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Article ; Online: TRBC1-targeting antibody-drug conjugates for the treatment of T cell cancers.

Nichakawade, Tushar D / Ge, Jiaxin / Mog, Brian J / Lee, Bum Seok / Pearlman, Alexander H / Hwang, Michael S / DiNapoli, Sarah R / Wyhs, Nicolas / Marcou, Nikita / Glavaris, Stephanie / Konig, Maximilian F / Gabelli, Sandra B / Watson, Evangeline / Sterling, Cole / Wagner-Johnston, Nina / Rozati, Sima / Swinnen, Lode / Fuchs, Ephraim / Pardoll, Drew M /

Gabrielson, Kathy / Papadopoulos, Nickolas / Bettegowda, Chetan / Kinzler, Kenneth W / Zhou, Shibin / Sur, Surojit / Vogelstein, Bert / Paul, Suman

Nature

2024 Volume 628, Issue 8007, Page(s) 416–423

Abstract: Antibody and chimeric antigen receptor (CAR) T cell-mediated targeted therapies have improved ...

Abstract	Antibody and chimeric antigen receptor (CAR) T cell-mediated targeted therapies have improved survival in patients with solid and haematologic malignancies
MeSH term(s)	Animals ; Female ; Humans ; Mice ; Immunoconjugates/immunology ; Immunoconjugates/therapeutic use ; Immunotherapy, Adoptive ; Leukemia, T-Cell/drug therapy ; Leukemia, T-Cell/immunology ; Lymphoma, T-Cell/drug therapy ; Lymphoma, T-Cell/immunology ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; Receptors, Chimeric Antigen/immunology ; T-Lymphocytes/immunology ; Xenograft Model Antitumor Assays
Chemical Substances	Immunoconjugates ; Receptors, Antigen, T-Cell, alpha-beta ; Receptors, Chimeric Antigen ; TRBC1 protein, human
Language	English
Publishing date	2024-03-27
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-024-07233-2
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Zs.A 26: 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: The Role of γδ T-Lymphocytes in Glioblastoma: Current Trends and Future Directions.

Ahmedna, Taha / Khela, Harmon / Weber-Levine, Carly / Azad, Tej D / Jackson, Christopher M / Gabrielson, Kathleen / Bettegowda, Chetan / Rincon-Torroella, Jordina

Cancers

2023 Volume 15, Issue 24

Abstract: ... resistant and immunosuppressive tumor microenvironment (TME). γδ T cells, unconventional T cells expressing ... the characteristic γδ T cell receptor, have demonstrated promise in overcoming these challenges, suggesting great ... immunotherapeutic potential. This review presents the role of γδ T cells in GBM and proposes several research ...

Abstract	Cell-based immunotherapy for glioblastoma (GBM) encounters major challenges due to the infiltration-resistant and immunosuppressive tumor microenvironment (TME). γδ T cells, unconventional T cells expressing the characteristic γδ T cell receptor, have demonstrated promise in overcoming these challenges, suggesting great immunotherapeutic potential. This review presents the role of γδ T cells in GBM and proposes several research avenues for future studies. Using the PubMed, ScienceDirect, and JSTOR databases, we performed a review of the literature studying the biology of γδ T cells and their role in GBM treatment. We identified 15 studies focused on γδ T cells in human GBM. Infiltrative γδ T cells can incite antitumor immune responses in certain TMEs, though rapid tumor progression and TME hypoxia may impact the extent of tumor suppression. In the studies, available findings have shown both the potential for robust antitumor activity and the risk of protumor activity. While γδ T cells have potential as a therapeutic agent against GBM, the technical challenges of extracting, isolating, and expanding γδ T cells, and the activation of antitumoral versus protumoral cascades, remain barriers to their application. Overcoming these limitations may transform γδ T cells into a promising immunotherapy in GBM.
Language	English
Publishing date	2023-12-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15245784
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Article ; Online: Compartmental Analysis of T-cell Clonal Dynamics as a Function of Pathologic Response to Neoadjuvant PD-1 Blockade in Resectable Non-Small Cell Lung Cancer.

Zhang, Jiajia / Ji, Zhicheng / Caushi, Justina X / El Asmar, Margueritta / Anagnostou, Valsamo / Cottrell, Tricia R / Chan, Hok Yee / Suri, Prerna / Guo, Haidan / Merghoub, Taha / Chaft, Jamie E / Reuss, Joshua E / Tam, Ada J / Blosser, Richard L / Abu-Akeel, Mohsen / Sidhom, John-William / Zhao, Ni / Ha, Jinny S / Jones, David R /

Marrone, Kristen A / Naidoo, Jarushka / Gabrielson, Edward / Taube, Janis M / Velculescu, Victor E / Brahmer, Julie R / Housseau, Franck / Hellmann, Matthew D / Forde, Patrick M / Pardoll, Drew M / Ji, Hongkai / Smith, Kellie N

Clinical cancer research : an official journal of the American Association for Cancer Research

2019 Volume 26, Issue 6, Page(s) 1327–1337

Abstract: ... we explored whether the peripheral T-cell clonotypic dynamics can serve as a biomarker for response ... to neoadjuvant PD-1 blockade.: Experimental design: T-cell receptor (TCR) sequencing was performed on serial ... blockade. We explored the temporal dynamics of the T-cell repertoire in the peripheral and tumoral ...

Abstract	Purpose: Neoadjuvant PD-1 blockade is a promising treatment for resectable non-small cell lung cancer (NSCLC), yet immunologic mechanisms contributing to tumor regression and biomarkers of response are unknown. Using paired tumor/blood samples from a phase II clinical trial (NCT02259621), we explored whether the peripheral T-cell clonotypic dynamics can serve as a biomarker for response to neoadjuvant PD-1 blockade. Experimental design: T-cell receptor (TCR) sequencing was performed on serial peripheral blood, tumor, and normal lung samples from resectable NSCLC patients treated with neoadjuvant PD-1 blockade. We explored the temporal dynamics of the T-cell repertoire in the peripheral and tumoral compartments in response to neoadjuvant PD-1 blockade by using the TCR as a molecular barcode. Results: Higher intratumoral TCR clonality was associated with reduced percent residual tumor at the time of surgery, and the TCR repertoire of tumors with major pathologic response (MPR; <10% residual tumor after neoadjuvant therapy) had a higher clonality and greater sharing of tumor-infiltrating clonotypes with the peripheral blood relative to tumors without MPR. Additionally, the posttreatment tumor bed of patients with MPR was enriched with T-cell clones that had peripherally expanded between weeks 2 and 4 after anti-PD-1 initiation and the intratumoral space occupied by these clonotypes was inversely correlated with percent residual tumor. Conclusions: Our study suggests that exchange of T-cell clones between tumor and blood represents a key correlate of pathologic response to neoadjuvant immunotherapy and shows that the periphery may be a previously underappreciated originating compartment for effective antitumor immunity.
MeSH term(s)	Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Neoadjuvant Therapy ; Programmed Cell Death 1 Receptor ; T-Lymphocytes
Chemical Substances	Programmed Cell Death 1 Receptor
Language	English
Publishing date	2019-11-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-19-2931
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Zs.A 4223: Show issues

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Article ; Online: Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC.

Cancer immunology research

2016 Volume 4, Issue 5, Page(s) 419–430

Abstract: ... CD8(+)) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage ... of both CD3(+) and CD8(+) T cells in both the interior and margin, along with corresponding Immunoscores, were ...

Abstract	Immune cells that infiltrate a tumor may be a prognostic factor for patients who have had surgically resected hepatocellular carcinoma (HCC). The density of intratumoral total (CD3(+)) and cytotoxic (CD8(+)) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage I to IV HCC tissue specimens from a single cohort. Immune cell density in the interior and margin was converted to a binary score (0, low; 1, high), which was correlated with tumor recurrence and relapse-free survival (RFS). In addition, the expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) was correlated with the density of CD3(+) and CD8(+) cells and clinical outcome. High densities of both CD3(+) and CD8(+) T cells in both the interior and margin, along with corresponding Immunoscores, were significantly associated with a low rate of recurrence (P = 0.007) and a prolonged RFS (P = 0.002). In multivariate logistic regression models adjusted for vascular invasion and cellular differentiation, both CD3(+) and CD8(+) cell densities predicted recurrence, with odds ratios of 5.8 [95% confidence interval (CI), 1.6-21.8] for CD3(+) and 3.9 (95% CI, 1.1-14.1) for CD8(+) Positive PD-L1 staining was correlated with high CD3 and CD8 density (P = 0.024 and 0.005, respectively) and predicted a lower rate of recurrence (P = 0.034), as well as prolonged RFS (P = 0.029). Immunoscore and PD-L1 expression, therefore, are useful prognostic markers in patients with HCC who have undergone primary tumor resection. Cancer Immunol Res; 4(5); 419-30. ©2016 AACR.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; B7-H1 Antigen/metabolism ; Biomarkers, Tumor/metabolism ; CD3 Complex/metabolism ; CD8-Positive T-Lymphocytes/immunology ; Carcinoma, Hepatocellular/diagnosis ; Carcinoma, Hepatocellular/immunology ; Carcinoma, Hepatocellular/pathology ; Carcinoma, Hepatocellular/surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/diagnosis ; Liver Neoplasms/immunology ; Liver Neoplasms/pathology ; Liver Neoplasms/surgery ; Lymphocytes, Tumor-Infiltrating/immunology ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Proteins/metabolism ; Neoplasm Staging ; Prognosis ; Recurrence ; Risk Factors ; T-Lymphocyte Subsets/immunology
Chemical Substances	B7-H1 Antigen ; Biomarkers, Tumor ; CD274 protein, human ; CD3 Complex ; Neoplasm Proteins
Language	English
Publishing date	2016-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2732489-8
ISSN	2326-6074 ; 2326-6066
ISSN (online)	2326-6074
ISSN	2326-6066
DOI	10.1158/2326-6066.CIR-15-0110
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Zs.A 7022: Show issues

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Article ; Online: T-cell epitope content comparison (EpiCC) of swine H1 influenza A virus hemagglutinin.

Gutiérrez, Andres H / Rapp-Gabrielson, Vicki J / Terry, Frances E / Loving, Crystal L / Moise, Leonard / Martin, William D / De Groot, Anne S

Influenza and other respiratory viruses

2017 Volume 11, Issue 6, Page(s) 531–542

Abstract: ... in human and animal vaccine design. T-cell epitope cross-conservation may play an important role in cross ... correlate of protection has been identified for T-cell epitopes.: Objective: We developed a computational ... property-T-cell epitope content-rather than sequence identity, and evaluated its ability to classify swine ...

Abstract	Background: Predicting vaccine efficacy against emerging pathogen strains is a significant problem in human and animal vaccine design. T-cell epitope cross-conservation may play an important role in cross-strain vaccine efficacy. While influenza A virus (IAV) hemagglutination inhibition (HI) antibody titers are widely used to predict protective efficacy of 1 IAV vaccine against new strains, no similar correlate of protection has been identified for T-cell epitopes. Objective: We developed a computational method (EpiCC) that facilitates pairwise comparison of protein sequences based on an immunological property-T-cell epitope content-rather than sequence identity, and evaluated its ability to classify swine IAV strain relatedness to estimate cross-protective potential of a vaccine strain for circulating viruses. Methods: T-cell epitope relatedness scores were assessed for 23 IAV HA sequences representing the major H1 swine IAV phylo-clusters circulating in North American swine and HA sequences in a commercial inactivated vaccine (FluSure XP Results: Higher EpiCC scores were associated with greater protection by the vaccine against strains for 23 field IAV strain vaccine comparisons. A threshold for EpiCC relatedness associated with full or partial protection in the absence of cross-reactive HI antibodies was identified. EpiCC scores for field strains for which FluSure protective efficacy is not yet available were also calculated. Conclusion: EpiCC thresholds can be evaluated for predictive accuracy of protection in future efficacy studies. EpiCC may also complement HI cross-reactivity and phylogeny for selection of influenza strains in vaccine development.
MeSH term(s)	Algorithms ; Animals ; Computers, Molecular ; Cross Protection/genetics ; Cross Protection/immunology ; Epitope Mapping/methods ; Epitopes, T-Lymphocyte/chemistry ; Epitopes, T-Lymphocyte/genetics ; Epitopes, T-Lymphocyte/immunology ; Hemagglutinins/chemistry ; Hemagglutinins/genetics ; Hemagglutinins/immunology ; Histocompatibility Antigens Class I/immunology ; Influenza A virus/chemistry ; Influenza A virus/immunology ; Orthomyxoviridae Infections/virology ; Sequence Analysis, Protein/methods ; Swine ; Swine Diseases/virology ; Vaccine Potency
Chemical Substances	Epitopes, T-Lymphocyte ; Hemagglutinins ; Histocompatibility Antigens Class I ; swine leukocyte antigen
Language	English
Publishing date	2017-10-09
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2274538-5
ISSN	1750-2659 ; 1750-2640
ISSN (online)	1750-2659
ISSN	1750-2640
DOI	10.1111/irv.12513
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Zs.A 6568: Show issues

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Article ; Online: EDITORIAL COMMENT.

Choi, Una / Gabrielson, Andrew T

Urology

2023 Volume 173, Page(s) 117

Language	English
Publishing date	2023-03-23
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	192062-5
ISSN	1527-9995 ; 0090-4295
ISSN (online)	1527-9995
ISSN	0090-4295
DOI	10.1016/j.urology.2022.11.045
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Zs.A 1142: 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: Medical School Rankings: Time to End or Time to Amend?

Gabrielson, Andrew T / Ziegelstein, Roy C

Academic medicine : journal of the Association of American Medical Colleges

2023 Volume 99, Issue 3, Page(s) 247–250

Abstract: Abstract: The recent decisions of several medical schools to no longer participate in the rankings published annually by U.S. News & World Report have added greater visibility to the issues surrounding medical school rankings than ever before. While ... ...

Abstract	Abstract: The recent decisions of several medical schools to no longer participate in the rankings published annually by U.S. News & World Report have added greater visibility to the issues surrounding medical school rankings than ever before. While these announcements garnered significant attention in academic medicine and from the lay public, the authors believe these events are unlikely to eliminate rankings in medical education. In this article, the authors outline the potential harms of rankings in higher education, provide a rationale for why they will likely endure despite recent scrutiny, and offer suggestions for prospective students and the academic medical community to engage with rankings in a more productive way. Criticisms of medical school rankings have been noted for decades, including their use of subjective information and data with questionable relevance to the quality of students' education or the outcomes of their educational experience, methodological concerns, and the potential harms of ranking systems (such as schools diverting their focus and resources away from initiatives that benefit students to improve their ranking). At the same time, rankings are ubiquitous in today's culture and are powerful in human decision-making, so there is reason to believe that medical school rankings may weather the current storm. Given these concerns, the authors suggest students continue to use a variety of resources to obtain information about medical schools and consider how each school fits with their own educational needs. The authors also encourage medical schools, medical education organizations, and governing medical bodies to suggest different metrics that reflect quality in medical education and that are of importance to applicants.
MeSH term(s)	Humans ; Schools, Medical ; Students ; Education, Medical ; Research Report
Language	English
Publishing date	2023-11-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	96192-9
ISSN	1938-808X ; 1040-2446
ISSN (online)	1938-808X
ISSN	1040-2446
DOI	10.1097/ACM.0000000000005566
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Zs.A 112: Show issues

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Article ; Online: Assessment of musculoskeletal pain and surgical ergonomic parameters among members of the American Society of Pediatric Otolaryngology.

Gabrielson, Andrew T / Wei, Julie

International journal of pediatric otorhinolaryngology

2023 Volume 176, Page(s) 111765

Abstract: Objectives: To assess rates of self-reported work-related pain and knowledge of ergonomic principles among fellowship trained pediatric otolaryngologists within the American Society of Pediatric Otolaryngology (ASPO). We hypothesized that pediatric ... ...

Abstract	Objectives: To assess rates of self-reported work-related pain and knowledge of ergonomic principles among fellowship trained pediatric otolaryngologists within the American Society of Pediatric Otolaryngology (ASPO). We hypothesized that pediatric otolaryngologists experience rates of musculoskeletal pain and injury similar to what has been reported among adult otolaryngologists and other surgical subspecialties. Methods: An IRB-approved survey was distributed to members of ASPO through email listserv. Collected variables included surgeon demographic information, practice settings, surgical volume, procedure types, work-related musculoskeletal pain-related metrics, modifying factors, and knowledge/attitudes on surgical ergonomics. Results: A total of 685 ASPO members were approached via email, of which 435 opened the survey email and 118 attending pediatric otolaryngologists completed the survey (response rate 27%). In all, 78% of respondents reported current or prior pain and/or injury attributed to performing surgery, 20% higher than that reported in the previous ergonomics survey of ASPO members in 2012. The most affected areas were neck/cervical spine (63%), shoulders/arms (44%), lower back/lumbar spine (36%), and hands/wrist (31%). Half of the respondents were diagnosed with musculoskeletal condition(s) attributed to performing surgery. Two-thirds required treatment (62% pharmacologic only, 9% pharmacologic and surgical intervention) for their work-related pain. Leveraging intermittent pauses during surgical procedures to adjust body position was the most reported method of addressing pain in the operating room. Only 21% report ever having received ergonomic training during their training or career. Conclusion: Musculoskeletal pain associated with performing pediatric otolaryngology procedures is highly prevalent and has not attenuated despite increased awareness of surgical ergonomics. Results from this study underscore the need to develop standardized surgical ergonomics curricula for pediatric otolaryngologists and trainees.
MeSH term(s)	Adult ; Humans ; United States ; Child ; Musculoskeletal Pain/diagnosis ; Otolaryngology ; Otolaryngologists ; Surveys and Questionnaires ; Ergonomics
Language	English
Publishing date	2023-11-07
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	754501-0
ISSN	1872-8464 ; 0165-5876
ISSN (online)	1872-8464
ISSN	0165-5876
DOI	10.1016/j.ijporl.2023.111765
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Zs.A 1507: 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)
Zs.MO 134: Show issues

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Article ; Online: The case for improved transparency of disability insurance and workers' compensation claims data to study work-related injuries among surgeons.

Gabrielson, Andrew T / Corwin, Claudia / Chrouser, Kristin

American journal of surgery

2024

Language	English
Publishing date	2024-04-02
Publishing country	United States
Document type	Editorial
ZDB-ID	2953-1
ISSN	1879-1883 ; 0002-9610
ISSN (online)	1879-1883
ISSN	0002-9610
DOI	10.1016/j.amjsurg.2024.03.025
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Article ; Online: Critically Evaluating the Role for Postoperative Antibiotics in Patients Undergoing Urethroplasty with Buccal Mucosa Graft: A Claims Database Analysis.

Galansky, Logan / Gabrielson, Andrew T / Cohen, Andrew J

Urology

2024

Abstract: Objectives: To compare outcomes among patients undergoing first-time urethroplasty with buccal mucosa graft (BMG) who receive post-operative antibiotics versus those who do not.: Methods: A retrospective cohort study was conducted using the TriNetX ... ...

Abstract	Objectives: To compare outcomes among patients undergoing first-time urethroplasty with buccal mucosa graft (BMG) who receive post-operative antibiotics versus those who do not. Methods: A retrospective cohort study was conducted using the TriNetX claims database between 2008-2022. Using CPT, ICD10, and LOINC codes, patients >18 years old undergoing primary urethroplasty with BMG who received an outpatient prescription for antibiotics between post-operative day 0-30 or did not were queried. Patients with positive pre-operative urine culture or urinary tract infection (UTI) within 30 days pre-operatively were excluded. Surgical outcomes included 5-year revision rates and revision-free survival. Safety outcomes included new UTI within 30 days, surgical site infection (SSI) within 90 days, or Clostridium difficile infection within 30 days of urethroplasty. Results: We identified 884 patients (81% antibiotic cohort, 19% non-antibiotic cohort) that met inclusion criteria. Age at time of urethroplasty, suprapubic tube presence, and pre-existing medical comorbidities were comparable between cohorts (Table 1A). There was no difference in 5-year rates and revision-free survival for endoscopic revision (11.5% vs. 9.5%, RR 1.2, 95% CI [0.7, 2.0], RFS log-rank p=0.6), re-do urethroplasty (12.9% vs. 13.7%, RR 0.9, 95% CI [0.6, 1.5], RFS log-rank p=0.7), or all-cause revision (19.8% vs. 17.7%, RR 1.1, 95% CI [0.8, 1.6], p=0.5) between groups. Post-operative rates of UTI, SSI, and Clostridium difficile infection were similar between groups. Conclusions: In this large retrospective cohort study of patients undergoing urethroplasty with BMG, we observed no significant benefit from use of post-operative antibiotics on long-term revision rates or perioperative infectious complications.
Language	English
Publishing date	2024-04-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	192062-5
ISSN	1527-9995 ; 0090-4295
ISSN (online)	1527-9995
ISSN	0090-4295
DOI	10.1016/j.urology.2024.03.036
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