Seroprevalence, Clinical, and Pathological Characteristics of Canine Leishmaniasis in a Central Region of Colombia.

INTRODUCTION: Leishmaniasis is a zoonotic disease which is caused by protozoan parasites of the genus Leishmania. Canids are the most important reservoir of the parasites; however, limited data are available on the species of Leishmania prevalent in these animals and their impact on human health. The objective of this study was to estimate the seroprevalence of leishmaniasis in dogs from an inter-Andean region of Colombia during July 2016-July 2017, and to describe the clinical and histopathological features of the disease. MATERIAL AND METHODS: A total of 155 dogs were subjected to clinical examination and a serological test for detection of antibodies against Leishmania. Necropsy was carried out on positive animals and tissue samples were processed by routine histopathology. RESULTS: Altogether 19 dogs were positive in the serological test, establishing a 12% seroprevalence of Leishmania. Clinical examination and necropsy revealed exfoliative and ulcerative dermatitis with haemorrhagic borders on the ears, head, nose, and legs. Histopathology revealed severe multifocal dermatitis with abundant Leishmania amastigotes within the cytoplasm of phagocytic cells, depletion of lymphocytes in lymphoid tissues, interstitial pneumonia, and interstitial nephritis. Tissue samples were positive for Leishmania by PCR. CONCLUSION: The macro- and microscopic changes correlated with the presence of Leishmania as established by serological test and PCR.

Lack of Association Between Epstein-Barr Virus and Mammary Tumours in Dogs.

INTRODUCTION: Epstein-Barr virus (EBV) is a γ-herpesvirus associated with various neoplasms in humans and is a probable aetiological agent in breast cancer; however, a causal relationship has not yet been established. Because of the epidemiological and clinicopathological similarities between breast cancer and canine mammary tumours, dogs have been proposed as a valid model for breast cancer. MATERIAL AND METHODS: A total of 47 canine mammary gland tumour tissues were processed by routine histopathological technique with haematoxylin-eosin staining and classified according to the type of neoplasm. DNA was extracted from paraffin-embedded tissues and the EBNA-1 gene and the BamHI-W region specific for EBV were evaluated by nested PCR. RESULTS: The histopathological evaluation revealed 2 benign neoplasms, and many carcinomas: 2 in situ, 9 simple, 3 solid, 10 complex, and 21 mixed. One sample was positive for the EBNA-1 gene, while all were negative for the BamHI-W region. CONCLUSION: No association was found between EBV and mammary tumours in dogs. However, here we report for the first time the presence of an EBV gene sequence in a canine mammary tumour. It is likely that detection of EBV might be affected by the quality and quantity of DNA extracted from paraffin-embedded tissues. Additional studies are necessary to establish any association of EBV with mammary gland cancer in humans and in dogs, which could eventually lead to better public health prevention and control.

Signal regulatory protein alpha blockade potentiates tumoricidal effects of macrophages on gastroenterological neoplastic cells in syngeneic immunocompetent mice.

AIM: Immunotherapies blocking the CD47-SIRPα pathway by targeting CD47 enhance macrophage phagocytosis of neoplastic cells in mouse models. As SIRPα exhibits relatively restricted tissue expression, SIRPα antagonists may be better tolerated than agents targeting CD47, which is ubiquitously expressed in many tissues. Here, we investigated the therapeutic impact of monoclonal antibodies (mAbs) against CD47 and/or SIRPα on gastroenterological tumors in syngeneic immunocompetent mouse models. METHODS: We used in vitro and in vivo phagocytosis assays in C57BL/6J (B6) mice to investigate anti-CD47/SIRPα mAb effects on Hepa1-6 and CMT93 originating from B6 mice. The influence of these mAbs on macrophage transmigration was also assessed. To investigate anti-SIRPα mAb therapy-induced inhibitory effects on sporadic colon cancer growth, we used a CDX2P9.5-NLS Cre;APC + /FLOX (CPC-APC) mouse model. RESULTS: Systemic anti-SIRPα mAb administration significantly increased Hepa1-6 and CMT93 cell susceptibility to macrophage phagocytosis, both in vitro and in vivo. Conversely, similarly administered anti-CD47 mAb did not promote macrophage phagocytosis of target cells, whereas cells incubated with anti-CD47 mAb prior to inoculation were more susceptible to macrophage phagocytosis. In vitro cell migration assays revealed that binding with anti-CD47 mAb inhibited macrophage transmigration. Anti-SIRPα mAb treatment inhibited tumor progression in CPC-APC mice and significantly improved overall survival. Anti-CD47 mAb administration in vivo eliminated the phagocytosis-promoting CD47 blockade effect, probably by inhibiting macrophage transmigration/chemotaxis. In contrast, anti-SIRPα mAb exhibited enhanced macrophage phagocytic activity and marked anti-tumor effects against gastroenterological malignancies. CONCLUSION: SIRPα mAb augmentation of macrophage phagocytic activity may represent an effective treatment strategy for human gastrointestinal tumors.

Anti-SIRPα antibodies as a potential new tool for cancer immunotherapy.

Tumor cells are thought to evade immune surveillance through interaction with immune cells. Much recent attention has focused on the modification of immune responses as a basis for new cancer treatments. SIRPα is an Ig superfamily protein that inhibits phagocytosis in macrophages upon interaction with its ligand CD47 expressed on the surface of target cells. Here, we show that SIRPα is highly expressed in human renal cell carcinoma and melanoma. Furthermore, an anti-SIRPα Ab that blocks the interaction with CD47 markedly suppressed tumor formation by renal cell carcinoma or melanoma cells in immunocompetent syngeneic mice. This inhibitory effect of the Ab appeared to be mediated by dual mechanisms: direct induction of Ab-dependent cellular phagocytosis of tumor cells by macrophages and blockade of CD47-SIRPα signaling that negatively regulates such phagocytosis. The antitumor effect of the Ab was greatly attenuated by selective depletion not only of macrophages but also of NK cells or CD8+ T cells. In addition, the anti-SIRPα Ab also enhances the inhibitory effects of Abs against CD20 and programmed cell death 1 (PD-1) on tumor formation in mice injected with SIRPα-nonexpressing tumor cells. Anti-SIRPα Abs thus warrant further study as a potential new therapy for a broad range of cancers.