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肿瘤浸润的 CD4 和 CD8 淋巴细胞和巨噬细胞与三阴性犬乳腺复合体癌的预后因素有关。

Tumor-infiltrating CD4 and CD8 lymphocytes and macrophages are associated with prognostic factors in triple-negative canine mammary complex type carcinoma.

机构信息

Department of Veterinary Surgery and Anesthesiology, School of Veterinary Medicine and Animal Science São Paulo State University - UNESP, Botucatu, SP, Brazil.

Superintendencia Unidade Hospitalar Veterinaria Universitaria, Federal University of the Fronteira Sul, Realeza, Brazil.

出版信息

Res Vet Sci. 2019 Oct;126:29-36. doi: 10.1016/j.rvsc.2019.08.021. Epub 2019 Aug 13.

Abstract

This study aimed to evaluate the association of CD3, CD4, and CD8 T cells and tumor-infiltrating macrophages (TIMs) with the clinical parameters of female dogs harboring mammary gland tumors. Thirty female dogs affected with mammary carcinomas were used, and all tumors were histologically classified as complex carcinoma and were triple-negative phenotype determined by immunohistochemistry. Freshly frozen sections were used to determine CD3, CD4 and CD8 T cells by immunohistochemistry, and TIMs were determined by immunofluorescence assays. Ten out of the 30 dogs showed lymph node metastasis at diagnosis. Fifteen dogs had a tumor of grade I (15/30), nine (9/30) had a tumor of grade II and six (6/30) had a tumor of grade III. The mean overall survival was 680.5 days (± 200.4). Dogs with sentinel lymph node positivity (10/30) (P = .0035) and dogs that developed metastasis (P = .0001) showed a shorter survival time. In addition, dogs with a high level of inflammatory infiltrate in tumor tissues presented a shorter survival time (P = .0001) than that of other dogs. Dogs with tumors containing higher numbers of CD3+ T cells (P = .001), CD4+ T cells (P = .001), or TIM cells (P < .0001) showed a shorter survival time than that of other dogs. Our results suggested that characteristics of immune cell infiltrates, including CD3 T cells, CD4 T cells, and TIMs, can be used as potential prognostic indicators for predicting clinical outcomes in dogs with mammary gland tumors, particularly tumors with a complex histological subtype and triple-negative phenotype.

摘要

本研究旨在评估 CD3、CD4 和 CD8 T 细胞和肿瘤浸润巨噬细胞(TIMs)与患有乳腺肿瘤的雌性犬的临床参数之间的关联。使用了 30 只患有乳腺癌的雌性犬,所有肿瘤均通过组织学分类为复杂癌,并通过免疫组织化学确定为三阴性表型。使用新鲜冷冻切片通过免疫组织化学确定 CD3、CD4 和 CD8 T 细胞,并通过免疫荧光测定法确定 TIMs。在诊断时,有 10 只狗出现淋巴结转移。15 只狗的肿瘤为 I 级(15/30),9 只(9/30)为 II 级,6 只(6/30)为 III 级。总的平均存活时间为 680.5 天(±200.4)。前哨淋巴结阳性(10/30)的犬(P=.0035)和发生转移的犬(P=.0001)的存活时间较短。此外,肿瘤组织中炎症浸润程度较高的犬的存活时间较短(P=.0001)。肿瘤中含有更多 CD3+T 细胞(P=.001)、CD4+T 细胞(P=.001)或 TIM 细胞(P<.0001)的犬的存活时间短于其他犬。我们的结果表明,免疫细胞浸润的特征,包括 CD3 T 细胞、CD4 T 细胞和 TIMs,可以作为预测乳腺肿瘤犬临床结局的潜在预后指标,特别是具有复杂组织学亚型和三阴性表型的肿瘤。

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