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Toward precision immunotherapy using multiplex immunohistochemistry and in silico methods to define the tumor immune microenvironment

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Abstract

Recent developments in cancer immunotherapy promise better outcomes for cancer patients, although clinical trials for difficult to treat cancers such as malignant brain cancer present special challenges, showing little response to first generation immunotherapies. Reasons for differences in immunotherapy response in some cancer types are likely due to the nature of tumor microenvironment, which harbors multiple cell types which interact with tumor cells to establish immunosuppression. The cell types which appear to hold the key in regulating tumor immunosuppression are the tumor-infiltrating immune cells. The current standard treatment for difficult to treat cancer, including the most malignant brain cancer, glioblastoma, continues to offer a bleak outlook for patients. Immune-profiling and correlation with pathological and clinical data will lead to a deeper understanding of the tumor immune microenvironment and contribute toward the selection, optimization and development of novel precision immunotherapies. Here, we review the current understanding of the tumor microenvironmental landscape in glioblastoma with a focus on next-generation technologies including multiplex immunofluorescence and computational approaches to map the brain tumor microenvironment to decipher the role of the immune system in this lethal malignancy.

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Funding

We acknowledge the support of the CASS Foundation (Grant no. 28534), The Royal Melbourne Hospital Neuroscience Foundation, and the Brain Foundation, Australia. SW was supported by the Australia Awards Scholarship from the Department of Foreign Affairs and Trade of Australia. PKD was supported by a NHMRC Senior Research Fellowship (APP1136680).

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  1. Samuel S. Widodo and Ryan A. Hutchinson contributed equally.

Authors and Affiliations

  1. Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Australia

    Samuel S. Widodo, Yitong Fang, Alexander D. Barrow & Theo Mantamadiotis

  2. Department of Clinical Pathology, The University of Melbourne, Melbourne, Australia

    Ryan A. Hutchinson

  3. Victorian Comprehensive Cancer Centre, University of Melbourne Centre for Cancer Research, Parkville, Australia

    Ryan A. Hutchinson

  4. Bioinformatics Division, The Walter and Eliza Hall Institute, Parkville, Australia

    Stefano Mangiola

  5. Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia

    Paul J. Neeson & Phillip K. Darcy

  6. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia

    Paul J. Neeson & Phillip K. Darcy

  7. Department of Surgery, The University of Melbourne, Parkville, Australia

    Christopher M. Hovens, Marija Dinevska, Stanley S. Stylli & Theo Mantamadiotis

  8. Department of Neurosurgery, Royal Melbourne Hospital, Parkville, Australia

    Stanley S. Stylli

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SW, RAH and TM conceptualized the review. SW, YF, SM provided data for and prepared the figures. All authors contributed to the writing and editing of the review. All authors approved the final version.

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Correspondence to Theo Mantamadiotis.

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RAH has ongoing research collaborations with Definiens GmbH and Ultivue Inc.

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Widodo, S.S., Hutchinson, R.A., Fang, Y. et al. Toward precision immunotherapy using multiplex immunohistochemistry and in silico methods to define the tumor immune microenvironment. Cancer Immunol Immunother 70, 1811–1820 (2021). https://doi.org/10.1007/s00262-020-02801-7

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