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doctoral thesis
Cytotoxic and immunosuppressive inflammatory cells predict regression and prognosis following neoadjuvant radio chemotherapy of esophageal adenocarcinoma
2023. urn:nbn:hr:171:883713
Göbel, Holger
University of Split
School of Medicine

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Göbel, H. (2023). Cytotoxic and immunosuppressive inflammatory cells predict regression and prognosis following neoadjuvant radio chemotherapy of esophageal adenocarcinoma (Doctoral thesis). Split: University of Split, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:171:883713

Göbel, Holger. "Cytotoxic and immunosuppressive inflammatory cells predict regression and prognosis following neoadjuvant radio chemotherapy of esophageal adenocarcinoma." Doctoral thesis, University of Split, School of Medicine, 2023. https://urn.nsk.hr/urn:nbn:hr:171:883713

Göbel, Holger. "Cytotoxic and immunosuppressive inflammatory cells predict regression and prognosis following neoadjuvant radio chemotherapy of esophageal adenocarcinoma." Doctoral thesis, University of Split, School of Medicine, 2023. https://urn.nsk.hr/urn:nbn:hr:171:883713

Göbel, H. (2023). 'Cytotoxic and immunosuppressive inflammatory cells predict regression and prognosis following neoadjuvant radio chemotherapy of esophageal adenocarcinoma', Doctoral thesis, University of Split, School of Medicine, accessed 13 April 2025, https://urn.nsk.hr/urn:nbn:hr:171:883713

Göbel H. Cytotoxic and immunosuppressive inflammatory cells predict regression and prognosis following neoadjuvant radio chemotherapy of esophageal adenocarcinoma [Doctoral thesis]. Split: University of Split, School of Medicine; 2023 [cited 2025 April 13] Available at: https://urn.nsk.hr/urn:nbn:hr:171:883713

H. Göbel, "Cytotoxic and immunosuppressive inflammatory cells predict regression and prognosis following neoadjuvant radio chemotherapy of esophageal adenocarcinoma", Doctoral thesis, University of Split, School of Medicine, Split, 2023. Available at: https://urn.nsk.hr/urn:nbn:hr:171:883713

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Metadata
TitleCytotoxic and immunosuppressive inflammatory cells predict regression and prognosis following neoadjuvant radio chemotherapy of esophageal adenocarcinoma
Title (croatian)Citotoksične i imunosupresivne upalne stanice predviđaju regresiju i prognozu nakon neoadjuvantne radiokemoterapije adenokarcinoma jednjaka
AuthorHolger Göbel https://orcid.org/0000-0002-9645-0414
MentorGeorg Gerhard Grabenbauer (mentor)
MentorThomas Aigner https://orcid.org/0000-0001-5445-5893 (mentor)
Committee memberEduard Vrdoljak (predsjednik povjerenstva)
Committee memberAntonio Juretić (član povjerenstva)
Committee memberSnježana Tomić (član povjerenstva)
GranterUniversity of Split
School of Medicine
Split
Defense date and country2023-12-14, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Oncology
Universal decimal classification
(UDC)		616 - Pathology. Clinical medicine
Abstract
Background and purpose: Tumour infiltrating lymphocytes (TIL), tumour associated macrophages (TAM) and PD-L1/PD-1 expression play a key role in anticancer immunosurveillance. We studied their influence on response to neoadjuvant radiochemotherapy (RCT) and prognosis in patients with oesophageal adenocarcinoma (OAC). Materials and methods: Between 10/2004 and 06/2018, pre-RCT biopsy-specimens were available from 76 patients with locally advanced, non-metastatic OAC scheduled for trimodality therapy. We evaluated intra- and peritumoural expression of FoxP3+, CD8+, CD68+, CD163+, and PD-L1/PD-1 to determine their influence on tumour regression grade (TRG) and survival. Results: Poor tumour regression was detected for cN+ (RR 0.77 [95% CI 0.66-0.90], p=0.001), low intratumoural FoxP3+/CD8+ ratio (RR 0.75 [0.60-0.96], p=0.020), high peritumoural CD163+/CD68+ ratio (RR 0.77 [0.60-0.99], p=0.045), high intratumoural TAM density (RD - 0.44 [-0.82 to -0.06], p=0.023), and negative peritumoural PD-L1 expression (RR 0.75 [0.57- 0.98], p=0.036). Apart from poor resection quality and TRG, pretherapeutic high peritumoural CD8+ infiltration (HR 2.36 [1.21-4.61], p=0.012), short intratumoural FoxP3+ to CD8+ cell-to-cell distances in middle ranged CD8+ density (HR 2.55 [1.00-6.52], p=0.050), positive intratumoural PD-1 expression (HR 1.92 [1.08-3.45], p=0.038), and low intratumoural CD8+ density combined with positive PD-L1 expression (HR 3.13 [1.12-8.33], p=0.042) were significant unfavourable prognostic factors in multivariate analysis. Conclusions: The evaluated immunologic parameters showed independent predictive and prognostic value in patients with OAC.
Abstract (croatian)
Pozadina i svrha: Tumor infiltrišući limfociti (TIL), tumor asocirani makrofagi (TAM) i PDL1/PD-1 ekspresija igra ključnu ulogu u antikancerskom imunološkom nadzoru. Mi smo proučavali njihov uticaj na odgovor na neoadjuvantnu radiohemoterapiju (RCT) i prognozu kod pacijenata sa adenokarcinomima ezofagusa (OAC). Materijali i metode: Između 10/2004 i 06/2018, uradjena je pre-RCT biopsija-uzoraka od ukupno 76 pacijenata sa lokalno uznapredovalim, ne metastatskim OAC pripremanih za trimodalnu terapiju. Procenjivali smo intra- i peritumoralnu ekspresiju FoxP3+, CD8+, CD68+, CD163+ i PD-L1/PD-1 da bi utvrdili njihov uticaj na stepen tumorske regresije (TRG) i preživljavanje. Rezultati: Slaba tumorska regresija je uočena kod cN+ (RR 0.77 [95% CI 0.66-0.90], p=0.001), nizak intratumorski FoxP3+/CD8+ racio (RR 0.75 [0.60-0.96], p=0.020), visok peritumorski CD163+/CD68+ racio (RR 0.77 [0.60-0.99], p=0.045), visoka intratumorska gustina TAM (RD -0.44 [-0.82 to -0.06], p=0.023), i negativna peritumorska PD-L1 ekspresija (RR 0.75 [0.57- 0.98], p=0.036). Nezavisno od slabog resekcionog kvaliteta i TRG, preterapijska visoka peritumoralna CD8+ infiltracija (HR 2.36 [1.21-4.61], p=0.012), kratke intratumorske FoxP3+ do CD8+ udaljenosti ćelije od ćelije kod srednje CD8+ intratumorske gustine (HR 2.55 [1.00-6.52], p=0.050), pozitivna intratumorska PD-1 ekspresija (HR 1.92 [1.08-3.45], p=0.038), i niska intratumorska CD8+ gustina u kombinacija sa pozitivnom PD-L1 ekspresijom (HR 3.13 [1.12-8.33], p=0.042) bili su značajno nepovoljni prognostički faktori u multivarijantnoj analizi. Zaključci: Procenjivani imunološki parametri pokazali su nezavisnu prediktivnu i prognostičku vrednost kod pacijenata sa adenokarcinomima ezofagusa.
Keywords
Keywords (croatian)
Languageenglish
URN:NBNurn:nbn:hr:171:883713
Promotion2023
Study programmeTitle: Evidence-Based Clinical Medicine
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2023-12-07 14:13:29