Metastatic immune infiltrates correlate with those of the primary tumour in canine osteosarcoma

Sita S. Withers, Daniel York, Jin W. Choi, Kevin D Woolard, Renee Laufer-Amorim, Ellen E. Sparger, Jenna H Burton, Stephen J Mcsorley, Arta M Monjazeb, William J Murphy, Robert J Canter, Robert B Rebhun

Research output: Contribution to journalArticle

Abstract

Our lack of understanding of the immune microenvironment in canine osteosarcoma (cOSA) has limited the identification of potential immunotherapeutic targets. In particular, our ability to utilize readily available tissue from a dog's primary tumour to predict the type and extent of immune response in their pulmonary metastatic lesions is unknown. We, therefore, collected 21 matched pairs of primary tumours and pulmonary metastatic lesions from dogs with OSA and performed immunohistochemistry to quantify T-lymphocyte (CD3), FOXP3+ cell, B-lymphocyte (Pax-5), and CD204+ macrophage infiltration. We found that T-lymphocytes and FOXP3+ infiltrates in primary tumours positively correlated with that of metastatic lesions (ρ = 0.512, P = 0.038 and ρ = 0.698, P = 0.007, respectively), while a strong trend existed for CD204+ infiltrates (ρ = 0.404, P = 0.087). We also observed T- and B-lymphocytes, and CD204+ macrophages to be significantly higher in a dog's pulmonary metastasis compared to their primary tumour (P = 0.018, P = 0.018, P = 0.016, respectively), while FOXP3+ cells were only significantly higher in metastases when all primary tumour and metastasis lesions were compared without pairing (P = 0.036). Together, these findings suggest that the metastatic immune microenvironment may be influenced by that of the primary cOSA, and that primary tumour immune biomarkers could potentially be applied to predict immunotherapeutic responses in gross metastatic disease. We, therefore, provide a rationale for the treatment of cOSA pulmonary metastases with immunotherapeutics that enhance the anti-tumour activity of these immune cells, particularly in dogs with moderate to high immune cell infiltration in their primary tumours.

Original languageEnglish (US)
JournalVeterinary and Comparative Oncology
DOIs
StatePublished - Jan 1 2019

Fingerprint

osteosarcoma
Osteosarcoma
Canidae
neoplasms
dogs
lesions (animal)
metastasis
Neoplasms
Dogs
Neoplasm Metastasis
lungs
Lung
T-lymphocytes
B-Lymphocytes
B-lymphocytes
Macrophages
macrophages
T-Lymphocytes
cells
Tumor Biomarkers

Keywords

  • dogs
  • immunotherapy
  • neoplasm metastasis
  • osteosarcoma
  • tumour microenvironment

ASJC Scopus subject areas

  • veterinary(all)

Cite this

@article{a20e328167ec4aafb67d4acf99afb90c,
title = "Metastatic immune infiltrates correlate with those of the primary tumour in canine osteosarcoma",
abstract = "Our lack of understanding of the immune microenvironment in canine osteosarcoma (cOSA) has limited the identification of potential immunotherapeutic targets. In particular, our ability to utilize readily available tissue from a dog's primary tumour to predict the type and extent of immune response in their pulmonary metastatic lesions is unknown. We, therefore, collected 21 matched pairs of primary tumours and pulmonary metastatic lesions from dogs with OSA and performed immunohistochemistry to quantify T-lymphocyte (CD3), FOXP3+ cell, B-lymphocyte (Pax-5), and CD204+ macrophage infiltration. We found that T-lymphocytes and FOXP3+ infiltrates in primary tumours positively correlated with that of metastatic lesions (ρ = 0.512, P = 0.038 and ρ = 0.698, P = 0.007, respectively), while a strong trend existed for CD204+ infiltrates (ρ = 0.404, P = 0.087). We also observed T- and B-lymphocytes, and CD204+ macrophages to be significantly higher in a dog's pulmonary metastasis compared to their primary tumour (P = 0.018, P = 0.018, P = 0.016, respectively), while FOXP3+ cells were only significantly higher in metastases when all primary tumour and metastasis lesions were compared without pairing (P = 0.036). Together, these findings suggest that the metastatic immune microenvironment may be influenced by that of the primary cOSA, and that primary tumour immune biomarkers could potentially be applied to predict immunotherapeutic responses in gross metastatic disease. We, therefore, provide a rationale for the treatment of cOSA pulmonary metastases with immunotherapeutics that enhance the anti-tumour activity of these immune cells, particularly in dogs with moderate to high immune cell infiltration in their primary tumours.",
keywords = "dogs, immunotherapy, neoplasm metastasis, osteosarcoma, tumour microenvironment",
author = "Withers, {Sita S.} and Daniel York and Choi, {Jin W.} and Woolard, {Kevin D} and Renee Laufer-Amorim and Sparger, {Ellen E.} and Burton, {Jenna H} and Mcsorley, {Stephen J} and Monjazeb, {Arta M} and Murphy, {William J} and Canter, {Robert J} and Rebhun, {Robert B}",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/vco.12459",
language = "English (US)",
journal = "Veterinary and Comparative Oncology",
issn = "1476-5829",
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TY - JOUR

T1 - Metastatic immune infiltrates correlate with those of the primary tumour in canine osteosarcoma

AU - Withers, Sita S.

AU - York, Daniel

AU - Choi, Jin W.

AU - Woolard, Kevin D

AU - Laufer-Amorim, Renee

AU - Sparger, Ellen E.

AU - Burton, Jenna H

AU - Mcsorley, Stephen J

AU - Monjazeb, Arta M

AU - Murphy, William J

AU - Canter, Robert J

AU - Rebhun, Robert B

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Our lack of understanding of the immune microenvironment in canine osteosarcoma (cOSA) has limited the identification of potential immunotherapeutic targets. In particular, our ability to utilize readily available tissue from a dog's primary tumour to predict the type and extent of immune response in their pulmonary metastatic lesions is unknown. We, therefore, collected 21 matched pairs of primary tumours and pulmonary metastatic lesions from dogs with OSA and performed immunohistochemistry to quantify T-lymphocyte (CD3), FOXP3+ cell, B-lymphocyte (Pax-5), and CD204+ macrophage infiltration. We found that T-lymphocytes and FOXP3+ infiltrates in primary tumours positively correlated with that of metastatic lesions (ρ = 0.512, P = 0.038 and ρ = 0.698, P = 0.007, respectively), while a strong trend existed for CD204+ infiltrates (ρ = 0.404, P = 0.087). We also observed T- and B-lymphocytes, and CD204+ macrophages to be significantly higher in a dog's pulmonary metastasis compared to their primary tumour (P = 0.018, P = 0.018, P = 0.016, respectively), while FOXP3+ cells were only significantly higher in metastases when all primary tumour and metastasis lesions were compared without pairing (P = 0.036). Together, these findings suggest that the metastatic immune microenvironment may be influenced by that of the primary cOSA, and that primary tumour immune biomarkers could potentially be applied to predict immunotherapeutic responses in gross metastatic disease. We, therefore, provide a rationale for the treatment of cOSA pulmonary metastases with immunotherapeutics that enhance the anti-tumour activity of these immune cells, particularly in dogs with moderate to high immune cell infiltration in their primary tumours.

AB - Our lack of understanding of the immune microenvironment in canine osteosarcoma (cOSA) has limited the identification of potential immunotherapeutic targets. In particular, our ability to utilize readily available tissue from a dog's primary tumour to predict the type and extent of immune response in their pulmonary metastatic lesions is unknown. We, therefore, collected 21 matched pairs of primary tumours and pulmonary metastatic lesions from dogs with OSA and performed immunohistochemistry to quantify T-lymphocyte (CD3), FOXP3+ cell, B-lymphocyte (Pax-5), and CD204+ macrophage infiltration. We found that T-lymphocytes and FOXP3+ infiltrates in primary tumours positively correlated with that of metastatic lesions (ρ = 0.512, P = 0.038 and ρ = 0.698, P = 0.007, respectively), while a strong trend existed for CD204+ infiltrates (ρ = 0.404, P = 0.087). We also observed T- and B-lymphocytes, and CD204+ macrophages to be significantly higher in a dog's pulmonary metastasis compared to their primary tumour (P = 0.018, P = 0.018, P = 0.016, respectively), while FOXP3+ cells were only significantly higher in metastases when all primary tumour and metastasis lesions were compared without pairing (P = 0.036). Together, these findings suggest that the metastatic immune microenvironment may be influenced by that of the primary cOSA, and that primary tumour immune biomarkers could potentially be applied to predict immunotherapeutic responses in gross metastatic disease. We, therefore, provide a rationale for the treatment of cOSA pulmonary metastases with immunotherapeutics that enhance the anti-tumour activity of these immune cells, particularly in dogs with moderate to high immune cell infiltration in their primary tumours.

KW - dogs

KW - immunotherapy

KW - neoplasm metastasis

KW - osteosarcoma

KW - tumour microenvironment

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U2 - 10.1111/vco.12459

DO - 10.1111/vco.12459

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JO - Veterinary and Comparative Oncology

JF - Veterinary and Comparative Oncology

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