Increased monocyte chemotactic protein‐1 concentration and monocyte count independently associate with a poor prognosis in dogs with lymphoma

Abstract

Overexpression of the chemokine monocyte chemotactic protein-1 (MCP-1) has been associated with a poor prognosis in many human cancers. Increased MCP-1 concentrations may promote tumour progression by increasing mobilization of myeloid derived suppressor cells such as immature monocytes and neutrophils. We hypothesized that increased numbers of peripheral neutrophils or monocytes and increased MCP-1 concentrations would predict a worse outcome in dogs with multicentric lymphoma. In this retrospective study involving 26 client-owned dogs diagnosed with lymphoma, we show that peripheral neutrophil and monocyte counts as well as serum MCP-1 concentrations were significantly elevated relative to healthy control animals, and that such increases were associated with a decreased disease-free interval in dogs treated with chemotherapy based on cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP). To our knowledge, this is the first study showing that pretreatment evaluation of monocyte and neutrophil counts can provide important prognostic information in dogs with lymphoma. The mechanisms underlying these observations remain to be determined.

Suppression of canine myeloid cells by soluble factors from cultured canine tumor cells

“…Both innate and adaptive immune cells can be altered during cancer and the contribution of dysregulated myeloid cells is increasingly being recognized in humans and mice with cancer (Mantovani et al, 2010; Schmid and Varner, 2010; Yang and Carbone, 2004). This study showed that canine tumor cells affect canine myeloid cell function, which may explain the findings that increased myeloid cells or myeloid cell markers are negative prognostic indicators (Perry et al, 2011; Sottnik et al, 2010). It is possible that these dogs with cancer were less able to generate anti-tumor immunity, even in the presence of elevated myeloid cell numbers, due to suppressive or dysfunctional myeloid cells.…”

“…Recent work in dogs suggests that peripheral blood myeloid cell populations (e.g. monocytes and neutrophils) may be a prognostic indicator in canine cancer and that canine myeloid cells may be useful for canine cancer vaccines but, at present, the effects of cancer on canine myeloid cell responses has not been studied (Bird et al, 2008; Perry et al, 2011; Sottnik et al, 2010). …”

Dissecting the Regulatory Microenvironment of a Large Animal Model of Non-Hodgkin Lymphoma: Evidence of a Negative Prognostic Impact of FOXP3+ T Cells in Canine B Cell Lymphoma

“…Prognostic factors in other canine studies of multicentric lymphoma have included sex [78], [79], B or T immunophenotype [53], [80]–[82], stage [81], [83]–[85], substage [79], [83], serum calcium concentration [86], packed cell volume [87], monocyte concentration [88], prior administration of corticosteroids [89], [90], treatment protocol [62], [91], coagulation profile [92], presence of minimal residual disease after treatment [93], and cytomorphological and histopathological characteristics [56], [61], [62], [81]. However, in common with our own observations, different studies have yielded different conclusions and have not all been able to demonstrate a prognostic impact of every one of the examined variables: factors such as the number and clinical heterogeneity of recruited patients and the nature of the specific end points examined influence the results of such outcome analyses [94].…”

Monocyte Chemoattractant Protein-1 in Dogs Affected with Neoplasia or Inflammation

“…In another study, elevated serum MCP-1 concentrations were associated with decreased disease-free intervals in lymphoma dogs treated by chemotherapy [12]. These reports suggest that MCP-1 may be available as prognostic indicators of IMHA and lymphoma in dogs, moreover, this may be true of some other diseases.…”