Journal article
Cyclic Multiplexed-Immunofluorescence (cmIF), a Highly Multiplexed Method for Single-Cell Analysis
Methods in molecular biology (Clifton, N.J.), v 2055, pp 521-562
01 Jan 2020
PMID: 31502168
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Immunotherapy harnesses the power of the adaptive immune system and has revolutionized the field of oncotherapy, as novel therapeutic strategies have been introduced into clinical use. The development of immune checkpoint inhibitors has led to durable control of disease in a subset of advanced cancer patients, such as those with melanoma and non-small cell lung cancer. However, predicting patient responses to therapy remains a major challenge, due to the remarkable genomic, epigenetic, and microenvironmental heterogeneity present in each tumor. Breast cancer (BC) is the most common cancer in women, where hormone receptor-positive (HR+; estrogen receptor and/or progesterone receptor) BC comprises the majority (>50%) and has better prognosis, while a minority (<20%) are triple negative BC (TNBC), which has an aggressive phenotype. There is a clinical need to identify predictors of late recurrence in HR+ BC and predictors of immunotherapy outcomes in advanced TNBC. Tumor-infiltrating lymphocytes (TILs) have recently been shown to predict late recurrence in HR+, counter to the findings that TILs confer good prognosis in TNBC and human epidermal growth factor receptor 2 positive (HER2+) subtypes. Furthermore, the spatial arrangement of TILs also appears to have prognostic value, with dense clusters of immune cells predicting poor prognosis in HR+ and good prognosis in TNBC. Whether TIL clusters in different breast cancer subtypes represent the same or different landscapes of TILs is unknown and may have treatment implications for a significant portion of breast cancer patients. Current histopathological staining technology is not sufficient for characterizing the ensembles of TILs and their spatial patterns, in addition to tumor and microenvironmental heterogeneity. However, recent advances in cyclic immunofluorescence enable differentiation of the subsets based on TILs, tumor heterogeneity, and microenvironment composition between good and poor responders. A computational framework for understanding the importance of the spatial relationships between TILs and tumor cells in cancer tissues, which will allow for quantitative interpretation of cyclic immunostaining, is also under development. This chapter will explore the workflow for a newly developed cyclic multiplexed-immunofluorescence (cmIF) assay, which has been optimized for formalin-fixed. paraffin-embedded tissues and developed to process digital images for quantitative single-cell based spatial analysis of tumor heterogeneity and microenvironment, including immune cell composition.
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Details
- Title
- Cyclic Multiplexed-Immunofluorescence (cmIF), a Highly Multiplexed Method for Single-Cell Analysis
- Creators
- Jennifer Eng - Oregon Health & Science UniversityGuillaume Thibault - Oregon Health & Science UniversityShiuh-Wen Luoh - Oregon Health & Science UniversityJoe W Gray - Oregon Health & Science UniversityYoung Hwan Chang - Oregon Health & Science UniversityKoei Chin - Oregon Health & Science University
- Publication Details
- Methods in molecular biology (Clifton, N.J.), v 2055, pp 521-562
- Publisher
- Springer Nature
- Grant note
- R44 CA224994 / NCI NIH HHS U54 CA209988 / NCI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000545539400025
- Scopus ID
- 2-s2.0-85071978059
- Other Identifier
- 1493997734; 9781493997732; 991021838123304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemical Research Methods
- Immunology
- Oncology