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1.
Cancer Immunol Immunother ; 71(4): 807-818, 2022 Apr.
Article En | MEDLINE | ID: mdl-34415404

Histiocytic sarcoma (HS) is a rare and aggressive tumor in humans with no universally agreed standard of care therapy. Spontaneous canine HS exhibits increased prevalence in specific breeds, shares key genetic and biologic similarities with the human disease, and occurs in an immunocompetent setting. Previous data allude to the immunogenicity of this disease in both species, highlighting the potential for their successful treatment with immunotherapy. Quantification of CD3 tumor-infiltrating lymphocytes (TIL) in five cases of human HS revealed variable intra-tumoral T cell infiltration. Due to the paucity of human cases and lack of current model systems in which to appraise associations between anti-tumor immunity and treatment-outcome in HS, we analyzed clinical data and quantified TIL in 18 dogs that were previously diagnosed with localized HS and treated with curative-intent tumor resection with or without adjuvant chemotherapy. As in humans, assessment of TIL in biopsy tissues taken at diagnosis reveal a spectrum of immunologically "cold" to "hot" tumors. Importantly, we show that increased CD3 and granzyme B TIL are positively associated with favorable outcomes in dogs following surgical resection. NanoString transcriptional analyses revealed increased T cell and antigen presentation transcripts associated with prolonged survival in canine pulmonary HS and a decreased tumor immunogenicity profile associated with shorter survivals in splenic HS. Based on these findings, we propose that spontaneous canine HS is an accessible and powerful novel model to study tumor immunology and will provide a unique platform to preclinically appraise the efficacy and tolerability of anti-cancer immunotherapies for HS.


Dog Diseases , Histiocytic Sarcoma , Animals , Biopsy , Dogs , Histiocytic Sarcoma/genetics , Histiocytic Sarcoma/pathology , Histiocytic Sarcoma/veterinary , Lymphocytes, Tumor-Infiltrating/pathology , Spleen/pathology
2.
J Am Anim Hosp Assoc ; 54(5): 291-295, 2018.
Article En | MEDLINE | ID: mdl-30040443

Feline exocrine pancreatic carcinoma has been reported to be an aggressive tumor with a high metastatic rate and poor prognosis. Studies reporting long-term outcome of cats after surgical removal of solitary pancreatic carcinomas are rare, due to the uncommon diagnosis and paucity of cats who undergo treatment. In this study, nine cases of feline exocrine pancreatic carcinoma from seven academic and private practice veterinary hospitals were reviewed to examine the outcome in cats undergoing surgical removal of the mass. The median postsurgical survival time for the nine cats was 316.5 days (range, 25-964 days), with three cats alive at a median follow-up time of 309 days. This study demonstrates that surgical removal of pancreatic exocrine tumors in cats with localized disease can result in survival times of over 300 days.


Carcinoma/veterinary , Cat Diseases/surgery , Pancreatic Neoplasms/veterinary , Postoperative Complications/veterinary , Animals , Carcinoma/surgery , Cats , Female , Male , Pancreatic Neoplasms/surgery , Retrospective Studies
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