Abstract PO-041: Multiplexed ion beam imaging to describe tumor-immune microenvironment and tumor heterogeneity in neuroblastoma

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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Multiplexed imaging analysis of the tumor-immune microenvironment reveals predictors of outcome in triple-negative breast cancer

Communications Biology ◽

10.1038/s42003-021-02361-1 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Aalok Patwa ◽

Rikiya Yamashita ◽

Jin Long ◽

Tyler Risom ◽

Michael Angelo ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Ion Beam ◽

Breast Cancer Subtype ◽

Tissue Imaging ◽

Immune Microenvironment ◽

Prognostic Information ◽

Tumor Immune Microenvironment ◽

Prior Literature

AbstractTriple-negative breast cancer, the poorest-prognosis breast cancer subtype, lacks clinically approved biomarkers for patient risk stratification and treatment management. Prior literature has shown that interrogation of the tumor-immune microenvironment may be a promising approach to fill these gaps. Recently developed high-dimensional tissue imaging technology, such as multiplexed ion beam imaging, provide spatial context to protein expression in the microenvironment, allowing in-depth characterization of cellular processes. We demonstrate that profiling the functional proteins involved in cell-to-cell interactions in the microenvironment can predict recurrence and overall survival. We highlight the immunological relevance of the immunoregulatory proteins PD-1, PD-L1, IDO, and Lag3 by tying interactions involving them to recurrence and survival. Multivariate analysis reveals that our methods provide additional prognostic information compared to clinical variables. In this work, we present a computational pipeline for the examination of the tumor-immune microenvironment using multiplexed ion beam imaging that produces interpretable results, and is generalizable to other cancer types.

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Multiscale Agent-Based and Hybrid Modeling of the Tumor Immune Microenvironment

Processes ◽

10.3390/pr7010037 ◽

2019 ◽

Vol 7 (1) ◽

pp. 37 ◽

Cited By ~ 30

Author(s):

Kerri-Ann Norton ◽

Chang Gong ◽

Samira Jamalian ◽

Aleksander Popel

Keyword(s):

Immune Response ◽

Tumor Heterogeneity ◽

Computational Models ◽

Digital Pathology ◽

Hybrid Modeling ◽

Immune Microenvironment ◽

Agent Based ◽

Tumor Immune Microenvironment ◽

Cancer Tumor

Multiscale systems biology and systems pharmacology are powerful methodologies that are playing increasingly important roles in understanding the fundamental mechanisms of biological phenomena and in clinical applications. In this review, we summarize the state of the art in the applications of agent-based models (ABM) and hybrid modeling to the tumor immune microenvironment and cancer immune response, including immunotherapy. Heterogeneity is a hallmark of cancer; tumor heterogeneity at the molecular, cellular, and tissue scales is a major determinant of metastasis, drug resistance, and low response rate to molecular targeted therapies and immunotherapies. Agent-based modeling is an effective methodology to obtain and understand quantitative characteristics of these processes and to propose clinical solutions aimed at overcoming the current obstacles in cancer treatment. We review models focusing on intra-tumor heterogeneity, particularly on interactions between cancer cells and stromal cells, including immune cells, the role of tumor-associated vasculature in the immune response, immune-related tumor mechanobiology, and cancer immunotherapy. We discuss the role of digital pathology in parameterizing and validating spatial computational models and potential applications to therapeutics.

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

10.21203/rs.3.rs-132431/v1 ◽

2021 ◽

Author(s):

Aalok Patwa ◽

Rikiya Yamashita ◽

Jin Long ◽

Leeat Keren ◽

Michael R. Angelo ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Ion Beam ◽

Breast Cancer Subtype ◽

Beta Catenin ◽

Computational Pipeline ◽

Immune Microenvironment ◽

Prognostic Information ◽

Tumor Immune Microenvironment

Abstract 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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NIR-active Nanoterminator with Mature Dendritic Cell Acitivities for Immuno-Priming Mild Photothermal Cancer Therapy

10.26434/chemrxiv.12546698 ◽

2020 ◽

Author(s):

zhihong sun ◽

Guanjun Deng ◽

Xinghua Peng ◽

Xiuli Xu ◽

Lanlan Liu ◽

...

Keyword(s):

Dendritic Cell ◽

Photothermal Therapy ◽

Whole Body ◽

Mature Dendritic Cell ◽

Immune Microenvironment ◽

Highly Efficient ◽

Tumor Immune Microenvironment ◽

Shock Proteins ◽

Mild Temperature ◽

Broad Interest

Recently, photothermal-immuno synergistic therapy under mild temperature (~ 45 °C) has got broad interest in cancer treatment. Inhibition the intratumorally HSPs production is the key to accomplish highly efficient and mild photothermal therapy. In this work, we developed biomimetic nanoterminators with mature DCs functions by coating the mature dendritic cell membrane on photothermal nanoagents. As-prepared nanoterminators could automatically locate on T cell in the complex tumor-immune microenvironment and promote the T cells proliferation, activation and cytokine secretion, which could not only inhibit the expression of heat shock proteins to cooperate on highly efficient mild photothermal therapy (~42°C), but also promote tumor apoptosis during the treatment. More importantly, this nanoterminator could serve as vaccine to trigger anti-tumor immune response of the whole body, which would be promising to long-life tumor inhibition and termination.

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