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The Dog as a Model to Study the Tumor Microenvironment

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Tumor Microenvironment

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1329))

Abstract

Cancer is a complex and dynamic disease with an outcome that depends on a strict crosstalk between tumor cells and other components in tumor microenvironment, namely, tumor-infiltrating immune cells, fibroblasts, cancer stem cells, adipocytes, and endothelial cells. Within the tumor microenvironment, macrophages and T-lymphocytes appear to be key effectors during the several steps of tumor initiation and progression. Tumor cells, through the release of a plethora of signaling molecules, can induce immune tolerance, by avoiding immune surveillance, and inhibit immune cells cytotoxic functions. Furthermore, as the tumor grows, tumor microenvironment reveals a series of dysfunctional conditions that potentiate a polarization of harmful humoral Th2 and Th17, an upregulation of Treg cells, and a differentiation of macrophages into the M2 subtype, which contribute to the activation of several signaling pathways involving important tissue biomarkers (COX-2, EGFR, VEGF) implicated in cancer aggressiveness and poor clinical outcomes. In order to maintain the tumor growth, cancer cells acquire several adaptations such as neovascularization and metabolic reprogramming. An extensive intracellular production of lactate and protons is observed in tumor cells as a result of their high glycolytic metabolism. This contributes not only for the microenvironment pH alteration but also to shape the immune response that ultimately impairs immune cells capabilities and effector functions.

In this chapter, the complexity of tumor microenvironment, with special focus on macrophages, T-lymphocytes, and the impact of lactate efflux, was reviewed, always trying to demonstrate the strong similarities between data from studies of humans and dogs, a widely proposed model for comparative oncology studies.

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Author information

Author notes

  1. Maria I. Carvalho and Teresa P. Raposo contributed equally to this work and share the first authorship.

Authors and Affiliations

  1. Faculdade de Medicina Veterinária, Universidade Lusófona de Humanidades e Tecnologias, Lisbon, Portugal

    Maria I. Carvalho

  2. Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal

    Teresa P. Raposo & Felisbina L. Queiroga

  3. CEB – Centre of Biological Engineering, University of Minho, Braga, Portugal

    Ricardo Silva-Carvalho

  4. Animal and Veterinary Research Centre (CECAV), University of Trás-os-Montes and Alto Douro, Vila Real, Portugal

    Isabel Pires & Justina Prada

  5. CHV – Veterinary Hospital, Porto, Portugal

    Hugo Gregório

  6. Centre for research and Technologies Agro-environmental and Biological sciences (CITAB), University of Trás-os-Montes and Alto Douro, Vila Real, Portugal

    Felisbina L. Queiroga

  7. Centre for the Study of Animal Sciences, CECA-ICETA, University of Porto, Porto, Portugal

    Felisbina L. Queiroga

Authors
  1. Maria I. Carvalho
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  2. Teresa P. Raposo
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  3. Ricardo Silva-Carvalho
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  4. Isabel Pires
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  5. Justina Prada
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  6. Hugo Gregório
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  7. Felisbina L. Queiroga
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Corresponding author

Correspondence to Felisbina L. Queiroga .

Editor information

Editors and Affiliations

  1. Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Alexander Birbrair

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Carvalho, M.I. et al. (2021). The Dog as a Model to Study the Tumor Microenvironment. In: Birbrair, A. (eds) Tumor Microenvironment. Advances in Experimental Medicine and Biology, vol 1329. Springer, Cham. https://doi.org/10.1007/978-3-030-73119-9_7

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