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

被引:9
作者
Toh, James Wei Tatt [1 ]
Ferguson, Angela L. [2 ]
Spring, Kevin J. [3 ]
Mahajan, Hema [4 ]
Palendira, Umaimainthan [5 ]
机构
[1] Univ Sydney, Westmead Hosp, Ingham Inst Appl Med Res,Westmead Clin Sch, Div Surg & Anaesthesia,Dept Colorectal Surg, Westmead, NSW 2145, Australia
[2] Univ Sydney, Dept Infect Dis & Immunol, Sch Med Sci,Fac Med & Hlth,Charles Perkin Ctr, Human Viral & Canc Immunol,Centenary Inst, Sydney, NSW 2000, Australia
[3] Univ Western Sydney, Liverpool Hosp, Med Oncol Grp,Ingham Inst Appl Med Res, Liverpool Clin Sch,South Western Clin Sch UNSW, Liverpool, NSW 2170, Australia
[4] Westmead Hosp, ICPMR, Dept Anat Pathol, Westmead, NSW 2145, Australia
[5] Univ Sydney, Fac Med & Hlth, Sch Med Sci, Dept Immunol & Infect Dis, Sydney, NSW 2000, Australia
关键词
Tissue resident memory cells; Resident memory T cells; Colorectal cancer; Microsatellite instability; BRAF; DNA mismatch repair; Immunotherapy; Prognosis; TUMOR-INFILTRATING LYMPHOCYTES; ANTITUMOR IMMUNITY; PROGNOSTIC-FACTOR; CD8(+); SURVIVAL; CD103; RESPONSES; FEATURES; PLAYERS; PD-1;
D O I
10.5306/wjco.v12.i4.238
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 inForm 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 andMSI-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.
引用
收藏
页码:238 / 248
页数:11
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