Copyright
©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Cytotoxic CD8+ T cells and tissue resident memory cells in colorectal cancer based on microsatellite instability and BRAF status
James Wei Tatt Toh, Angela L Ferguson, Kevin J Spring, Hema Mahajan, Umaimainthan Palendira
James Wei Tatt Toh, Division of Surgery and Anaesthesia, Department of Colorectal Surgery, Westmead Hospital, Westmead Clinical School, The University of Sydney, Ingham Institute for Applied Medical Research, Westmead 2145, NSW, Australia
Angela L Ferguson, Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine and Health, Human Viral & Cancer Immunology, Centenary Institute, Charles Perkin Centre, The University of Sydney, Sydney 2000, NSW, Australia
Kevin J Spring, Medical Oncology Group, Ingham Institute for Applied Medical Research, Liverpool Hospital, Liverpool Clinical School, University of Western Sydney, South Western Clinical School UNSW, Liverpool 2170, NSW, Australia
Hema Mahajan, Department of Anatomical Pathology, ICPMR, Westmead Hospital, Westmead 2145, NSW, Australia
Umaimainthan Palendira, Department of Immunology and Infectious Diseases, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney 2000, NSW, Australia
Author contributions: Toh JWT and Ferguson A are co-first authors; Toh JWT, Ferguson A and Palendira U conceptualized and designed the study experimental and analytical methods; Toh JWT wrote the manuscript; Palendira U and Spring KJ supervised the project; Toh JWT, Ferguson A, Palendira U, Spring KJ and Mahajan H were involved in critical revisions of the manuscript.
Institutional review board statement: This study was reviewed and approved by the Executive Ethical Review Panel of the Sydney Local Health District - CRGH Human Research Ethics Committee.
Conflict-of-interest statement: The authors declare no conflicts of interest and have no financial disclosures.
Data sharing statement: Data supporting the results in the paper available on request.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: James Wei Tatt Toh, BSc, MBBS, Senior Lecturer, Surgeon, Division of Surgery and Anaesthesia, Department of Colorectal Surgery, Westmead Hospital, Cnr Hawkesbury and Darcy Rd, Westmead 2145, NSW, Australia. james.toh@sydney.edu.au
Received: January 14, 2021
Peer-review started: January 14, 2021
First decision: February 15, 2021
Revised: March 14, 2021
Accepted: April 5, 2021
Article in press: April 5, 2021
Published online: April 24, 2021
ARTICLE HIGHLIGHTS
Research background
The presence of resident memory T (TRM) cells has already been reported in studies of high-grade serous ovarian cancer patients, non-small cell lung carcinoma patients and breast cancer, but there has been limited evidence on TRM cells in the scientific literature in colorectal cancer (CRC). This is a landmark study on TRM cells in CRC.
Research motivation
With TRM cells showing promise in several solid organ tumour studies, the premise of this study was to evaluate if TRM cells are present in CRC and thus potentially be a target for immunotherapy/novel target therapy in the future.
Research objectives
The objective of this study was to examine the potential role of TRM cells in providing immunogenicity in CRC stratified by microsatellite instability (MSI) and BRAF status.
Research methods
Formalin fixed paraffin embedded tumour sections were successfully stained using quantitative multiplex IHC staining. All IHC staining was performed using an Opal Multiplex immunohistochemistry (IHC) assay kit (PerkinElmer, Waltham, MA, United States) and optimised in-house.
Research results
This study has shown that CD8+ TRM are found in greater abundance in both high level MSI (MSI-H):BRAF mutant and MSI-H:BRAF wild type CRC when compared with their microsatellite stable (MSS) counterpart. CD8+ TRM may play a role in the immunogenicity in both BRAF mutant and BRAF wild type MSI-H CRC. The abundance of TRM cells may contribute to the favourable prognosis observed in MSI-H CRC when compared to MSS CRC.
Research conclusions
TRM cells are found in greater abundance and contributes to the immunogenicity of MSI-H CRCs.
Research perspectives
TRM cells may be a target for immunotherapy/novel target therapy in MSI-H CRCs, and future research should focus on the potential value of TRM cells, as well as therapeutic agents that may stimulate TRM activity or adoptive cell transfer aimed at harvesting and utilizing the patients' own immune cells such as specially altered T-cells to precisely and specifically target cancer cells.
