tbuckley/cabot-search huggingface dataset:
Why I . . . am a Brownie leader
Authors: Marika Davies
Journal: BMJ (2021)

<b>Background:</b> The myotonic dystrophies (DM1, DM2) are the most common adult muscle diseases and are characterized by multisystem involvement. DM1 has been described in diverse populations, whereas DM2 seems to occur primarily in European Caucasians. Both are caused by the expression of expanded microsatellite repeats. In DM1, there is a reservoir of premutation alleles; however, there have been no reported premutation alleles for DM2. The (CCTG)<sub>DM2</sub> expansion is part of a complex polymorphic repeat tract of the form (TG)<sub>n</sub>(TCTG)<sub>n</sub>(CCTG)<sub>n</sub>(NCTG)<sub>n</sub>(CCTG)<sub>n</sub>. Expansions are as large as 40 kb, with the expanded (CCTG)<sub>n</sub> motif uninterrupted. Reported normal alleles have up to (CCTG)<sub>26</sub> with one or more interruptions. <b>Methods:</b> To identify and characterize potential DM2 premutation alleles, we cloned and sequenced 43 alleles from 23 individuals. Uninterrupted alleles were identified, and their instability was confirmed by small-pool PCR. We determined the genotype of a nearby single nucleotide polymorphism (rs1871922) known to be in linkage disequilibrium with the DM2 mutation. <b>Results:</b> We identified three classes of large non-DM2 repeat alleles: 1) up to (CCTG)<sub>24</sub> with two interruptions, 2) up to (CCTG)<sub>32</sub> with up to four interruptions, and 3) uninterrupted (CCTG)<sub>22–33</sub>. Large non-DM2 alleles were more common in African Americans than in European Caucasians. Uninterrupted alleles were significantly more unstable than interrupted alleles (<i>p</i> = 10<sup>−4</sup> to 10<sup>−7</sup>). Genotypes at rs1871922 were consistent with the hypothesis that all large alleles occur on the same haplotype as the DM2 expansion. <b>Conclusions:</b> We conclude that unstable uninterrupted (CCTG)<sub>22-33</sub> alleles represent a premutation allele pool for DM2 full mutations.
Potent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite
Authors: Gabriele Cerutti, Yicheng Guo, Tongqing Zhou, Jason Gorman, Myungjin Lee, Micah Rapp, Eswar R. Reddem, Jian Yu, Fabiana Bahna, Jude Bimela, Yaoxing Huang, Phinikoula S. Katsamba, Lihong Liu, Manoj S. Nair, Reda Rawi, Adam S. Olia, Pengfei Wang, Baoshan Zhang, Gwo-Yu Chuang, David D. Ho, Zizhang Sheng, Peter D. Kwong, Lawrence Shapiro
Journal: Cell Host & Microbe (2021)
Infliximab at diagnosis: moving towards personalisation in paediatric inflammatory bowel disease
Authors: James J Ashton, Sarah Ennis, R Mark Beattie
Journal: Gut (2021)

The optimal strategy for induction of remission in paediatric Crohn’s disease, and in particular the timing of introduction of monoclonal antibody therapy, remains controversial. This has long-term implications in a condition where short-term benefit, including impact on growth, must be balanced against the potential need for treatment escalation and risks associated with therapy. This is not helped by the fact the condition is heterogeneous in type, distribution and severity. International guidance currently recommends that children presenting with moderate to severe luminal disease are commenced on exclusive enteral nutrition (EEN), oral corticosteroids, intravenous corticosteroids or anti-TNF therapy, with widespread use of EEN as first line.1

In their ground-breaking article, Jongsma et al describe the use of anti-TNF therapy for induction of remission, and compare this to ‘conventional’ therapy in an open-label randomised control trial.2 All patients had moderate to severe disease. The data are novel and have the potential to inform practice. Rather than focusing on the continued debate between top-down versus step-up therapy, these data inform paediatric gastroenterologists on the utility of induction therapy with infliximab, with the protocol dictating patients who are able should stop the drug after the final infusion at 22 weeks. The results of the study, conducted on 100 patients, highlight the efficacy of infliximab (59%) to …
P36.01 KEAP1 and NRF2 Mutations in Hispanic and Non-Hispanic Patients with NSCLC: Clinicopathologic Characteristics and Prognosis.
Authors: E. Rodriguez, K. Khan, T. Torres, R. Dawar, K. Gawri, C. Ikpeazu, G. Lopes
Journal: Journal of Thoracic Oncology (2021)
Association Between Antiangiogenic Drugs Used for Cancer Treatment and Artery Dissections or Aneurysms
Authors: Joris Guyon, Amandine Gouverneur, Sandy Maumus-Robert, Xavier Bérard, Antoine Pariente, Andreas Bikfalvi, Pernelle Noize
Journal: JAMA Oncology (2021)

This pharmacovigilance study uses data from the World Health Organization database of adverse drug reactions to examine the association of antiangiogenic drugs with artery dissections or aneurysms among patients receiving antiangiogenic drugs for the treatment of cancer.
When steroids are not enough in immune-related hepatitis: current clinical challenges discussed on the basis of a case report
Authors: Marie-Léa Gauci, Barouyr Baroudjian, Celeste Lebbe, Olivier Roux
Journal: Journal for ImmunoTherapy of Cancer (2021)

Immune-related hepatitis (IRH) is a frequent but poorly understood immune-related adverse event and its frequency increases since the use of combination therapy in several cancer types. Therefore, there is an urgent need to develop adapted guidelines to manage IRH.In the present letter, based on Ziogas et al report entitled 'When steroids are not enough in immune-related hepatitis: current clinical challenges discussed on the basis of a case report', several points are discussed: assessment of IRH severity and liver biopsy indication, immune-related cholangitis as a differential diagnosis for some IRH presentation, the need of steroids for IRH management or the indication for second line immunosuppressive treatment and finally, the possibility of immunotherapy resumption.
P09.50 Lung Cancer Hospitalization Burden. Generating Knowledge from Administrative Data to Optimize Management
Authors: J. Sanchez, B. Nunez-Garcia, M. Blanco Clemente, J. Cruz-Bermudez, M. Mendez, B. Cantos, Y. Garitaonaindía, A. Ramos Martin-Vegue, V. Calvo, M. Provencio
Journal: Journal of Thoracic Oncology (2021)
Pharmacologic and hormonal treatments for menopausal sleep disturbances: A network meta-analysis of 43 randomized controlled trials and 32,271 menopausal women
Authors: Yu-Shian Cheng, Ping-Tao Tseng, Ming-Kung Wu, Yu-Kang Tu, Yi-Cheng Wu, Dian-Jeng Li, Tien-Yu Chen, Kuan-Pin Su, Brendon Stubbs, Andre F. Carvalho, Pao-Yen Lin, Yutaka J. Matsuoka, Yen-Wen Chen, Cheuk-Kwan Sun, Yow-Ling Shiue
Journal: Sleep Medicine Reviews (2021)
What Is the Antibody Response and Role in Conferring Natural Immunity After SARS-CoV-2 Infection? Rapid, Living Practice Points From the American College of Physicians (Version 1)
Authors: Amir Qaseem, Jennifer Yost, Itziar Etxeandia-Ikobaltzeta, Mary Ann Forciea, George M. Abraham, Matthew C. Miller, Adam J. Obley, Linda L. Humphrey
Journal: Annals of Internal Medicine (2021)

An updated version of this article was published on 25 January 2022.
Evaluation of a Strength-Training Program on Clinical Outcomes in Older Adults—Reply
Authors: Heike A. Bischoff-Ferrari, Robert Theiler, Caroline de Godoi Rezende Costa Molino
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Non-invasive peripheral vascular function, incident cardiovascular disease, and mortality in the general population
Authors: Renate B Schnabel, Christina Magnussen, Andreas Schulz, Francisco M Ojeda, Volker H Schmitt, Natalie Arnold, Christoph R Sinning, Manfred E Beutel, Irene Schmidtmann, Norbert Pfeiffer, Anja Leuschner, Karl J Lackner, Tommaso Gori, Emelia J Benjamin, Harald Binder, Philipp S Wild, Stefan Blankenberg, Thomas Münzel
Journal: Cardiovascular Research (2021)

Evidence suggests that peripheral vascular function is related to cardiovascular disease (CVD) and mortality. We evaluated the associations of non-invasive measures of flow-mediated dilatation and peripheral arterial tonometry with incident CVD and mortality.In a post-hoc analysis of the community-based Gutenberg Health Study, median age 55 years (25th/75th percentile 46/65) and 49.5% women, we measured brachial artery flow-mediated dilatation (N=12 599) and fingertip peripheral arterial tonometry (N=11 125). After a follow-up of up to 11.7 years, we observed 595 incident CVD events, 106 cardiac deaths, and 860 deaths in total. Survival curves showed decreased event-free survival with higher mean brachial artery diameter and baseline pulse amplitude and better survival with higher mean flow-mediated dilatation and peripheral arterial tonometry ratio (all Plog rank <0.05). In multivariable-adjusted Cox regression analyses only baseline pulse amplitude was inversely related to mortality [hazard ratio (HR) per standard deviation increase, 0.86, 95% confidence interval (95% CI), 0.79-0.94; P=0.0009]. After exclusion of individuals with prevalent CVD the association was no longer statistically significant in multivariable-adjusted models (HR 0.91, 95% CI 0.81-1.02; P=0.11). None of the vascular variables substantially increased the C-index of a model comprising clinical risk factors.In our cohort, non-invasive measures of peripheral vascular structure and function did not reveal clinically relevant associations with incident CVD or mortality. Whether determination of pulse amplitude by peripheral arterial tonometry improves clinical decision-making in primary prevention needs to be demonstrated.
Evaluating Polygenic Risk Scores for Breast Cancer in Women of African Ancestry
Authors: Zhaohui Du, Guimin Gao, Babatunde Adedokun, Thomas Ahearn, Kathryn L Lunetta, Gary Zirpoli, Melissa A Troester, Edward A Ruiz-Narváez, Stephen A Haddad, Parichoy PalChoudhury, Jonine Figueroa, Esther M John, Leslie Bernstein, Wei Zheng, Jennifer J Hu, Regina G Ziegler, Sarah Nyante, Elisa V Bandera, Sue A Ingles, Nicholas Mancuso, Michael F Press, Sandra L Deming, Jorge L Rodriguez-Gil, Song Yao, Temidayo O Ogundiran, Oladosu Ojengbe, Manjeet K Bolla, Joe Dennis, Alison M Dunning, Douglas F Easton, Kyriaki Michailidou, Paul D P Pharoah, Dale P Sandler, Jack A Taylor, Qin Wang, Clarice R Weinberg, Cari M Kitahara, William Blot, Katherine L Nathanson, Anselm Hennis, Barbara Nemesure, Stefan Ambs, Lara E Sucheston-Campbell, Jeannette T Bensen, Stephen J Chanock, Andrew F Olshan, Christine B Ambrosone, Olufunmilayo I Olopade, Joel Yarney, Baffour Awuah, Beatrice Wiafe-Addai, David V Conti, Julie R Palmer, Montserrat Garcia-Closas, Dezheng Huo, Christopher A Haiman
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Polygenic risk scores (PRSs) have been demonstrated to identify women of European, Asian, and Latino ancestry at elevated risk of developing breast cancer (BC). We evaluated the performance of existing PRSs trained in European ancestry populations among women of African ancestry. Methods We assembled genotype data for women of African ancestry, including 9241 case subjects and 10 193 control subjects. We evaluated associations of 179- and 313-variant PRSs with overall and subtype-specific BC risk. PRS discriminatory accuracy was assessed using area under the receiver operating characteristic curve. We also evaluated a recalibrated PRS, replacing the index variant with variants in each region that better captured risk in women of African ancestry and estimated lifetime absolute risk of BC in African Americans by PRS category. Results For overall BC, the odds ratio per SD of the 313-variant PRS (PRS313) was 1.27 (95% confidence interval [CI] = 1.23 to 1.31), with an area under the receiver operating characteristic curve of 0.571 (95% CI = 0.562 to 0.579). Compared with women with average risk (40th-60th PRS percentile), women in the top decile of PRS313 had a 1.54-fold increased risk (95% CI = 1.38-fold to 1.72-fold). By age 85 years, the absolute risk of overall BC was 19.6% for African American women in the top 1% of PRS313 and 6.7% for those in the lowest 1%. The recalibrated PRS did not improve BC risk prediction. Conclusion The PRSs stratify BC risk in women of African ancestry, with attenuated performance compared with that reported in European, Asian, and Latina populations. Future work is needed to improve BC risk stratification for women of African ancestry.
Lipoprotein (a) levels and risk of coronary heart disease: large-scale prospective data
Authors: A. Bennet, J. Danesh, E. Di Angelantonio, S. Erquo, G. Eiriksdottir, G. Sigurdsson, Mark Woodward, A. G. Rumley, G. D. O. Lowe, V. Gudnason
Journal: JAMA Internal Medicine (2008)
HSR21-069: Factors Associated With Time to Treatment With an EGFR-TKI Among Patients With Non-Squamous Metastatic Non-Small Cell Lung Cancer: A SEER-Medicare Analysis
Authors: Chunlin Qian, Elizabeth Marrett, Winghan Jacqueline Kwong, Laura Q.M. Chow
Journal: Journal of the National Comprehensive Cancer Network (2021)

"HSR21-069: Factors Associated With Time to Treatment With an EGFR-TKI Among Patients With Non-Squamous Metastatic Non-Small Cell Lung Cancer: A SEER-Medicare Analysis" published on 17 Mar 2021 by National Comprehensive Cancer Network.
HSR21-071: Healthcare Utilization Between Blood and Solid Cancer Survivors and Implications for Financial Toxicity: Results From the National Health Interview Survey, 2009-2018
Authors: Christopher T. Su, Minal R. Patel
Journal: Journal of the National Comprehensive Cancer Network (2021)

"HSR21-071: Healthcare Utilization Between Blood and Solid Cancer Survivors and Implications for Financial Toxicity: Results From the National Health Interview Survey, 2009-2018" published on 17 Mar 2021 by National Comprehensive Cancer Network.
Abstract 3068: Intra-left Ventricular Contractile Dyssynchrony As An Independent Determinant Of Left Atrial Remodeling In Patients With Atrial Fibrillation Managed by Catheter-based Circumferential Pulmonary Venous Isolation
Authors: FU-CHUN CHIU, Yi-Chih Wang, Chih-Chieh Yu, Ling-Ping Lai, Juey-Jen Hwang, Chia-Ti Tsai, Chuen-Den Tseng, Rodolphe P. Katra, Jiunn-Lee Lin
Journal: Circulation (2007)

BACKGROUND. Enlarged left atrial volume (LAV), resulting from multifactorial pathogenesis, carries a poorer prognosis to patients with atrial fibrillation (AF) even under well rhythm control. We hypothesized that the preexistence of intra-left ventricular (LV) contractile dyssynchrony impaired diastolic filling, which contribute to atrial remodeling in AF patients. METHODS. We investigated 40 patients (34 men and 6 women, mean age 60 ± 10 years) with paroxysmal or persistent AF who were converted mainly by catheter ablation-based circumferential pulmonary venous isolation and then pharmacologically maintained in sinus rhythm. Exclusion criteria included significant (&gt;moderate) valvular heart disease, LV ejection fraction &lt;55 %, or ischemic heart disease confirmed by positive stress tests or coronary angiography. The LAV was measured by 2D echocardiography [π×D1×D2×D3/6 from parasternal long-axis view (D1) and apical four-chamber view (D2 &amp; D3)]. The peak myocardial systolic velocity (S M ) and the time to peak S M (T S ) of the 6-basal and 6-mid LV segments were measured by tissue Doppler imaging (TDI). RESULTS. With similar AF duration before conversion, patients with LAV &gt;40ml (n = 16) had similar baseline characteristics, cardiovascular medications, QRS width, and LV chamber sizes as those with LAV &lt;40ml (n = 24). However, TDI showed the mean S M was borderline lower (6.3 ± 1.2 vs. 7.1 ± 1.2 cm/s, p &lt; 0.05), and the maximal intersegmental difference in T S (77 ± 43 vs. 40 ± 22 ms, p &lt; 0.003) was greater in patients with larger LAV. The intersegmental difference in T S correlated positively with LAV (r = 0.41, p &lt; 0.009), and LV filling pressure estimated by early transmitral flow velocity/annular diastolic velocity was significantly higher (12.3 ± 7.8 vs. 8.7 ± 2.2, p &lt; 0.045) in patients with intersegmental difference in T S &gt;65 ms. After adjusting for age, gender, and the diastolic parameters, intersegmental difference in T S &gt;65ms emerged as an independent determinant of larger LAV in multivariate logistic analysis (OR=17; 95% CI=2–166, p &lt; 0.016). CONCLUSIONS. Intraventricular dyssynchrony, which accompanied with elevated LV filling pressure, contributed independently to LA remodeling in AF patients converted into sinus rhythm by catheter ablation.
P09.32 Is the New Patient Respiratory Appointment an Appropriate Time to Refer Patients With Likely Lung Cancer for Prehabilitation?
Authors: L. Glanville, I. Phillips, M. Mackean, P. Reid, F. Boellert, J. Mencnarowski, D. Borthwick, F. Little, K. Maclennan, A. Tufail, T. Evans, C. Barrie, S. Campbell
Journal: Journal of Thoracic Oncology (2021)
Pacritinib Combined with Sirolimus and Low-Dose Tacrolimus for GVHD Prevention after Allogeneic Hematopoietic Cell Transplantation: Preclinical and Phase I Trial Results
Authors: Joseph Pidala, Kelly Walton, Hany Elmariah, Jongphil Kim, Asmita Mishra, Nelli Bejanyan, Taiga Nishihori, Farhad Khimani, Lia Perez, Rawan G. Faramand, Marco L. Davila, Michael L. Nieder, Elizabeth M. Sagatys, Shernan G. Holtan, Nicholas J. Lawrence, Harshani R. Lawrence, Bruce R. Blazar, Claudio Anasetti, Said M. Sebti, Brian C. Betts
Journal: Clinical Cancer Research (2021)

Abstract Purpose: In this first-in-human, phase I, GVHD prevention trial (NCT02891603), we combine pacritinib (PAC), a JAK2 inhibitor, with sirolimus to concurrently reduce T-cell costimulation via mTOR and IL6 activity. We evaluate the safety of pacritinib when administered with sirolimus plus low-dose tacrolimus (PAC/SIR/TAC) after allogeneic hematopoietic cell transplantation. Patients and Methods: The preclinical efficacy and immune modulation of PAC/SIR were investigated in xenogeneic GVHD. Our phase I trial followed a 3+3 dose-escalation design, including dose level 1 (pacritinib 100 mg daily), level 2 (pacritinib 100 mg twice daily), and level 3 (pacritinib 200 mg twice daily). The primary endpoint was to identify the lowest biologically active and safe dose of pacritinib with SIR/TAC (n = 12). Acute GVHD was scored through day +100. Allografts included 8/8 HLA-matched related or unrelated donor peripheral blood stem cells. Results: In mice, we show that dual JAK2/mTOR inhibition significantly reduces xenogeneic GVHD and increases peripheral regulatory T cell (Treg) potency as well as Treg induction from conventional CD4+ T cells. Pacritinib 100 mg twice a day was identified as the minimum biologically active and safe dose for further study. JAK2/mTOR inhibition suppresses pathogenic Th1 and Th17 cells, spares Tregs and antileukemia effector cells, and exhibits preliminary activity in preventing GVHD. PAC/SIR/TAC preserves donor cytomegalovirus (CMV) immunity and permits timely engraftment without cytopenias. Conclusions: We demonstrate that PAC/SIR/TAC is safe and preliminarily limits acute GVHD, preserves donor CMV immunity, and permits timely engraftment. The efficacy of PAC/SIR/TAC will be tested in our ongoing phase II GVHD prevention trial.
Algorithm to Evaluate Abnormal Liver Function Tests in Liver Transplant Patients—Reply
Authors: Edward Wolfgang Lee, Sammy Saab, Fady M. Kaldas
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
GD2 redirected CAR T and activated NK-cell-mediated secretion of IFNγ overcomes MYCN-dependent IDO1 inhibition, contributing to neuroblastoma cell immune escape
Authors: Matteo Caforio, Cristina Sorino, Ignazio Caruana, Gerrit Weber, Antonio Camera, Loredana Cifaldi, Biagio De Angelis, Francesca Del Bufalo, Alessia Vitale, Bianca Maria Goffredo, Rita De Vito, Doriana Fruci, Concetta Quintarelli, Maurizio Fanciulli, Franco Locatelli, Valentina Folgiero
Journal: Journal for ImmunoTherapy of Cancer (2021)

Immune escape mechanisms employed by neuroblastoma (NB) cells include secretion of immunosuppressive factors disrupting effective antitumor immunity. The use of cellular therapy to treat solid tumors needs to be implemented. Killing activity of anti-GD2 Chimeric Antigen Receptor (CAR) T or natural killer (NK) cells against target NB cells was assessed through coculture experiments and quantified by FACS analysis. ELISA assay was used to quantify interferon-γ (IFNγ) secreted by NK and CAR T cells. Real Time PCR and Western Blot were performed to analyze gene and protein levels modifications. Transcriptional study was performed by chromatin immunoprecipitation and luciferase reporter assays on experiments of mutagenesis on the promoter sequence. NB tissue sample were analyzed by IHC and Real Time PCR to perform correlation study. We demonstrate that Indoleamine-pyrrole 2,3-dioxygenase1 (IDO1), due to its ability to convert tryptophan into kynurenines, is involved in NB resistance to activity of immune cells. In NB, IDO1 is able to inhibit the anti-tumor effect displayed by of both anti-GD2 CAR (GD2.CAR) T-cell and NK cells, mainly by impairing their IFNγ production. Furthermore, inhibition of MYCN expression in NB results into accumulation of IDO1 and consequently of kynurenines, which negatively affect the immune surveillance. Inverse correlation between IDO1 and MYCN expression has been observed in a wide cohort of NB samples. This finding was supported by the identification of a transcriptional repressive role of MYCN on IDO1 promoter. The evidence of IDO1 involvement in NB immune escape and its ability to impair NK and GD2.CAR T-cell activity contribute to clarify one of the possible mechanisms responsible for the limited efficacy of these immunotherapeutic approaches. A combined therapy of NK or GD2.CAR T-cells with IDO1 inhibitors, a class of compounds already in phase I/II clinical studies, could represent a new and still unexplored strategy capable to improve long-term efficacy of these immunotherapeutic approaches.