Development of monoclonal antibodies targeting canine PD-L1 and PD-1 and their clinical relevance in Canine Apocrine Gland Anal Sac Adenocarcinoma

Lucia Minoli, Luca Licenziato, Mikolaj Kocikowski, Marzia Cino, Katarzyna Dziubek, Selina Iussich, Antonella Fanelli, Emanuela Morello, Marina Martano, Ted R Hupp, Borek Vojtesek, Maciej Parys, Luca Aresu

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Canine apocrine gland anal sac adenocarcinoma (AGASACA) is an aggressive canine tumor originating from the anal sac glands. Surgical resection, with or without adjuvant chemotherapy, represents the standard of care for this tumor, but the outcome is generally poor particularly for tumors diagnosed at an advanced stage. For this reason, novel treatment options are warranted, and few recent reports suggested an activation of the immune checkpoint axis in canine AGASACA. In our study we developed canine-specific monoclonal antibodies targeting PD-1 and PD-L1. Forty one AGASACAs with complete clinical and follow-up information were then analyzed by immuno histochemistry for the expression of the two checkpoint molecules (PD-L1 and PD-1) and the presence of tumor infiltrating lymphocytes (CD3 and CD20), evaluated within the tumor bulk (intra tumor) and in the surrounding stroma (peritumor). Seventeen AGASACAs (42%) expressed PD-L1 in a range between 5% and 95%. Intratumor lymphocytes were predominantly CD3+ T-cells and positively correlated with the number of PD-1+ intratumor lymphocytes (ρ=0.36; p=0.02). Peritumor lymphocytes were a mixture of CD3+ and CD20+ cells with a variable PD-1 expression (range 0- 50%). PD-L1 expression negatively affected the survival only in the subgroup of dogs treated with surgery alone (n=14; 576 vs 235 days). The presence of a heterogeneous lymphocytic infiltrate and the expression of PD-1 and PD-L1 molecules support the relevance of the immune-microenvironment in canine AGASACAs and the potential value of immune checkpoints as promising therapeutic targets
Original languageEnglish
Article number6188
Issue number24
Early online date14 Dec 2022
Publication statusE-pub ahead of print - 14 Dec 2022

Keywords / Materials (for Non-textual outputs)

  • Dog
  • Apocrine gland anal sac adenocarcinoma
  • PD-1
  • PD-L1
  • Tumor-infiltrating lymphocytes
  • Immunohistochemistry


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