Increased tumor-infiltrating lymphocyte density is associated with favorable outcomes in a comparative study of canine histiocytic sarcoma.

Autor: Lenz JA; Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA. jlenz@upenn.edu., Assenmacher CA; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Costa V; Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA., Louka K; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Rau S; Metropolitan Veterinary Associates, Norristown, PA, USA., Keuler NS; Department of Statistics, University of Wisconsin-Madison, Madison, WI, USA., Zhang PJ; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Maki RG; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Durham AC; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Radaelli E; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Atherton MJ; Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA. mattath@upenn.edu.; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA. mattath@upenn.edu.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2022 Apr; Vol. 71 (4), pp. 807-818. Date of Electronic Publication: 2021 Aug 20.
DOI: 10.1007/s00262-021-03033-z
Abstrakt: 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.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: