumors at increased risk for ... ...

Abstract	Background: Neurocognitive deficits are common in pediatric brain tumor survivors. The use of single nucleotide polymorphism (SNP) analysis in DNA repair genes may identify children treated with radiation therapy for brain tumors at increased risk for treatment toxicity and adverse neurocognitive outcomes. Materials: The Human 660W-Quad v1.0 DNA BeadChip analysis (Illumina) was used to evaluate 1048 SNPs from 59 DNA repair genes in 46 subjects. IQ testing was measured by the Wechsler Intelligence Scale for Children. Linear regression was used to identify the 10 SNPs with the strongest association with IQ scores while adjusting for radiation type. Results: The low vs high IQ patient cohorts were well matched for time from first treatment to most recent IQ, first treatment age, sex, and treatments received. 5 SNPs on 3 different genes (CYP29, XRCC1, and BRCA1) and on 3 different chromosomes (10, 19, and 17) had the strongest association with most recent IQ score that was not modified by radiation type. Furthermore, 5 SNPs on 4 different genes (WRN, NR3C1, ERCC4, RAD51L1) on 4 different chromosomes (8, 5, 16, 14) had the strongest association with change in IQ independent of radiation type, first IQ, and years between IQ measures. Conclusions: SNPs offer the potential to predict adverse neurocognitive outcomes in pediatric brain tumor survivors. Our results require validation in a larger patient cohort. Improving the ability to identify children at risk of treatment related neurocognitive deficits could allow for better treatment stratification and early cognitive interventions.
MeSH term(s)	Child ; Humans ; Brain Neoplasms/complications ; Brain Neoplasms/genetics ; Brain Neoplasms/radiotherapy ; Intelligence Tests ; Survivors ; Cranial Irradiation/adverse effects ; Neuropsychological Tests ; X-ray Repair Cross Complementing Protein 1
Chemical Substances	XRCC1 protein, human ; X-ray Repair Cross Complementing Protein 1
Language	English
Publishing date	2023-10-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	604875-4
ISSN	1573-7373 ; 0167-594X
ISSN (online)	1573-7373
ISSN	0167-594X
DOI	10.1007/s11060-023-04472-7
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