Association of macrophage and lymphocyte infiltration with outcome in canine osteosarcoma

Sita S. Withers, Katherine A Skorupski, Daniel York, Jin W. Choi, Kevin D Woolard, Renee Laufer-Amorim, Ellen E. Sparger, Carlos O. Rodriguez, Stephen J Mcsorley, Arta M Monjazeb, William J Murphy, Robert J Canter, Robert B Rebhun

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3 Citations (Scopus)

Abstract

Immunotherapeutic strategies have shown promise for the treatment of canine osteosarcoma (cOSA). Very little is known about the immune microenvironment within cOSA, however, limiting our ability to identify potential immune targets and biomarkers of therapeutic response. We therefore prospectively assessed the disease-free interval (DFI) and overall survival time (ST) of 30 dogs with cOSA treated with amputation and six doses of adjuvant carboplatin. We then quantified lymphocytic (CD3+, FOXP3+) and macrophage (CD204+) infiltrates within the primary tumours of this cohort using immunohistochemistry, and evaluated their association with outcome. Overall, the median DFI and ST were 392 and 455 days, respectively. The median number of CD3+ and FOXP3+ infiltrates were 45.8 cells/mm2 (4.6-607.6 cells/mm2) and 8.5 mm2 (0-163.1 cells/mm2), respectively. The median area of CD204+ macrophages was 4.7% (1.3%-23.3%), and dogs with tumours containing greater than 4.7% CD204+ macrophages experienced a significantly longer DFI (P = 0.016). Interestingly, a significantly lower percentage of CD204+ macrophages was detected in cOSA arising from the proximal humerus compared to other appendicular bone locations (P = 0.016). Lymphocytic infiltrates did not appear to correlate with outcome in cOSA. Overall, our findings suggest that macrophages may play a role in inhibiting cOSA progression, as has been suggested in human osteosarcoma.

Original languageEnglish (US)
JournalVeterinary and Comparative Oncology
DOIs
StateAccepted/In press - Jan 1 2018

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osteosarcoma
Osteosarcoma
Canidae
macrophages
lymphocytes
Macrophages
Lymphocytes
dogs
Dogs
Carboplatin
Humerus
neoplasms
amputation
humerus
Amputation
cells
Disease-Free Survival
Neoplasms
adjuvants
immunohistochemistry

Keywords

  • dogs
  • immunotherapy
  • macrophages
  • osteosarcoma
  • tumour microenvironment

ASJC Scopus subject areas

  • veterinary(all)

Cite this

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title = "Association of macrophage and lymphocyte infiltration with outcome in canine osteosarcoma",
abstract = "Immunotherapeutic strategies have shown promise for the treatment of canine osteosarcoma (cOSA). Very little is known about the immune microenvironment within cOSA, however, limiting our ability to identify potential immune targets and biomarkers of therapeutic response. We therefore prospectively assessed the disease-free interval (DFI) and overall survival time (ST) of 30 dogs with cOSA treated with amputation and six doses of adjuvant carboplatin. We then quantified lymphocytic (CD3+, FOXP3+) and macrophage (CD204+) infiltrates within the primary tumours of this cohort using immunohistochemistry, and evaluated their association with outcome. Overall, the median DFI and ST were 392 and 455 days, respectively. The median number of CD3+ and FOXP3+ infiltrates were 45.8 cells/mm2 (4.6-607.6 cells/mm2) and 8.5 mm2 (0-163.1 cells/mm2), respectively. The median area of CD204+ macrophages was 4.7{\%} (1.3{\%}-23.3{\%}), and dogs with tumours containing greater than 4.7{\%} CD204+ macrophages experienced a significantly longer DFI (P = 0.016). Interestingly, a significantly lower percentage of CD204+ macrophages was detected in cOSA arising from the proximal humerus compared to other appendicular bone locations (P = 0.016). Lymphocytic infiltrates did not appear to correlate with outcome in cOSA. Overall, our findings suggest that macrophages may play a role in inhibiting cOSA progression, as has been suggested in human osteosarcoma.",
keywords = "dogs, immunotherapy, macrophages, osteosarcoma, tumour microenvironment",
author = "Withers, {Sita S.} and Skorupski, {Katherine A} and Daniel York and Choi, {Jin W.} and Woolard, {Kevin D} and Renee Laufer-Amorim and Sparger, {Ellen E.} and Rodriguez, {Carlos O.} and Mcsorley, {Stephen J} and Monjazeb, {Arta M} and Murphy, {William J} and Canter, {Robert J} and Rebhun, {Robert B}",
year = "2018",
month = "1",
day = "1",
doi = "10.1111/vco.12444",
language = "English (US)",
journal = "Veterinary and Comparative Oncology",
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TY - JOUR

T1 - Association of macrophage and lymphocyte infiltration with outcome in canine osteosarcoma

AU - Withers, Sita S.

AU - Skorupski, Katherine A

AU - York, Daniel

AU - Choi, Jin W.

AU - Woolard, Kevin D

AU - Laufer-Amorim, Renee

AU - Sparger, Ellen E.

AU - Rodriguez, Carlos O.

AU - Mcsorley, Stephen J

AU - Monjazeb, Arta M

AU - Murphy, William J

AU - Canter, Robert J

AU - Rebhun, Robert B

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Immunotherapeutic strategies have shown promise for the treatment of canine osteosarcoma (cOSA). Very little is known about the immune microenvironment within cOSA, however, limiting our ability to identify potential immune targets and biomarkers of therapeutic response. We therefore prospectively assessed the disease-free interval (DFI) and overall survival time (ST) of 30 dogs with cOSA treated with amputation and six doses of adjuvant carboplatin. We then quantified lymphocytic (CD3+, FOXP3+) and macrophage (CD204+) infiltrates within the primary tumours of this cohort using immunohistochemistry, and evaluated their association with outcome. Overall, the median DFI and ST were 392 and 455 days, respectively. The median number of CD3+ and FOXP3+ infiltrates were 45.8 cells/mm2 (4.6-607.6 cells/mm2) and 8.5 mm2 (0-163.1 cells/mm2), respectively. The median area of CD204+ macrophages was 4.7% (1.3%-23.3%), and dogs with tumours containing greater than 4.7% CD204+ macrophages experienced a significantly longer DFI (P = 0.016). Interestingly, a significantly lower percentage of CD204+ macrophages was detected in cOSA arising from the proximal humerus compared to other appendicular bone locations (P = 0.016). Lymphocytic infiltrates did not appear to correlate with outcome in cOSA. Overall, our findings suggest that macrophages may play a role in inhibiting cOSA progression, as has been suggested in human osteosarcoma.

AB - Immunotherapeutic strategies have shown promise for the treatment of canine osteosarcoma (cOSA). Very little is known about the immune microenvironment within cOSA, however, limiting our ability to identify potential immune targets and biomarkers of therapeutic response. We therefore prospectively assessed the disease-free interval (DFI) and overall survival time (ST) of 30 dogs with cOSA treated with amputation and six doses of adjuvant carboplatin. We then quantified lymphocytic (CD3+, FOXP3+) and macrophage (CD204+) infiltrates within the primary tumours of this cohort using immunohistochemistry, and evaluated their association with outcome. Overall, the median DFI and ST were 392 and 455 days, respectively. The median number of CD3+ and FOXP3+ infiltrates were 45.8 cells/mm2 (4.6-607.6 cells/mm2) and 8.5 mm2 (0-163.1 cells/mm2), respectively. The median area of CD204+ macrophages was 4.7% (1.3%-23.3%), and dogs with tumours containing greater than 4.7% CD204+ macrophages experienced a significantly longer DFI (P = 0.016). Interestingly, a significantly lower percentage of CD204+ macrophages was detected in cOSA arising from the proximal humerus compared to other appendicular bone locations (P = 0.016). Lymphocytic infiltrates did not appear to correlate with outcome in cOSA. Overall, our findings suggest that macrophages may play a role in inhibiting cOSA progression, as has been suggested in human osteosarcoma.

KW - dogs

KW - immunotherapy

KW - macrophages

KW - osteosarcoma

KW - tumour microenvironment

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U2 - 10.1111/vco.12444

DO - 10.1111/vco.12444

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JO - Veterinary and Comparative Oncology

JF - Veterinary and Comparative Oncology

SN - 1476-5829

ER -