Immunohistochemical Characterization of Tumor-Associated Macrophages in Canine Lymphomas.

Sergio Vázquez,Raquel Vallejo,Valentín Pérez,José A Vega,José Espinosa,Noive Arteche

doi:10.3390/ani11082301

Sergio Vázquez, Raquel Vallejo + Show 4 more

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https://doi.org/10.3390/ani11082301

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Abstract

Simple SummaryIn human lymphomas, it has been shown that the macrophages present in the tumor have an influence on their behavior; however, studies on this topic are scarce in veterinary medicine. The aim of this work was to determine the relationship between the amount and type of macrophage infiltrates with histological grade and immunophenotype in cases of canine lymphoma. Samples from the lymph nodes of 25 dogs with lymphoma were analyzed. Immunohistochemistry was used to determine the tumor immunophenotype (CD3 and CD20 antibodies) and the macrophage characterization (Iba1, CD163, iNOS and MAC387 antibodies). Results showed that the highest number of macrophages were found in high-grade and B-cell lymphomas; the latter also presented the greatest amount of M1 and M2 macrophages. High-grade lymphomas showed a greater number of M2 and recently recruited macrophages that were most abundant in T than in B-cell lymphomas. In conclusion, the number and type of macrophages present in canine lymphoma are related to the immunophenotype and the grade. In those with a high grade, macrophages are actively recruited and show a predominant M2 phenotype, which has been associated with a protumoral activity.Macrophages have been confirmed to play a significant role in the behavior of human lymphomas, albeit no consistent data are so far available in canine lymphomas. The present study characterizes the macrophages present in cases of canine nodal lymphoma and their relationship with the histological grade and the immunophenotype. Samples from the lymph nodes of 25 dogs diagnosed with lymphoma were selected. Immunohistochemistry was used to determine the tumor immunophenotype (CD3 and CD20 antibodies) and macrophage characterization (Iba1, MAC387, CD204, CD163 and iNOS antibodies). Macrophage counting was performed in 10 randomly selected, high-power fields per sample. Generalized linear models with Poisson distribution were used for statistical analysis. A significantly greater number of macrophages (Iba1+) were detected in high-grade and B-cell lymphomas. The highest amount of both M1 (iNOS+) and M2 (CD204+ and CD163+) subtypes were observed in B-cell lymphomas. High-grade lymphomas showed a greater number of CD204+ and CD163+ cells and recently recruited MAC387+ macrophages. The latter were most abundant in T than in B-cell lymphomas. In conclusion, a significant population of macrophages is present in canine lymphomas, which constitute a heterogeneous population that shows variations in the amount and immunohistochemical profile according to the histological grade and immunophenotype.

Highlights

Non-tumor cells present in the tissues affected by a neoplasm play an essential role in the development and spread of a tumor so that, among other functions, it can allow the host immune system evasion, directly or indirectly, by the release of modulating major bioactive molecules [1]
This study has demonstrated that a significant population of macrophages is present in canine lymphomas with variations in the amount and cell subtypes in relation to the histological grade (HG) and IPT
In those with a high grade, macrophages are actively recruited and show a predominant M2 phenotype associated with a protumoral activity, in contrast to low-grade lymphomas with lower numbers of macrophages and a predominant M1 subtype

Summary

Introduction

Non-tumor cells present in the tissues affected by a neoplasm play an essential role in the development and spread of a tumor so that, among other functions, it can allow the host immune system evasion, directly or indirectly, by the release of modulating major bioactive molecules [1]. Tumor-associated macrophages (TAM) are one of the main cells responsible for the maintenance of the tumor microenvironment. They represent the main escape route of the neoplasia by the active suppression of the immune system and the modulation of other tumor microenvironment cell types [3,4]. In the majority of the human tumors, including some types of lymphoma, M2 predominate over M1 macrophages and this difference is related to their histological grade (HG) [11,12,13,14]

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