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| 1 | Cytotoxic CD8+ T cells and tissue resident memory cells in colorectal cancer based on microsatellite instability and BRAF status显示文摘BACKGROUND Recent studies in non-colorectal malignancy have associated T resident memory(T_(RM)) cells with improved patient survival. It is unknown if T_(RM) plays a role in colorectal cancer(CRC).AIM To examine the potential role of T_(RM) cells in providing immunogenicity in CRC stratified by microsatellite instability(MSI) and BRAF status.METHODS Patients with known MSI and BRAF mutation status were eligible for inclusion in this study. CRC tumour sections stained with haematoxylin and eosin were microscopically reviewed and the images scanned prior to assessment for location of invading edge and core of tumour. Sequential sections were prepared for quantitative multiplex immunohistochemistry(IHC) staining. Opal Multiplex IHC staining was performed with appropriate positive and negative controls and imaged using a standard fluorescent microscope fitted with a spectral scanning camera(Mantra) in conjunction with Mantra snap software. Images were unmixed and annotated in in Form 2.2.0. Statistical analysis was performed using Graphpad Prism Version 7 and Stata Version 15.RESULTS Seventy-two patients with known MSI and BRAF status were included in the study. All patients were assessed for MSI by IHC and high resolution capillary electrophoresis testing and 44 of these patients successfully underwent quantitative multiplex IHC staining. Overall, there was a statistically significant increase in CD8+ T_(RM) cells in the MSI(BRAF mutant and wild type) group over the microsatellite stable(MSS) group. There was a statistically significant difference in CD8+ T_(RM) between high level MSI(MSI-H):BRAF mutant [22.57, 95% confidence interval(CI): 14.31-30.84] vs MSS [8.031(95%CI: 4.698-11.36)], P = 0.0076 and MSI-H:BRAF wild type [16.18(95%CI: 10.44-21.93)] vs MSS [8.031(95%CI: 4.698-11.36)], P = 0.0279. There was no statistically significant difference in CD8 T cells(both CD8+CD103-and CD8+CD103+T_(RM)) between MSI-H: BRAF mutant and wild type CRC.CONCLUSION This study has shown that CD8+ T_(RM) are found in greater abundance in MSI-H CRC, both BRAF mutant and MSI-H:BRAF wild type, when compared with their MSS counterpart. CD8+ T_(RM) may play a role in the immunogenicity in MSI-H CRC(BRAF mutant and BRAF wild type). Further studies should focus on the potential immunogenic qualities of T_(RM) cells and investigate potential immunotherapeutic approaches to improve treatment and survival associated with CRC. | James Wei Tatt Toh Angela L Ferguson Kevin J Spring Hema Mahajan Umaimainthan Palendira | 2021 | World Journal of Clinical Oncology2021，12，4： | 2 |
| 2 | Colorectal carcinogenesis:Road maps to cancer显示文摘 | Daniel L Worthley Vicki L Whitehall Kevin J Spring Barbara A Leggett | 2007 | World Journal of Gastroenterology2007，，28： | 2 |
| 3 | Comribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis显示文摘 | Willams DL Spring K Collins L | 1998 | Antimicrob Agents Chemother1998，42，： | 1 |
| 4 | Perfusion CT best predicts outcome after radioembolization of liver metasta- ses: a comparison of radionuclide and CT imaging techniques 显示文摘 | MORSBACH F SAH B R SPRING L | 2014 | EurRadiol2014，24，7： | 1 |
| 5 | Services, products, and the institutional structure of production 显示文摘 | Araujo L M Spring M | 2006 | Industrial Mark- ring Management2006，35，7： | 1 |
| 6 | Optimized control of a pressure-wave supercharger: a model-based feedforward approach 显示文摘 | SPRING P ONDER C H GUZZELLA L | 2007 | IEEE Transactions on Control Systems Technology2007，15，3： | 1 |
| 7 | Report from the international atomic energy agency (IAEA) consultants' meeting on elective nodal irradiation in lung cancer:non-small-cell lung cancer (NSCLC)显示文摘 | Belderbos JS Kepka L Spring KF | | 0，，： | 1 |
| 8 | A New Measure of Process Capability Cpm 显示文摘 | S W Cheng F A Spring | 1988 | Journal of Quality Technology1988，20，3： | 1 |
| 9 | Services, Products, and the Institutional Structure of Production显示文摘 | Araujo L Spring M | | 0，，07： | 1 |
| 10 | EGR control of pressure- wave supercharged IC engines 显示文摘 | Spring P Onder C H Guzzella L | 2007 | Control Engineering Practice2007，15，12： | 1 |
| 11 | A new measure of progress capability index显示文摘 | Chan L K Cheng S W Spring F A | 1988 | Journal of Quality Technology1988，20，3： | 1 |
| 12 | Effects of marman oligosaccharide (MOS) supplementation on growth performance, feed utilisation, intestinal histology and gut microbiota of gilthead sea bream (Sparus aurata) 显示文摘 | Dimitroglou A Merrifield D L Spring P | 2010 | Aqua- culture2010，300，14： | 1 |
| 13 | Genome sequence of the Thermotoga thermarum type strain (LA3T) from an African solfataric spring 显示文摘 | G?ker M Spring?S Scheuner C Anderson I Zeytun A Nolan M Lucas S Tice H Del Rio TG Cheng JF Han C Tapia R Goodwin LA Pitluck S Liolios K Mavromatis K Pagani I Ivanova N Mikhailova N Pati A Chen A Palaniappan K Land M Hauser L Chang YJ Jeffries CD Rohde M Detter JC Woyke T Bristow J Eisen JA Markowitz V Hugenholtz P Kyrpides NC Klenk HP Lapidus A | 2014 | Stand Genomic Sci2014，9，3： | 1 |
| 14 | Dietary man- nan oligosaccharide supplementation modulates intestinal microbial ecology and improves gut morphology of rainbow trout, Oncorhynchus mykiss 显示文摘 | Dimitroglou A Merrifield D L Spring P | 2009 | N Am J Aquacult2009，87，： | 1 |
| 15 | Histoligical and biochemcal criteria for objective and early selection of grapexine cultivars resistant to plasmopara viticola显示文摘 | Gindro K Spring J L Pezet R et ol | 2006 | Vitis2006，45，4： | 1 |
| 16 | A new measure of process capability index Cpm 显示文摘 | Chan L K Cheng S W Spring F A | 1988 | Journal of Quality Technology1988，20，3： | 1 |
| 17 | Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis 显示文摘 | Williams DL Spring L Collins L | 1998 | Antimicrob Agents Chemother1998，42，7： | 1 |
| 18 | Galectin 1 is involved in vascular smooth muscle cell proliferation 显示文摘 | Moiseeva E P Javed Q Spring E L | 2000 | Cardiovasc Res2000，45，2： | 1 |
| 19 | Effects of mannan oligosaccharide (MOS) sup-plementation on growth performance,feed utilisation,intestinal histology and gut microbiota of gilthead seabream (Sparus aurata) 显示文摘 | DIMITROGLOU A MERRIFIELD D L SPRING P | 2010 | Aquaculture2010，300，： | 1 |
| 20 | A new measure of process capability index Cpm 显示文摘 | Chan L K Cheng S W Spring F A | 1988 | Journal of Quality Technology1988，20，3： | 1 |
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