Sökning: onr:"swepub:oai:DiVA.org:uu-517163" > Improving the diagn...
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000 | 04969nam a2200481 4500 | |
001 | oai:DiVA.org:uu-517163 | |
003 | SwePub | |
008 | 231204s2024 | |||||||||||000 ||eng| | |
020 | a 9789151319841q print | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5171632 URI |
040 | a (SwePub)uu | |
041 | a engb engb -1 | |
042 | 9 SwePub | |
072 | 7 | a vet2 swepub-contenttype |
072 | 7 | a dok2 swepub-publicationtype |
100 | 1 | a Elfving, Hedvigu Uppsala universitet,Institutionen för immunologi, genetik och patologi4 aut0 (Swepub:uu)hedel331 |
245 | 1 0 | a Improving the diagnostic armamentarium of lung cancer |
264 | 1 | a Uppsala :b Acta Universitatis Upsaliensis,c 2024 |
300 | a 48 s. | |
338 | a electronic2 rdacarrier | |
490 | 0 | a Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine,x 1651-6206 ;v 2000 |
520 | a Lung cancer is the leading cause of cancer-related death globally, with non-small cell lung cancer (NSCLC) constituting 85% of cases. The introduction of immunotherapies and targeted therapies have dramatically improved the prognosis and outcome for a subset of patients, and stressed the development of diagnostic tools for effective patient selection. This thesis addresses different aspects of current and future diagnostic strategies in NSCLC patients.In Paper I, an immunohistochemical assay targeting the neurotropic tropomyosin receptor kinase (NTRK) was evaluated on tissue microarrays (TMAs) from a well-characterized NSCLC cohort. Although a few cases showed positive staining, none were positive in the reference molecular testing, highlighting the rarity of this targetable aberration and underscoring the value of cost-effective screening methods.In Paper II, paired patient samples (biopsy, TMA, and surgical specimen) were evaluated regarding the immunohistochemical staining for PD-L1. The results indicated a strong correlation between the PD-L1 expression on biopsy and TMA compared with the tumor whole slide, suggesting that tumor heterogeneity has minor relevance for PD-L1 evaluation.In Paper III, paired tissue samples (biopsy, TMA, and surgical specimen) were evaluated regarding infiltrating CD3+ immune cells. Only weak correlation was found between the biopsies and tumor whole slide, while the agreement between the whole slide and TMA was higher. These results question the use of biopsies for immune cell quantification, while supporting the TMA as a reliable tool in cancer research.In Paper IV, the amount and distribution of tertiary lymphoid structures (TLS) was annotated on scanned tumor whole slides. TLS were present in most of the tumors and correlated with the abundance of specific immune cell subsets. Higher number of TLS were associated with longer survival, particularly in adenocarcinomas. High tumor mutational burden was associated with higher numbers of periphery TLS. These results provide a rationale for using TLS metrics as a diagnostic marker for NSCLC patients undergoing surgical resection.In summary, this thesis addresses challenges in prognostic and predictive lung cancer diagnostics in the areas of targeted therapy and immunotherapy. The results provide crucial insights into tumor heterogeneity that may impact clinical decision-making and aid scientists in selecting appropriate tissue sources for translational and clinical cancer research. | |
520 | a | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng |
653 | a lung cancer | |
653 | a tissue microarray | |
653 | a immunohistochemistry | |
653 | a targeted therapy | |
653 | a immunotherapy | |
653 | a checkpoint inhibitors | |
653 | a immune microenvironment | |
653 | a prognosis | |
653 | a biomarkers | |
653 | a immune cells. | |
700 | 1 | a Micke, Patrick,c Professoru Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi,Cancerimmunterapi4 ths0 (Swepub:uu)patmi676 |
700 | 1 | a Pontén, Fredrik,c Professoru Uppsala universitet,Science for Life Laboratory, SciLifeLab,Cancerprecisionsmedicin4 ths0 (Swepub:uu)fredpont |
700 | 1 | a Nestor, Marika,d 1976-u Uppsala universitet,Öron-, näs- och halssjukdomar,Science for Life Laboratory, SciLifeLab,Cancerprecisionsmedicin4 ths0 (Swepub:uu)manes424 |
700 | 1 | a Büttner, Reinhard,c Professoru Institute of Pathology, University of Cologne, Germany4 opn |
710 | 2 | a Uppsala universitetb Institutionen för immunologi, genetik och patologi4 org |
856 | 4 | u https://uu.diva-portal.org/smash/get/diva2:1816906/FULLTEXT01.pdfx primaryx Raw objecty fulltext |
856 | 4 | u https://uu.diva-portal.org/smash/get/diva2:1816906/PREVIEW01.jpgx Previewy preview image |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-517163 |
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