Immunology

Aging (Aging-US)

Aging (Aging-US) published this trending research paper as the cover for Volume 12, Issue 22, entitled, “Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial" by researchers from the Research and Development Unit, Shamir Medical Center, Zerifin, Israel; The Sagol Center for Hyperbaric Medicine and Research, Shamir (Assaf-Harofeh) Medical Center, Zerifin, Israel; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Bar Ilan University, Ramat-Gan, Israel; Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel.

DOI - https://doi.org/10.18632/aging.202188

Corresponding authors - Amir Hadanny - hadannya@shamir.gov.il, and Shai Efrati - efratishai@outlook.com

Abstract:
Introduction: Aging is characterized by the progressive loss of physiological capacity. At the cellular level, two key hallmarks of the aging process include telomere length (TL) shortening and cellular senescence. Repeated intermittent hyperoxic exposures, using certain hyperbaric oxygen therapy (HBOT) protocols, can induce regenerative effects which normally occur during hypoxia. The aim of the current study was to evaluate whether HBOT affects TL and senescent cell concentrations in a normal, non-pathological, aging adult population.

Methods: Thirty-five healthy independently living adults, aged 64 and older, were enrolled to receive 60 daily HBOT exposures. Whole blood samples were collected at baseline, at the 30th and 60th session, and 1-2 weeks following the last HBOT session. Peripheral blood mononuclear cells (PBMCs) telomeres length and senescence were assessed.

Results: Telomeres length of T helper, T cytotoxic, natural killer and B cells increased significantly by over 20% following HBOT. The most significant change was noticed in B cells which increased at the 30th session, 60th session and post HBOT by 25.68%±40.42 (p=0.007), 29.39%±23.39 (p=0.0001) and 37.63%±52.73 (p=0.007), respectively. 

There was a significant decrease in the number of senescent T helpers by -37.30%±33.04 post-HBOT (P<0.0001). T-cytotoxic senescent cell percentages decreased significantly by -10.96%±12.59 (p=0.0004) post-HBOT.

In conclusion, the study indicates that HBOT may induce significant senolytic effects including significantly increasing telomere length and clearance of senescent cells in the aging populations.
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Press release - https://www.aging-us.com/news_room/hyperbaric-oxygen-therapy-impact-on-telomere-length-immunosenescence

Keywords - telomere, senescence, aging, hyperbaric oxygen, length

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at http://www.Aging-US.com​​ and connect with us:

SoundCloud - https://soundcloud.com/Aging-Us
Facebook - https://www.facebook.com/AgingUS/
Twitter - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/agingus​
LinkedIn - https://www.linkedin.com/company/aging/
Pinterest - https://www.pinterest.com/AgingUS/

Aging-US is published by Impact Journals, LLC: http://www.ImpactJournals.com​​

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Trending With Impact: Hyperbaric Oxygen Increases Telomeres and Decreases Senescence

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Oncotarget

Dr. Sandip Pravin Patel, Dr. Karen Yun and Dr. Karen Mccowen from the University of California San Diego, discuss a research paper they co-authored that was published by Oncotarget in Volume 11, Issue 28, entitled, “Rapid onset type 1 diabetes with anti-PD-1 directed therapy.”

DOI - https://doi.org/10.18632/oncotarget.27665

Correspondence to - Sandip Pravin Patel - patel@ucsd.edu

Abstract
Type 1 diabetes is a rare immune-related adverse event (irAE) caused by checkpoint inhibitors with serious risk for diabetic ketoacidosis (DKA). Using our electronic medical record, we identified 1327 adult patients who received PD-(L)1 or CTLA-4 inhibitors from 2013 to 2018. Of the patients who received immunotherapy, 5 (0.38%) patients were found to have type 1 diabetes, all of whom presented with DKA requiring insulin at 20 to 972 days from their first anti-PD-(L)1 dose. All patients were treated with anti-PD-1 therapy (nivolumab or pembrolizumab). Four patients had new onset diabetes with mean HbA1c of 9.1% on DKA presentation and persistent elevations over time. Two patients who tested positive for glutamic acid decarboxylase (GAD) antibodies presented with DKA at 20 and 106 days from first anti-PD-1 administration whereas patients who were autoantibody negative had DKA more than a year later. Type 1 diabetes occurs within a wide time frame after anti-PD-1 initiation and commences with an abrupt course. Our case series suggests that monitoring glycemia in patients on PD-1 inhibitors is not predictive for diabetes occurrence. GAD autoantibodies could portend earlier onset for diabetes, although further prospective studies are needed to elucidate their diagnostic utility and contribution in therapeutic interception.

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Press release - https://www.oncotarget.com/index.php?journal=oncotarget&page=news&op=press&item=oncotarget-rapid-onset-type-1-diabetes-with-anti-pd-1-directed-therap

Keywords - type 1 diabetes, diabetic ketoacidosis (DKA), immune-related adverse event (irAE), immunotherapy, PD-1 inhibitors

About Oncotarget

Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Author Insight: Rare Incidence of Type 1 Diabetes Induced by Immunotherapy

Oncotarget published this trending research paper chosen as the cover for Volume 12, Issue 6, entitled, "Genomic and neoantigen evolution from primary tumor to first metastases in head and neck squamous cell carcinoma," by researchers from the Division of Medical Oncology, Washington University in St. Louis, St. Louis, MO; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO; Department of Pathology and Cell Biology, Columbia University, New York, NY; Division of Hematology/Oncology, Columbia University, New York, NY; Department of Genetics, Washington University in St. Louis, St. Louis, MO; Division of Pediatric Hematology and Oncology, St. Louis Children’s Hospital, St. Louis, MO; Siteman Cancer Center, St. Louis, MO.

Abstract:
Head and neck cell squamous-cell carcinomas (HNSCC) are a group of common cancers typically associated with tobacco use and human papilloma virus infection. Up to half of all cases will suffer a recurrence after primary treatment. As such, new therapies are needed, including therapies which promote the anti-tumor immune response. Prior work has characterized changes in the mutation burden between primary and recurrent tumors; however, little work has characterized the changes in neoantigen evolution. We characterized genomic and neoantigen changes between 23 paired primary and recurrent HNSCC tumors. Twenty-three biopsies from patients originally diagnosed with locally advanced disease were identified from the Washington University tumor bank. Whole exosome sequencing, RNA-seq, and immunohistochemistry was performed on the primary and recurrent tumors. Within these tumors, we identified 6 genes which have predicted neoantigens in 4 or more patients. Interestingly, patients with neoantigens in these shared genes had increased CD3+ CD8+ T cell infiltration and duration of survival with disease. Within HNSCC tumors examined here, there are neoantigens in shared genes by a subset of patients. The presence of neoantigens in these shared genes may promote an anti-tumor immune response which controls tumor progression.

Press release - https://www.oncotarget.com/news/pr/genomic-and-neoantigen-evolution-in-head-and-neck-squamous-cell-carcinoma/

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DOI - https://doi.org/10.18632/oncotarget.27907

Full text - https://www.oncotarget.com/article/27907/text/

Correspondence to - Brian A. Van Tine - bvantine@wustl.edu

Keywords - head and neck squamous cell carcinoma, neoantigens, mutational evolution, tumor relapse, immune cell infiltration

About Oncotarget:

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Paper Spotlight: Genomic and Neoantigen Evolution in Head, Neck Cancer

Creative Biolabs

Welcome to watch Creative Biolabs’ video about immune system and immune therapy. here we share some basic knowledge about T Cell Receptor Engineered T Cell Technology or TCR-T and its application on tumor therapy.
https://www.creative-biolabs.com/car-t/tcr-engineered-t-cell-development.htm

Learn about TCR Technology

Oncotarget published this trending research paper on September 17, 2019, entitled, "Consuming cholera toxin counteracts age-associated obesity" by researchers from the Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA; Department of infectious Diseases and Pathology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Greece.

Abstract:
During the past forty years there has been an inexplicable increase in chronic inflammatory disorders, including obesity. One theory, the ‘hygiene hypothesis’, involves dysregulated immunity arising after too few beneficial early life microbe exposures. Indeed, earlier studies have shown that gut microbe-immune interactions contribute to smoldering inflammation, adiposity, and weight gain. Here we tested a safe and well-established microbe-based immune adjuvant to restore immune homeostasis and counteract inflammation-associated obesity in animal models. We found that consuming Vibrio cholerae exotoxin subunit B (ctB) was sufficient to inhibit age-associated obesogenic outcomes in wild type mice, including reduced crown-like structures (CLS) and granulomatous necrosis histopathology in fat depots. Administration of cholera toxin reduced weight gain irrespective of age during administration; however, exposure during youth imparted greater slenderizing effects when compared with animals receiving ctB for the first time during adulthood. Beneficial effects were transplantable to other obesity-prone animals using immune cells alone, demonstrating an immune-mediated mechanism. Taken together, we concluded that oral vaccination with cholera toxin B helps stimulate health-protective immune responses that counteract age-associated obesity.

Press release - https://www.oncotarget.com/news/pr/consuming-cholera-toxin-counteracts-age-associated-obesity/

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DOI - https://doi.org/10.18632/oncotarget.27137

Full text - https://www.oncotarget.com/article/27137/text/

Correspondence to - Susan E. Erdman - serdman@mit.edu

Keywords - body weight, mouse, exotoxin subunit B, CLS, inflammation

About Oncotarget

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Paper Spotlight: The Cholera Toxin and Inflammation-associated Obesity

Aging (Aging-US) published this trending research paper on July 16, 2020, entitled, "Activation of C-reactive protein proinflammatory phenotype in the blood retinal barrier in vitro: implications for age-related macular degeneration" by researchers from the Group of Ocular Inflammation, Clinical and Experimental Studies, Institut d’Investigacions Biomèdiques Agustí Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain; Department of Life Sciences, Manchester Metropolitan University, Manchester, UK; Cardiovascular Research Center-ICCC, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, CiberCV, Institute Carlos III, Barcelona, Spain; Academic Unit of Ophthalmology, School of Clinical Sciences and School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK; National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital and University College London Institute of Ophthalmology, London, UK.

Abstract:
The retinal pigment epithelium (RPE) is considered one of the main targets of age-related macular degeneration (AMD), the leading cause of irreversible vision loss among the ageing population worldwide. Persistent low grade inflammation and oxidative stress eventually lead to RPE dysfunction and disruption of the outer blood-retinal barrier (oBRB). Increased levels of circulating pentameric C-reactive protein (pCRP) are associated with higher risk of AMD. The monomeric form (mCRP) has been detected in drusen, the hallmark deposits associated with AMD, and we have found that mCRP induces oBRB disruption. However, it is unknown how mCRP is generated in the subretinal space. Using a Transwell model we found that both pCRP and mCRP can cross choroidal endothelial cells and reach the RPE in vitro and that mCRP, but not pCRP, is able to cross the RPE monolayer in ARPE-19 cells. Alternatively, mCRP can originate from the dissociation of pCRP in the surface of lipopolysaccharide-damaged RPE in both ARPE-19 and primary porcine RPE lines. In addition, we found that the proinflammatory phenotype of mCRP in the RPE depends on its topological localization. Together, our findings further support mCRP contribution to AMD progression enhancing oBRB disruption.

Special collection on eye disease - https://www.aging-us.com/special-collections-archive/eye-disease

Press release - https://www.aging-us.com/news_room/activation-of-c-reactive-protein-proinflammatory-phenotype-in-the-blood-retinal-barrier-in-vitro-implications-for-age-related-macular-degeneration

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DOI - https://doi.org/10.18632/aging.103655

Full text - https://www.aging-us.com/article/103655/text

Correspondence to: Blanca Molins email: bmolins@clinic.cat

Keywords: age-related macular degeneration, retinal pigment epithelium, inflammation, C-reactive protein

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at http://www.Aging-US.com​​ or connect with us on:

SoundCloud - https://soundcloud.com/Aging-Us
Facebook - https://www.facebook.com/AgingUS/
Twitter - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/agingus​
LinkedIn - https://www.linkedin.com/company/aging/
Pinterest - https://www.pinterest.com/AgingUS/

Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls

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Paper Spotlight: Age-related Macular Degeneration and C-reactive Protein

Oncotarget published this trending research paper on May 26, 2020, entitled, "An exploratory study of metformin with or without rapamycin as maintenance therapy after induction chemotherapy in patients with metastatic pancreatic adenocarcinoma" by researchers from the Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD; The Skip Viragh Center for Pancreas Cancer at Johns Hopkins, Baltimore, MD; Virginia Piper Cancer Center at HonorHealth, Scottsdale, AZ; Molecular Medicine Division, Translational Genomics Research Institute (TGen), Phoenix, AZ; Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Department of Nuclear Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai City, China; The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD.

Abstract:
Purpose: Metformin combined with the mTOR inhibitor rapamycin showed potential synergistic anti-tumor activity in preclinical studies in pancreatic ductal adenocarcinoma (PDA). This phase 1b study (NCT02048384) was conducted to evaluate the feasibility and activity of metformin +/– rapamycin in the maintenance setting for unselected patients with metastatic PDA (mPDA) treated with chemotherapy.

Materials and Methods: Eligible patients with stable or responding mPDA after ≥ 6 months on chemotherapy were randomized 1:1 to metformin alone (Arm A) or with rapamycin (Arm B), stratified by prior treatment with FOLFIRINOX. Fluorodeoxyglucose (FDG) PET scans and peripheral blood mononuclear cells were obtained for exploratory analyses.

Results: 22 subjects (11 per arm) received treatment per protocol. Median PFS/OS were 3.5 and 13.2 months respectively, with 2 year OS rate of 37%; there were no differences between arms. No responses were observed by RECIST; however, decreases in FDG avidity and/or CA19-9 were observed in several long-term survivors. Treatment related adverse events of Grade ≥ 3 occurred in 0% vs 27% of patients in Arm A vs B and were asymptomatic hematologic or electrolyte abnormalities that were not clinically significant. Improved survival was associated with low baseline neutrophil: lymphocyte ratio, baseline lack of assessable disease by PET, and greater expansion of dendritic cells following treatment.

Conclusions: Metformin +/– rapamycin maintenance for mPDA was well-tolerated and several patients achieved stable disease associated with exceptionally long survival. Further prospective studies are needed to clarify the role of these agents in the maintenance setting and to enhance patient selection for such approaches.

Press release - https://www.oncotarget.com/news/pr/an-exploratory-study-of-metformin-and-rapamycin-as-maintenance-therapy/

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DOI - https://doi.org/10.18632/oncotarget.27586

Full text - https://www.oncotarget.com/article/27586/text/

Correspondence to - Dung T. Le - dle@jhmi.edu
 
Keywords - pancreatic cancer, mTOR inhibition, maintenance therapy, metformin, rapamycin

About Oncotarget

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Paper Spotlight: Effects of Metformin and Rapamycin in Pancreatic Cancer

Oncotarget published this trending research paper in Volume 12, Issue 24, entitled, "Circulating low density neutrophils of breast cancer patients are associated with their worse prognosis due to the impairment of T cell responses" by researchers from iNOVA4Health, CEDOC, NOVA Medical School (NMS), Universidade Nova de Lisboa, Lisbon, Portugal; Instituto CUF de Oncologia, Lisbon, Portugal.

Abstract:
Neutrophils are prominent immune components of tumors, having either anti-tumor (N1) or pro-tumor activity (N2). Circulating neutrophils, divided into high density neutrophils (HDN) and low density neutrophils (LDN), functionally mirror those N1 and N2 cells, respectively. LDN are rare in non-pathological conditions, but frequent in cancer, exhibiting a pro-tumor phenotype. These findings have been mainly demonstrated in animal models, thus proper validation in humans is still imperative. Here, we observed that LDN were increased in the blood of breast cancer (BC) patients, particularly with metastatic disease. Within the population of non-metastatic patients, LDN were more prevalent in patients with poor response to neoadjuvant chemotherapy than patients with a good response. The higher incidence of LDN in BC patients with severe disease or resistance to treatment can be explained by their pro-tumor/immunosuppressive characteristics. Moreover, the percentage of LDN in BC patients’ blood was negatively correlated with activated cytotoxic T lymphocytes and positively correlated with immunosuppressive regulatory T cells. The ability of LDN to spoil anti-tumor immune responses was further demonstrated ex vivo. Hence, this study reveals the potential of LDN as a biomarker of BC response to treatment and opens new avenues for developing new immunotherapies.

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DOI - https://doi.org/10.18632/oncotarget.28135

Full text - https://www.oncotarget.com/article/28135/text/

Correspondence to - M. Guadalupe Cabral - guadalupe.cabral@nms.unl.pt

Keywords - breast cancer, chemotherapy response, tumor-associated neutrophils, low density neutrophils, biomarker

About Oncotarget

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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