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World J Gastroenterol. Jul 21, 2018; 24(27): 2995-3005
Published online Jul 21, 2018. doi: 10.3748/wjg.v24.i27.2995
Multiparametric analysis of colorectal cancer immune responses
Julia KH Leman, Sarah K Sandford, Janet L Rhodes, Roslyn A Kemp
Julia KH Leman, Sarah K Sandford, Janet L Rhodes, Roslyn A Kemp, Department of Microbiology and Immunology, University of Otago, Dunedin 9010, New Zealand
Author contributions: All authors contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Roslyn A Kemp, PhD, Associate Professor, Department of Microbiology and Immunology, University of Otago, PO Box 56, 720 Cumberland St, Dunedin 9010, New Zealand. roslyn.kemp@otago.ac.nz
Telephone: +64-3-4797708 Fax: +64-3-4798540
Received: March 28, 2018
Peer-review started: March 29, 2018
First decision: May 16, 2018
Revised: May 23, 2018
Accepted: June 16, 2018
Article in press: June 16, 2018
Published online: July 21, 2018
Processing time: 112 Days and 10 Hours
Abstract

Colorectal cancer (CRC) is a heterogeneous disease, with a diverse and plastic immune cell infiltrate. These immune cells play an important role in regulating tumour growth - progression or elimination. Some populations of cells have a strong correlation with disease-free survival, making them useful prognostic markers. In particular, the infiltrate of CD3+ and CD8+ T cells into CRC tumours has been validated worldwide as a valuable indicator of patient prognosis. However, the heterogeneity of the immune response, both between patients with tumours of different molecular subtypes, and within the tumour itself, necessitates the use of multiparametric analysis in the investigation of tumour-specific immune responses. This review will outline the multiparametric analysis techniques that have been developed and applied to studying the role of immune cells in the tumour, with a focus on colorectal cancer. Because much of the data in this disease relates to T cell subsets and heterogeneity, we have used T cell populations as examples throughout. Flow and mass cytometry give a detailed representation of the cells within the tumour in a single-cell suspension on a per-cell basis. Imaging technologies, such as imaging mass cytometry, are used to investigate increasing numbers of markers whilst retaining the spatial and structural information of the tumour section and the infiltrating immune cells. Together, the analyses of multiple immune parameters can provide valuable information to guide clinical decision-making in CRC.

Keywords: Colorectal cancer; Flow cytometry; Immune cells; Multiparametric analysis; Immunohistochemistry; Mass cytometry; Microscopy

Core tip: Colorectal cancer (CRC) is a heterogeneous disease. The immune response to CRC is highly variable, clinically relevant, and as yet poorly characterised. Clinical management of this disease is still relatively uniform, and does not yet accommodate the influence of immune response on patient outcomes. Multiparametric analysis of CRC is the best approach to describe the immune response. Improved understanding of immune responses to CRC will guide patient management, improved survival, and identify new potential therapeutic biomarkers. This review summarises currently available modes of multiparametric analysis, their advantages and drawbacks, and their clinical relevance.