In human medicine, there is a growing body of evidence that tumor cells are able to escape T-cell mediated anti-tumor immunity . Therefore, immunotherapy represents the new frontier of cancer treatment  and clinical trials with customized cancer vaccines are ongoing . Dogs with diffuse large B-cell lymphoma (DLBCL) benefit from the inclusion of immunotherapy in the treatment regimen . However, the immunity status of dogs affected by DLBCL has been scarcely characterized. The aim of this study was to describe the composition of the intra-tumoral non-neoplastic lymphoid population in lymph node aspirates of dogs with DLBCL, and to assess the possible prognostic role of different immune patterns. Twenty-three cases with histopathological diagnosis of DLBCL were retrospectively extracted from the flow cytometric (FC) database of the Department of Veterinary Medicine (University of Milan). All cases were obtained from a single oncological referral center (Centro Oncologico Veterinario), underwent a standardized complete staging workup and received chemo-immunotherapy. The percentage of CD21+, CD5+, CD4+ and CD8+ cells out of small non-neoplastic lymphocytes was extracted from FC data. Hierarchical cluster analysis separated two groups: group 1 (12 dogs) had a lower percentage of small cells and most of them were CD21+; group 2 (11 dogs) had significantly higher percentage of small cells and most of them were CD5+, either CD4+ or CD8+. CD5/CD21 ratio accurately discriminated between the two groups, with a cutoff value of 1.0 having 100% sensitivity and specificity. Breed, sex, age, anemia, thrombocytopenia, LDH levels, disease stage and achievement of complete remission (CR) were equally represented among groups, whereas all symptomatic dogs (n=5) were in group 1. The achievement of CR was the only variable significantly influencing lymphoma-specific survival (LSS). Still, dogs in group 1 had a shorter LSS compared to dogs in group 2 (median 148 days and 623 days, respectively) (p=0.187). Based on our results, about a half of dogs with DLBCL showed a poor number of T-cell infiltrating the tumor. This was associated with uneffective response to immunotherapy, as median LSS was similar to that obtained in dogs treated with chemotherapy and placebo in a previous clinical trial . Although preliminar, our data suggest that a higher component of intraneoplastic T-cells predict a good response to immunotherapy. Further studies are needed to assess the activation status of T-cells in these dogs and the strategies used by the neoplastic cells to escape immune surveillance. A better characterization of these population in DLBCL before treatment will help to stratify dogs and drive therapy, eventually.  Curran EK et al. Mechanisms of immune tolerance in leukemia and lymphoma, Trends in immunology, 38(7):513-525, 2017.  Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade, Science, 359(6382):1350-1355, 2018.  Sahin U, Tureci O. Personalized vaccines for cancer immunotherapy, Science, 359(6382):1355-1360, 2018.  Marconato L et al. Randomized, placebo-controlled, double-blinded chemoimmunotherapy clinical trial in a pet dog model of diffuse large B-cell lymphoma, Clinical Cancer Research, 20(3):668-677, 2014.  Barber LG, Weishaar KM. Criteria for designation of clinical substage in canine lymphoma: a survey of veterinary oncologists, Veterinary and Comparative Oncology, 14 Suppl 1:32-39, 2016.
Prognostic significance and possible therapeutic implications of tumor-infiltrating lymphocytes in de novo canine diffuse large b-cell lymphoma / V. Martini, L. Aresu, L. Marconato, M. Cozzi, S. Bernardi, S. Comazzi. ((Intervento presentato al 72. convegno Convegno SISVet tenutosi a Torino nel 2018.
|Titolo:||Prognostic significance and possible therapeutic implications of tumor-infiltrating lymphocytes in de novo canine diffuse large b-cell lymphoma|
|Data di pubblicazione:||2018|
|Settore Scientifico Disciplinare:||Settore VET/03 - Patologia Generale e Anatomia Patologica Veterinaria|
|Enti collegati al convegno:||Società Italaina delle Scienze Veterinarie|
|Citazione:||Prognostic significance and possible therapeutic implications of tumor-infiltrating lymphocytes in de novo canine diffuse large b-cell lymphoma / V. Martini, L. Aresu, L. Marconato, M. Cozzi, S. Bernardi, S. Comazzi. ((Intervento presentato al 72. convegno Convegno SISVet tenutosi a Torino nel 2018.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|