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肿瘤浸润淋巴细胞在不同犬软组织肉瘤组织学类型中存在差异。

Tumor-infiltrating lymphocytes vary in different canine soft tissue sarcoma histological types.

作者信息

Avallone Giancarlo, Brigandì Elena, Tugnoli Chiara, Rigillo Antonella, Bacci Barbara, Roccabianca Paola

机构信息

University of Bologna, Bologna, Italy.

i-Vet, Flero, Italy.

出版信息

Vet Pathol. 2025 May;62(3):276-283. doi: 10.1177/03009858241300556. Epub 2024 Dec 9.

DOI:10.1177/03009858241300556
PMID:39651618
Abstract

Soft tissue sarcomas (STSs) are conventionally viewed as poorly immunogenic tumors; however, some human STSs have recently been reported to elicit an immune response, thus representing potential candidates for immunotherapy. Data regarding immune cell infiltrates in canine STSs are limited and reported without tumor-type stratification. The aim of this study was to retrospectively assess tumor-infiltrating lymphocytes (TILs) in canine STSs of 5 different histotypes. Eighty-seven canine STSs were collected: 22 perivascular wall tumors (PWTs), 19 liposarcomas, 17 fibrosarcomas, 16 myxosarcomas, and 13 leiomyosarcomas. The tumors were graded and immunolabeled for CD3, CD20, and FoxP3, and slides were scanned. T-cell, B-cell, Treg, and total TIL densities were quantified with QuPath software and expressed as cells/mm. The B/T-cells ratio and Treg/T-cell proportions were calculated. Total TIL densities were higher in PWTs and myxosarcomas (median = 225 and 303, respectively). PWTs had higher T-cell density but lower Treg proportion (median = 152 and 7.6% respectively). Myxosarcomas had higher Treg densities and B/T-cell ratios (median = 24.4 and 1.57, respectively). No association with grade was found among STSs as a group. In myxosarcomas, higher grade was significantly associated with higher total TILs, and CD20+ and FoxP3+ cell densities ( < .05). The results suggest that PWTs and myxosarcomas may represent the most immunogenic STS types. Myxosarcomas elicit a B-cell and Treg-rich immune response; PWTs stimulate a T-cell-rich and Treg-poor reaction. The immune system response may contribute to the more aggressive behavior of myxosarcomas and the more indolent course of PWTs.

摘要

软组织肉瘤(STSs)传统上被视为免疫原性较差的肿瘤;然而,最近有报道称一些人类STSs会引发免疫反应,因此成为免疫治疗的潜在候选对象。关于犬类STSs中免疫细胞浸润的数据有限,且未按肿瘤类型分层报告。本研究的目的是回顾性评估5种不同组织学类型的犬类STSs中的肿瘤浸润淋巴细胞(TILs)。收集了87例犬类STSs:22例血管周围壁肿瘤(PWTs)、19例脂肪肉瘤、17例纤维肉瘤、16例黏液肉瘤和13例平滑肌肉瘤。对肿瘤进行分级,并对CD3、CD20和FoxP3进行免疫标记,然后扫描切片。使用QuPath软件对T细胞、B细胞、调节性T细胞(Treg)和总TIL密度进行定量,并表示为细胞/mm。计算B/T细胞比率和Treg/T细胞比例。PWTs和黏液肉瘤中的总TIL密度较高(中位数分别为225和303)。PWTs的T细胞密度较高,但Treg比例较低(中位数分别为152和7.6%)。黏液肉瘤的Treg密度和B/T细胞比率较高(中位数分别为24.4和1.57)。作为一个整体,在STSs中未发现与分级相关。在黏液肉瘤中,较高的分级与较高的总TILs以及CD20+和FoxP3+细胞密度显著相关(P <.05)。结果表明,PWTs和黏液肉瘤可能是免疫原性最强的STSs类型。黏液肉瘤引发富含B细胞和Treg的免疫反应;PWTs刺激富含T细胞且Treg较少的反应。免疫系统反应可能导致黏液肉瘤的行为更具侵袭性,而PWTs的病程更惰性。

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