Bacci Barbara, Brunetti Barbara, Maino Cristiano, Martinoli Ginevra, Bacon Nick J, Avallone Giancarlo
Department of Veterinary Medical Sciences, University of Bologna, via Tolara di Sopra 50, 40064 Bologna, Italy.
AURA Veterinary, 70 Priestley Road, Surrey Research Park, Guildford GU2 7AJ, UK.
Animals (Basel). 2024 Dec 20;14(24):3696. doi: 10.3390/ani14243696.
Canine anal sac gland adenocarcinomas (ASACs) are locally aggressive and highly metastatic to regional lymph nodes. Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) can be effective prognostic and predictive markers in numerous human neoplasms and are increasingly investigated in dogs. The aim of this study was to characterize immune cells in canine ASACs and their relationship with tumor size, histologic metastatic status, and tumor clinical stage. Thirty ASACs with known tumor size, metastatic status, and clinical stage were immunolabeled for Iba1 (macrophages), CD20 (B cells), CD3 (T cells), and Foxp3 (regulatory T cells). With image analysis, two areas of 1 mm were analyzed for each case at the tumor core (TC) and invasive margin (IM) and immune cells were counted. Eighteen patients had metastasis at the time of diagnosis, of which fifteen were nodal only, and three were both distant and nodal. The median tumor size was 32.5 mm (range 11-70). The clinical stage was I in five cases, II in seven cases, III in fifteen cases, and IV in three cases. T cells and macrophages were the most abundant immune cells in all tumors. Tumor size did not influence the number or type of infiltrating immune cells. By contrast, significantly higher numbers of TC T lymphocytes were found in patients without metastasis, while significantly higher numbers of TC macrophages were found in dogs with metastasis. Immune cell infiltrate did not differ according to clinical stage. The results indicate that the tumor immune microenvironment, specifically TILs and TAMs, contribute to tumor behavior and may influence metastatic potential; in particular, high CD3 infiltration may prevent tumor progression, while increased macrophage infiltration could promote it.
犬肛门囊腺癌（ASACs）具有局部侵袭性，且极易转移至区域淋巴结。肿瘤浸润淋巴细胞（TILs）和肿瘤相关巨噬细胞（TAMs）在众多人类肿瘤中可作为有效的预后和预测标志物，目前在犬类中也越来越受到研究。本研究的目的是对犬ASACs中的免疫细胞进行特征分析，并探讨它们与肿瘤大小、组织学转移状态及肿瘤临床分期之间的关系。对30例已知肿瘤大小、转移状态和临床分期的ASACs进行免疫标记，检测Iba1（巨噬细胞）、CD20（B细胞）、CD3（T细胞）和Foxp3（调节性T细胞）。通过图像分析，对每个病例在肿瘤核心（TC）和浸润边缘（IM）各分析1平方毫米的两个区域，并对免疫细胞进行计数。18例患者在诊断时已有转移，其中15例仅为淋巴结转移，3例同时伴有远处和淋巴结转移。肿瘤大小中位数为32.5毫米（范围11 - 70毫米）。临床分期为I期的有5例，II期的有7例，III期的有15例，IV期的有3例。T细胞和巨噬细胞是所有肿瘤中最丰富的免疫细胞。肿瘤大小不影响浸润免疫细胞的数量或类型。相比之下，未发生转移的患者肿瘤核心的T淋巴细胞数量显著更高，而发生转移的犬类肿瘤核心的巨噬细胞数量显著更高。免疫细胞浸润情况在不同临床分期之间没有差异。结果表明，肿瘤免疫微环境，特别是TILs和TAMs，对肿瘤行为有影响，并可能影响转移潜能；特别是，高CD3浸润可能阻止肿瘤进展，而巨噬细胞浸润增加则可能促进肿瘤进展。
