Comparison of serum cytokine concentrations between healthy dogs and canine osteosarcoma patients at the time of diagnosis

Allende, Carolina; Higgins, B.L.; Johns, Jennifer L.

doi:10.1016/j.vetimm.2020.110084

Cited by 7 publications

(6 citation statements)

References 32 publications

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“…Serum PGE 2 , IL-12p40, IL-8, MCP-1, and SCF concentrations were higher in dogs with OMM than healthy controls, providing clues to the immunological changes associated with tumorigenesis and progression of OMM, including resistance to endogenous antitumor mechanisms. These findings are consistent with previous reports showing elevated serum IL-12p40 in osteosarcoma 42 , IL-8 in mammary tumor and osteosarcoma 42 – 44 , and MCP-1 in lymphoma, histiocytic sarcoma, urothelial carcinoma, and malignant melanoma 45 – 49 compared to healthy dogs. Upregulation of these factors may reflect immunological responses in the tumor microenvironment, but the cellular and locoregional sources of these factors remain to be investigated.…”

Section: Discussionsupporting

confidence: 93%

Exploration of serum biomarkers in dogs with malignant melanoma receiving anti-PD-L1 therapy and potential of COX-2 inhibition for combination therapy

Maekawa

Konnai

Asano

et al. 2022

Sci Rep

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Immune checkpoint inhibitors (ICIs) such as anti-PD-L1 antibodies are widely used to treat human cancers, and growing evidence suggests that ICIs are promising treatments for canine malignancies. However, only some canine oral malignant melanoma (OMM) cases respond to ICIs. To explore biomarkers predictive of survival in dogs with pulmonary metastatic OMM receiving the anti-PD-L1 antibody c4G12 (n = 27), serum concentrations of prostaglandin E2 (PGE2), cytokines, chemokines, and growth factors were measured prior to treatment initiation. Among 12 factors tested, PGE2, interleukin (IL)-12p40, IL-8, monocyte chemotactic protein-1 (MCP-1), and stem cell factor (SCF) were higher in OMM dogs compared to healthy dogs (n = 8). Further, lower baseline serum PGE2, MCP-1, and vascular endothelial growth factor (VEGF)-A concentrations as well as higher IL-2, IL-12, and SCF concentrations predicted prolonged overall survival. These observations suggest that PGE2 confers resistance against anti-PD-L1 therapy through immunosuppression and thus is a candidate target for combination therapy. Indeed, PGE2 suppressed IL-2 and interferon (IFN)-γ production by stimulated canine peripheral blood mononuclear cells (PBMCs), while inhibition of PGE2 biosynthesis using the COX-2 inhibitor meloxicam in combination with c4G12 enhanced Th1 cytokine production by PBMCs. Thus, serum PGE2 may be predictive of c4G12 treatment response, and concomitant use of COX-2 inhibitors may enhance ICI antitumor efficacy.

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Section: Discussionsupporting

confidence: 93%

Exploration of serum biomarkers in dogs with malignant melanoma receiving anti-PD-L1 therapy and potential of COX-2 inhibition for combination therapy

Maekawa

Konnai

Asano

et al. 2022

Sci Rep

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“…Other authors have observed significantly increased serum concentrations of CCL2 in dogs with pulmonary metastatic oral malignant melanoma (Maekawa et al 2022), urothelial carcinoma (Shimizu et al 2019), lymphoma (Perry et al 2011) and histiocytic sarcoma (Nielsen et al 2013). Allende et al (2020) reported an increased serum level of CCL2 in dogs with osteosarcoma; however, a significant difference was not found between the affected dogs and the healthy controls. Moreover, an immunohistochemical study has indicated a significantly higher expression of CCL2 in metastatic canine malignant mammary tumours compared to healthy mammary gland tissue, benign tumours and non-metastatic malignant mammary tumours (Rybicka et al 2016).…”

Section: Discussionmentioning

confidence: 90%

Plasma levels of chemokines CCL2 and CXCL12 in female dogs with malignant mammary gland tumours without and with metastases

Szczubiał,

Łopuszyński,

Dąbrowski

et al. 2023

Polish Journal of Veterinary Sciences

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The aim of this study was to evaluate the plasma levels of chemokines CCL2 and CXCL12 in female dogs with malignant mammary gland tumours without and with metastases. The concentrations of CCL2 and CXCL12 were determined in 25 female dogs with malignant mammary gland tumours (15 without metastases and 10 with metastases) and 10 healthy control animals using a specific canine ELISA assay. The mean plasma concentrations of CCL2 and CXCL12 were significantly higher (p<0.05) in the metastatic group compared to the control group. Moreover, the concentrations of these chemokines were markedly higher in the dogs with metastases than in those without metastases; however, a statistically significant difference was not found. The concentrations of both tested chemokines were numerically increased in the dogs with grade 2 and grade 3 carcinomas compared to the dogs with grade 1 carcinomas but the differences did not reach statistical significance. In conclusion, the results of our study demonstrate that plasma concentrations of chemokines CCL2 and CXCL12 are significantly increased in the dogs with metastatic malignant mammary gland tumours compared to the healthy dogs and show an upward trend compared to those without metastases. However, clarifying whether the increase of these chemokines is a cause or an effect of metastasis in female dogs with malignant mammary gland tumours as well as their potential role in metastatic process requires further research.

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“…In human SLE there are studies suggesting that there is an imbalance between Th1 and Th17 as well as Treg and Th17 response in patients compared to controls 42 , 43 . In canines with osteosarcoma, a previous study has shown increased levels of IL-12/IL-23p40 in serum 44 . NSDTR dogs are at high risk for developing autoimmune disease as well as cancer compared to other breeds, however, the cause of this increased risk remains incompletely known.…”

Section: Introductionmentioning

confidence: 88%

Elevated levels of IL-12/IL-23p40 in Nova Scotia Duck Tolling Retrievers with autoimmune disease and lymphoma

Nilsson,

Kozyrev,

Saellström

et al. 2024

Sci Rep

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The Nova Scotia Duck Tolling Retriever (NSDTR) is predisposed to immune mediated rheumatic disease (IMRD), steroid-responsive meningitis-arteritis (SRMA) and certain forms of cancer. Cytokines are the main regulators of the immune system. Interleukin 2 is a cytokine involved in activation of T regulatory cells, playing a role in central tolerance and tumor immunity. Interleukin 12 and interleukin 23 share the same subunit, p40, and are both pro-inflammatory cytokines. The aim of this study was to compare levels of IL-2 in healthy NSDTRs to those with cancer or autoimmune disease and to compare levels of IL-12/IL-23p40 in healthy NSDTRs and beagles versus NSDTRs with cancer or autoimmune disease. 62 dogs were included in the analysis of IL-12/IL-23p40; healthy NSDTRs (n = 16), healthy beagles (n = 16), NSDTRs autoimmune (n = 18) and NDSTRs lymphoma/mastocytoma (n = 12) and 68 dogs for IL-2; healthy (n = 20), autoimmune (n = 36) and lymphoma/mastocytoma/adenocarcinoma (n = 12). NSDTRs with autoimmune disease had higher levels of IL-12/IL-23p40 compared to healthy dogs (p = 0.008). NSDTRs with lymphoma also had higher levels of IL-12/IL-23p40 compared to healthy NSDTRs (p = 0.002). There was no difference in levels of IL-2 between healthy and diseased NSDTR. Statistical analysis was performed using Bonferroni corrections for multiple testing. These findings can contribute to the knowledge of autoimmune disease and cancer in dogs.

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Comparison of serum cytokine concentrations between healthy dogs and canine osteosarcoma patients at the time of diagnosis

Cited by 7 publications

References 32 publications

Exploration of serum biomarkers in dogs with malignant melanoma receiving anti-PD-L1 therapy and potential of COX-2 inhibition for combination therapy

Exploration of serum biomarkers in dogs with malignant melanoma receiving anti-PD-L1 therapy and potential of COX-2 inhibition for combination therapy

Plasma levels of chemokines CCL2 and CXCL12 in female dogs with malignant mammary gland tumours without and with metastases

Elevated levels of IL-12/IL-23p40 in Nova Scotia Duck Tolling Retrievers with autoimmune disease and lymphoma

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