COVID-19 and Cancer最新文献

{"title":"Abstract 710: Androgen-deprivation therapy boosts MX1 expression, a silent effector against COVID-19","authors":"J. Bizzotto, P. Sanchis, S. Lage-Vickers, R. Lavignolle, Agustina Ayelen Sabater, M. Abbate, A. Toro, Florencia Cascardo, S. Olszevicki, N. Anselmino, E. Labanca, Emiliano G. Ortiz, E. Vazquez, J. Cotignola, G. Gueron","doi":"10.1158/1538-7445.AM2021-710","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-710","url":null,"abstract":"Cancer is a risk factor for SARS-CoV-2 infection. Recent reports have shown that prostate cancer (PCa) patients undergoing androgen-deprivation therapies (ADT) were partially protected from COVID-19. The human myxovirus resistance gene 1 (MX1) is expressed in many tissues, including prostate, and we have previously demonstrated its antitumoral activity in PCa. This protein participates in the antiviral response and it is an IFN-stimulated gene (ISGs), especially during influenza virus infection. There are ongoing clinical trials for COVID-19 prevention and/or treatment using type I or III interferons. However, IFN administration could enhance a \"cytokine-storm\" causing a hyper-inflammatory response and contributing to organ failure. In this work, we performed bioinformatics analyses in a case-control study from SARS-CoV-2 positive (n=403) and negative (n=50) patients. We analyzed the response to infection assessing gene expression profiles in nasopharyngeal swabs of key host cell receptors (ACE2, TMPRSS2, BSG/CD147, CTSB, CTSL, ADAM17) and antiviral proteins (MX1, MX2, NRF2, IRF3, HIF1A, HMOX1).SARS-CoV-2 positive cases had higher ACE2, but lower TMPRSS2, BSG/CD147 and CTSB expression. Patient age negatively affected ACE2 expression. MX1 and MX2 were higher in SARS-CoV-2 positive individuals, and negative trends were observed as patients9 age increased. Principal Component Analysis determined that ACE2, MX1, MX2 and BSG/CD147 expressions were able to cluster non-COVID-19 and COVID-19 individuals. Multivariable regression showed that MX1 expression significantly increased for each unit of viral load increment.Given that MX1 was differentially expressed between COVID-19 and non-COVID-19 patients, we evaluated MX1 expression in A549 and Calu3 lung cell lines. MX1 was significantly up-regulated upon infection with SARS-CoV-2.Since ADT reduces SARS-CoV-2 infection incidence, we aim to study MX1 regulation by dihydrotestosterone (DHT). We browsed publicly available ChIP-seq experiments evaluating androgen receptor (AR) binding sites in different PCa cell lines under DHT stimulation. Results indicated enriched AR binding sites on the MX1 sequence. Therefore, we treated LNCaP cells with DHT, observing a significant decrease in MX1 mRNA levels. Accordingly, we observed a significant increase of MX1 gene expression in PCa patients after ADT treatment.In summary, our study findings support differences in ACE2, MX1, MX2 and BSG/CD147 expression between COVID-19 and non-COVID-19 patients; and point out to MX1 as a critical responder in SARS-CoV-2 infection. Furthermore, we demonstrated MX1 modulation by ADT. Taking into consideration the fact that PCa patients that underwent ADT were less prone to present the infection, we propose this gene as an alternative druggable target for COVID-19 patients, especially those with PCa as a previous condition. Citation Format: Juan Antonio Bizzotto, Pablo Sanchis, Sofia Lage-Vickers, Rosario Lavignolle, Agustina Sabater, ","PeriodicalId":417728,"journal":{"name":"COVID-19 and Cancer","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125293595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 716: Telehealth use among multiple myeloma patients during the COVID-19 pandemic","authors":"Nathan W. Sweeney, S. Goldsmith, Jenny Ahlstrom","doi":"10.1158/1538-7445.AM2021-716","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-716","url":null,"abstract":"Background:The rapid outbreak of coronavirus disease 2019 (COVID-19) led to delays of non-urgent or routine medical care. Regulatory waivers and policy changes from the Centers of Medicare and Medicaid Services (CMS) for the use of telehealth came as a solution to help fight the outbreak. The aim of this project was to survey the change in the frequency of use of telehealth services among multiple myeloma (MM) patients during the COVID-19 pandemic. Methods:We utilized HealthTree Cure Hub For Multiple Myeloma (healthree.org) and invited patients with active MM cancer or precursor conditions to participate in an online survey. We analyzed patient responses to doctor visits, the use of telehealth before and after the COVID-19 pandemic, and whether they had sufficient access to their doctor. Results:1,301 MM pts participated in the survey between April 15, 2020, and June 8, 2020. During the pandemic, 36% of patients indicated visiting with their physician less often than before, 2% visited more often, and 62% had no change in the frequency of their visits. The percent of patients responding “Sometimes” or “Yes” to the use of telehealth are reported here. Before the pandemic, 10% of patients used telehealth, while 62% of patients indicated using telehealth during the pandemic, a 523% increase. When asked if they had sufficient access to their MM healthcare provider 90% of patients indicated that they did, while 10% indicated they did not. Conclusions:There were significantly fewer in-person visits during the COVID-19 pandemic likely due to the CDC-recommended physical distancing practices. During this time, telehealth use among MM patients dramatically increased compared to telehealth use before the pandemic. It is reasonable to assume that patients indicated having sufficient access to their healthcare provider as a result of patients receiving care through telehealth visits. The authors encourage readers to think more broadly about the benefits of telehealth. Maintaining sufficient access to one healthcare provider addressed in this abstract is only a fraction of the benefits telehealth offers. MM is a rare cancer and as a result, some states have few if any specialists. Maintaining telehealth policy changes made during the pandemic would remove geographical barriers and open access to specialists across the country. Citation Format: Nathan W. Sweeney, Scott R. Goldsmith, Jennifer M. Ahlstrom. Telehealth use among multiple myeloma patients during the COVID-19 pandemic [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 716.","PeriodicalId":417728,"journal":{"name":"COVID-19 and Cancer","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129212635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 715: Flow cytometry analysis of immune response to COVID-19 vaccine candidates using anin vitrostimulation model","authors":"Xiaoshan Shi, S. Bornheimer, Suraj Saksena, S. Widmann, A. Tyznik","doi":"10.1158/1538-7445.AM2021-715","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-715","url":null,"abstract":"T cell immunity is vital for the control of viral infections. Cytotoxic CD8 T cells play a crucial role in eliminating virus-infected cells while CD4 helper T cells mediate host immune responses and promote B cells to secrete antibodies. For both, T cell recognition of viral antigens in the form of short peptides presented by HLA complexes is a prerequisite for T cell activation. Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has become a global pandemic that has disrupted economies and resulted in an enormous burden on health care systems. Despite the worldwide intensive efforts on development of COVID-19 therapeutics, a safe and effective COVID-19 treatment or vaccine is not yet available. In this study, we established an in vitro stimulation system in which peripheral blood mononuclear cells were treated with putative SARS-CoV-2 immunogenic peptides. T cell immune responses were measured using different quantitative flow cytometry panels that were designed for evaluating cytokine production or identifying T cell subsets. Evaluation of host immune responses with a suite of flow cytometric panels may prove to be useful in the study of COVID-19. For Research Use Only. Not for use in diagnostic or therapeutic procedures. Class 1 Laser Product.BD-23276 (v1.0) 1120BD and the BD Logo are trademarks of Becton, Dickinson and Company. © 2020 BD. All rights reserved. Citation Format: Xiaoshan Shi, Scott J. Bornheimer, Suraj Saksena, Stephanie Widmann, Aaron Tyznik. Flow cytometry analysis of immune response to COVID-19 vaccine candidates using an in vitro stimulation model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 715.","PeriodicalId":417728,"journal":{"name":"COVID-19 and Cancer","volume":"189 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116606686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 719: The emergence of the COVID-19 pandemic and its impact on a novel cancer care delivery model at Federally Qualified Health Centers","authors":"Nicolás O. Francone, William J. Dunne, J. Alhalel, Sankirtana M Danner, Nihmotallahi Adebayo, T. Madorsky, Cassandra Osei, Juan P. Rivera, Julia Trossman, C. Weldon, Elizabeth Adetoro, Melissa A Simon","doi":"10.1158/1538-7445.AM2021-719","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-719","url":null,"abstract":"","PeriodicalId":417728,"journal":{"name":"COVID-19 and Cancer","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127558045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 706: Rapid detection of SARS-CoV-2 antigen and antibody seroconversion in clinical specimens using a novel Surface Programmable Activation Receptor (SPAR) modified T cell diagnostic method","authors":"Aaron K. LeFebvre, Melissa Frenchmeyer, K. McQuaid, M. Williams, Charles Mcbrairty, J. Kittle","doi":"10.1158/1538-7445.AM2021-706","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-706","url":null,"abstract":"Infection by SARS-CoV-2 virus or past exposure to COVID19, is of central concern to the management of cancer patient co-morbidities. Currently available testing methods require separate technologies to determine if a patient has anti- SARS-CoV-2 antibodies or if they are currently infected. A rapid, reliable, dual-use diagnostic platform deployed near the cancer patient would make a critical contribution to their care. We previously developed a biomarker detection system using modified Jurkat-T cells engineered into specific and sensitive biosensors that display a wide dynamic range with low background signal. In this system, the T cell receptor (TCR) is fused to an antibody binding domain (mouse FcγRI) and the cells are also engineered to express a high level of the calcium dependent photoprotein, aequorin. The modified TCR can be programmed for detection of a target of interest by addition of specific and appropriately tagged target detection molecules (TDMs) which bind the FcγRI.Using this system, we have developed novel assays specific for detection of SARS-CoV-2 antigen or serum antibodies against SARS-CoV-2 in clinical specimens, using mouse IgG2a-tagged TDMs provided by Twist Bioscience. For antigen detection, mouse IgG2a-Fc tagged SARS-CoV-2 spike antibody (IgG) was used as the assay TDM, sensitizing the cells to SARS-CoV-2 spike protein. For antibody detection, mouse IgG2a-Fc tagged SARS-CoV-2 spike protein (S1 domain) was used as the assay TDM with T cell activation caused by binding to serum antibodies against SARS-CoV-2 spike protein. Following binding of either target, T cell activation causes a rapid release of calcium in the modified T cells, leading to a rapid light emission by aequorin in the presence of coelenterazine, CTZ. This light emission is detectable in less than 5 minutes using a simple luminometer, and with no specimen pre-treatment. Results from both contrived and clinical specimens using each diagnostic method will be presented to demonstrate their accuracy, reproducibility, sensitivity, specificity, and speed. Results are highly reproducible at sub-nanomolar spike protein concentrations in viral transport media (VTM) and human serum, respectively. Real-world clinical seropositive specimens from convalescent COVID-19 patients as well as serum from patients exposed to related viruses or other disease states were tested using the antibody detection assay. Gamma-irradiated clinical SARS-CoV-2 isolate as well as related and unrelated viral isolates on nasal swabs were tested using the antigen detection assay. Citation Format: Aaron K. LeFebvre, Melissa Frenchmeyer, Kyle M. McQuaid, MRussell Williams, Charles M. McBrairty, Joseph D. Kittle. Rapid detection of SARS-CoV-2 antigen and antibody seroconversion in clinical specimens using a novel Surface Programmable Activation Receptor (SPAR) modified T cell diagnostic method [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 A","PeriodicalId":417728,"journal":{"name":"COVID-19 and Cancer","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127129974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}