Tumour budding, poorly differentiated clusters, and T-cell response in colorectal cancer
| Autor: | David J. Papke, Tomotaka Ugai, Shanshan Shi, Jeffrey A. Meyerhardt, Melissa Zhao, Annacarolina da Silva, Hongmei Nan, Jonathan A. Nowak, Marios Giannakis, Shuji Ogino, Naohiko Akimoto, Tyler S. Twombly, Andrew T. Chan, Xuehong Zhang, Mai Chan Lau, Mingyang Song, Koichiro Haruki, Simeng Gu, Juha P. Väyrynen, Kenji Fujiyoshi, Kota Arima, Jennifer Borowsky, Kana Wu, Jochen K. Lennerz, Junko Kishikawa, Charles S. Fuchs |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Research paper Colorectal cancer epithelial mesenchymal transition lcsh:Medicine PDCs poorly differentiated clusters artificial intelligence clinical outcomes 0302 clinical medicine HPFS Health Professionals Follow-up Study PCR polymerase chain reaction Cytotoxic T cell host-tumour interaction lcsh:R5-920 Tissue microarray ITBCC International Tumour Budding Consensus Conference TNM tumour node and metastases General Medicine MSI microsatellite instability artificial intelligence Prognosis clinical outcomes FFPE formalin-fixed paraffin-embedded CMS consensus molecular subtype 030220 oncology & carcinogenesis AJCC American Joint Committee on Cancer Adenocarcinoma lcsh:Medicine (General) Colorectal Neoplasms Biology EMT epithelial mesenchymal transition PTPRC General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Molecular pathological epidemiology medicine TMA tissue microarray NHS Nurses’ Health Study Humans LINE-1 long-interspersed nucleotide element-1 adenocarcinoma lcsh:R Microsatellite instability IPW inverse probability weighting medicine.disease HR hazard ratio CI confidence interval OR odds ratio 030104 developmental biology molecular pathological epidemiology CIMP CpG island methylator phenotype Cancer research biology.protein SD standard deviation CD8 |
| Zdroj: | EBioMedicine EBioMedicine, Vol 57, Iss, Pp 102860-(2020) |
| ISSN: | 2352-3964 |
| Popis: | Background/Objectives: Tumour budding and poorly differentiated clusters (PDC) represent forms of tumour invasion. We hypothesised that T-cell densities (reflecting adaptive anti-tumour immunity) might be inversely associated with tumour budding and PDC in colorectal carcinoma. Methods: Utilising 915 colon and rectal carcinomas in two U.S.-wide prospective cohort studies, and multiplex immunofluorescence combined with machine learning algorithms, we assessed CD3, CD4, CD8, CD45RO (PTPRC), and FOXP3 co-expression patterns in lymphocytes. Tumour budding and PDC at invasive fronts were quantified by digital pathology and image analysis using the International tumour Budding Consensus Conference criteria. Using covariate data of 4,420 incident colorectal cancer cases, inverse probability weighting (IPW) was integrated with multivariable logistic regression analysis that assessed the association of T-cell subset densities with tumour budding and PDC while adjusting for selection bias due to tissue availability and potential confounders, including microsatellite instability status. Findings: Tumour budding counts were inversely associated with density of CD3+CD8+ [lowest vs. highest: multivariable odds ratio (OR), 0.50; 95% confidence interval (CI), 0.35–0.70; Ptrend < 0.001] and CD3+CD8+CD45RO+ cells (lowest vs. highest: multivariable OR, 0.44; 95% CI, 0.31–0.63; Ptrend < 0.001) in tumour epithelial region. Tumour budding levels were associated with higher colorectal cancer-specific mortality (multivariable hazard ratio, 2.13; 95% CI, 1.57–2.89; Ptrend < 0.001) in Cox regression analysis. There were no significant associations of PDC with T-cell subsets. Interpretation: Tumour epithelial naïve and memory cytotoxic T cell densities are inversely associated with tumour budding at invasive fronts, suggesting that cytotoxic anti-tumour immunity suppresses tumour microinvasion. |
| Databáze: | OpenAIRE |
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