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Cytotoxic CD8+ T cells and tissue resident memory cells in colorectal cancer based on microsatellite instability and BRAF status

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World Journal of Clinical Oncology 2021年第4期12卷 238-248页

作者： James Wei Tatt Toh Angela L Ferguson Kevin J Spring Hema Mahajan Umaimainthan Palendira Division of Surgery and Anaesthesia Department of Colorectal SurgeryWestmead HospitalWestmead Clinical SchoolThe University of SydneyIngham Institute for Applied Medical ResearchWestmead 2145NSWAustralia Department of Infectious Diseases and Immunology School of Medical SciencesFaculty of Medicine and HealthHuman Viral&Cancer ImmunologyCentenary InstituteCharles Perkin CentreThe University of SydneySydney 2000NSWAustralia Medical Oncology Group Ingham Institute for Applied Medical ResearchLiverpool HospitalLiverpool Clinical SchoolUniversity of Western SydneySouth Western Clinical School UNSWLiverpool 2170NSWAustralia Department of Anatomical Pathology ICPMRWestmead HospitalWestmead 2145NSWAustralia Department of Immunology and Infectious Diseases School of Medical SciencesFaculty of Medicine and HealthThe University of SydneySydney 2000NSWAustralia

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 *** 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 *** 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 *** This study has

关键词： tissue resident memory cells resident memory T cells Colorectal cancer Microsatellite instability BRAF DNA mismatch repair Immunotherapy Prognosis

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