Tumour budding, poorly differentiated clusters, and T-cell response in colorectal cancer

作者: Kenji Fujiyoshi , Juha P. Väyrynen , Jennifer Borowsky , David J. Papke , Kota Arima

DOI: 10.1016/J.EBIOM.2020.102860

关键词: CD8Cytotoxic T cellBiologyColorectal cancerCancer researchTissue microarrayMicrosatellite instabilityMolecular pathological epidemiologyPTPRCAdenocarcinoma

摘要: Abstract Background 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 PDC in colorectal carcinoma. Methods Utilising 915 colon rectal carcinomas two U.S.-wide prospective cohort studies, multiplex immunofluorescence combined machine learning algorithms, we assessed CD3, CD4, CD8, CD45RO (PTPRC), FOXP3 co-expression patterns lymphocytes. at invasive fronts were quantified by digital pathology image analysis using the International Budding Consensus Conference criteria. Using covariate data 4,420 incident cancer cases, inverse probability weighting (IPW) was integrated multivariable logistic regression association subset while adjusting for selection bias due to tissue availability potential confounders, including microsatellite instability status. Findings counts density CD3+CD8+ [lowest vs. highest: odds ratio (OR), 0.50; 95% confidence interval (CI), 0.35–0.70; Ptrend Interpretation epithelial naive memory cytotoxic T cell are fronts, suggesting immunity suppresses microinvasion.

参考文章(63)
Mai Yamauchi, Teppei Morikawa, Aya Kuchiba, Yu Imamura, Zhi Rong Qian, Reiko Nishihara, Xiaoyun Liao, Levi Waldron, Yujin Hoshida, Curtis Huttenhower, Andrew T Chan, Edward Giovannucci, Charles Fuchs, Shuji Ogino, Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum Gut. ,vol. 61, pp. 847- 854 ,(2012) , 10.1136/GUTJNL-2011-300865
Duane H. Hamilton, Bruce Huang, Romaine I. Fernando, Kwong-Yok Tsang, Claudia Palena, WEE1 inhibition alleviates resistance to immune attack of tumor cells undergoing epithelial-mesenchymal transition Cancer Research. ,vol. 74, pp. 2510- 2519 ,(2014) , 10.1158/0008-5472.CAN-13-1894
Natsumi Irahara, Katsuhiko Nosho, Yoshifumi Baba, Kaori Shima, Neal I. Lindeman, Aditi Hazra, Eva S. Schernhammer, David J. Hunter, Charles S. Fuchs, Shuji Ogino, Precision of Pyrosequencing Assay to Measure LINE-1 Methylation in Colon Cancer, Normal Colonic Mucosa, and Peripheral Blood Cells The Journal of Molecular Diagnostics. ,vol. 12, pp. 177- 183 ,(2010) , 10.2353/JMOLDX.2010.090106
Stephen M. Jackson, Natessa Harp, Darshna Patel, Jeffrey Zhang, Savannah Willson, Yoon J. Kim, Christian Clanton, J. Donald Capra, CD45RO enriches for activated, highly mutated human germinal center B cells. Blood. ,vol. 110, pp. 3917- 3925 ,(2007) , 10.1182/BLOOD-2007-05-087767
Reiko Nishihara, Kana Wu, Paul Lochhead, Teppei Morikawa, Xiaoyun Liao, Zhi Rong Qian, Kentaro Inamura, Sun A. Kim, Aya Kuchiba, Mai Yamauchi, Yu Imamura, Walter C. Willett, Bernard A. Rosner, Charles S. Fuchs, Edward Giovannucci, Shuji Ogino, Andrew T. Chan, Long-Term Colorectal-Cancer Incidence and Mortality after Lower Endoscopy The New England Journal of Medicine. ,vol. 369, pp. 1095- 1105 ,(2013) , 10.1056/NEJMOA1301969
Intissar Akalay, Bassam Janji, Meriem Hasmim, Muhammad Zaeem Noman, Fabrice André, Patricia De Cremoux, Philippe Bertheau, Cécile Badoual, Philippe Vielh, Annette K. Larsen, Michèle Sabbah, Tuan Zea Tan, Joan Herr Keira, Nicole Tsang Ying Hung, Jean Paul Thiery, Fathia Mami-Chouaib, Salem Chouaib, Epithelial-to-Mesenchymal Transition and Autophagy Induction in Breast Carcinoma Promote Escape from T-cell–Mediated Lysis Cancer Research. ,vol. 73, pp. 2418- 2427 ,(2013) , 10.1158/0008-5472.CAN-12-2432
Xiaoyun Liao, Paul Lochhead, Reiko Nishihara, Teppei Morikawa, Aya Kuchiba, Mai Yamauchi, Yu Imamura, Zhi Rong Qian, Yoshifumi Baba, Kaori Shima, Ruifang Sun, Katsuhiko Nosho, Jeffrey A. Meyerhardt, Edward Giovannucci, Charles S. Fuchs, Andrew T. Chan, Shuji Ogino, Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. The New England Journal of Medicine. ,vol. 367, pp. 1596- 1606 ,(2012) , 10.1056/NEJMOA1207756
Kentaro Inamura, Mai Yamauchi, Reiko Nishihara, Paul Lochhead, Zhi Rong Qian, Aya Kuchiba, Sun A. Kim, Kosuke Mima, Yasutaka Sukawa, Seungyoun Jung, Xuehong Zhang, Kana Wu, Eunyoung Cho, Andrew T. Chan, Jeffrey A. Meyerhardt, Curtis C. Harris, Charles S. Fuchs, Shuji Ogino, Tumor LINE-1 Methylation Level and Microsatellite Instability in Relation to Colorectal Cancer Prognosis Journal of the National Cancer Institute. ,vol. 106, ,(2014) , 10.1093/JNCI/DJU195