Multiplex bioimaging of single-cell spatial profiles for precision cancer diagnostics and therapeutics

Allam, Mayar; Cai, Shuangyi; Coşkun, Ahmet F.

doi:10.1038/s41698-020-0114-1

Cited by 71 publications

(48 citation statements)

References 133 publications

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“…Mass-spectroscopy-based imaging can directly provide the molecular/atomic composition of the sample. However, it is a destructive technology in which samples are dissociated and the relative components are differentiated and interpreted by mass selection [ 14 ]. Therefore, there is still a need for novel biophotonic devices allowing rapid, high-throughput metabolic profiling and immunophenotyping at the single-cancer cell level.…”

Section: Discussionmentioning

confidence: 99%

Raman Microscopy: Progress in Research on Cancer Cell Sensing

Satheeshkumar

Managò

Luca

2020

Sensors

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In the last decade, Raman Spectroscopy (RS) was demonstrated to be a label-free, non-invasive and non-destructive optical spectroscopy allowing the improvement in diagnostic accuracy in cancer and analytical assessment for cell sensing. This review discusses how Raman spectra can lead to a deeper molecular understanding of the biochemical changes in cancer cells in comparison to non-cancer cells, analyzing two key examples, leukemia and breast cancer. The reported Raman results provide information on cancer progression and allow the identification, classification, and follow-up after chemotherapy treatments of the cancer cells from the liquid biopsy. The key obstacles for RS applications in cancer cell diagnosis, including quality, objectivity, number of cells and velocity of the analysis, are considered. The use of multivariant analysis, such as principal component analysis (PCA) and linear discriminate analysis (LDA), for an automatic and objective assessment without any specialized knowledge of spectroscopy is presented. Raman imaging for cancer cell mapping is shown and its advantages for routine clinical pathology practice and live cell imaging, compared to single-point spectral analysis, are debated. Additionally, the combination of RS with microfluidic devices and high-throughput screening for improving the velocity and the number of cells analyzed are also discussed. Finally, the combination of the Raman microscopy (RM) with other imaging modalities, for complete visualization and characterization of the cells, is described.

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Section: Discussionmentioning

confidence: 99%

Raman Microscopy: Progress in Research on Cancer Cell Sensing

Satheeshkumar

Managò

Luca

2020

Sensors

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“…However, until recently, conventional histological techniques lacked the ability to measure the expression of a multitude of proteins at subcellular resolution while preserving spatial information 21,22 . Advancements in high-dimensional multiplexed imaging, such as through the development of multiplexed ion beam imaging (MIBI), have allowed for more direct interrogation of the TIME 23 while boosting standardization and reproducibility of results 24 . MIBI uses secondary ion mass spectrometry to image antibodies tagged with isotopically pure elemental reporters 25 .…”

Section: Introductionmentioning

confidence: 99%

Multiplexed Imaging Analysis of the Tumor-Immune Microenvironment Reveals Predictors of Outcome in Triple-Negative Breast Cancer

Patwa

Yamashita

Jin

et al. 2021

Preprint

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Triple-negative breast cancer (TNBC), the poorest-prognosis breast cancer subtype, lacks clinically approved biomarkers for patient risk stratification, treatment management, and immunotherapies. Prior literature has shown that interrogation of the tumor-immune microenvironment (TIME) may be a promising approach for the discovery of novel biomarkers that can fill these gaps. Recent developments in high-dimensional tissue imaging technology, such as multiplexed ion beam imaging (MIBI), provide spatial context to protein expression in the TIME, opening doors for in-depth characterization of cellular processes. We developed a computational pipeline for the robust examination of the TIME using MIBI. We discover that profiling the functional proteins involved in cell-to-cell interactions in the TIME predicts recurrence and overall survival in TNBC. The interactions between CD45RO and Beta Catenin and CD45RO and HLA-DR were the most relevant for patient stratification. We demonstrated the clinical relevance of the immunoregulatory proteins PD-1, PD-L1, IDO, and Lag3 by tying their interactions to recurrence and survival. Multivariate analysis revealed that our methods provide additional prognostic information compared to clinical variables. Our novel computational pipeline produces interpretable results, and is generalizable to other cancer types.

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“…Recently, the TME has become an important therapeutic target ( Lin et al, 2019 , 2020 ). In addition, the spatial heterogeneity of tumors has caused substantial challenges for tumor treatment ( Allam et al, 2020 ). There are hundreds to thousands of subclones in each tumor, which makes it difficult for researchers to fully understand the TME in different areas of the tumor.…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Analysis Reveals Spatial Heterogeneity of Immune Cells in Lung Adenocarcinoma

Wang

Shu

et al. 2021

Front. Cell Dev. Biol.

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The impacts of the tumor microenvironment (TME) on tumor evolvability remain unclear. A challenge for nearly all cancer types is spatial heterogeneity, providing substrates for the emergence and evolvability of drug resistance and leading to unfavorable prognosis. Understanding TME heterogeneity among different tumor sites would provide deeper insights into personalized therapy. We found 9,992 cell profiles of the TME in human lung adenocarcinoma (LUAD) samples at a single-cell resolution. By comparing different tumor sites, we discovered high TME heterogeneity. Single-sample gene set enrichment analysis (ssGSEA) was utilized to explore functional differences between cell subpopulations and between the core, middle and edge of tumors. We identified 8 main cell types and 27 cell subtypes of T cells, B cells, fibroblasts and myeloid cells. We revealed CD4+ naive T cells in the tumor core that express high levels of immune checkpoint molecules and have a higher activity of immune-exhaustion signaling. CD8+ T cell subpopulations in the tumor core correlate with the upregulated activity of transforming growth factor-β (TGF-β) and fibroblast growth factor receptor (FGFR) signaling and downregulated T cell activity. B cell subtypes in the tumor core downregulate cytokine production. In this study, we revealed that there was immunological heterogeneity in the TME of patients with LUAD that have different ratios of immune cells and stromal cells, different functions, and various degrees of activation of immune-related pathways in different tumor parts. Therefore, clarifying the spatial heterogeneity of the tumor in the immune microenvironment can help clinicians design personalized treatments.

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Multiplex bioimaging of single-cell spatial profiles for precision cancer diagnostics and therapeutics

Cited by 71 publications

References 133 publications

Raman Microscopy: Progress in Research on Cancer Cell Sensing

Raman Microscopy: Progress in Research on Cancer Cell Sensing

Multiplexed Imaging Analysis of the Tumor-Immune Microenvironment Reveals Predictors of Outcome in Triple-Negative Breast Cancer

Single-Cell Analysis Reveals Spatial Heterogeneity of Immune Cells in Lung Adenocarcinoma

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