Immunophenotypic features of tumor infiltrating lymphocytes from mammary carcinomas in female dogs associated with prognostic factors and survival rates
Immunophenotypic features of tumor infiltrating lymphocytes from mammary carcinomas in female dogs associated with prognostic factors and survival rates
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DOI：
10.1186/1471-2407-10-256
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发表时间：
2010-06-04
期刊：
影响因子：
3.8
通讯作者：
Cassali, Geovanni D.
中科院分区：
文献类型：
--
作者：
Estrela-Lima, Alessandra;Araujo, Marcio S. S.;Cassali, Geovanni D.
背景：肿瘤发生发展过程中，免疫系统在多因子生物系统中起着重要作用。然而，炎症反应在促进/控制恶性细胞中的作用仍然存在争议，并且对细胞亚群及其机制的研究很少。本研究的目的是研究犬乳腺癌的临床病理状态和肿瘤浸润淋巴细胞的免疫表型特征及其与动物存活率的关系。方法：对51只乳腺癌动物进行系统的临床病理分析（肿瘤大小、有无淋巴结及肺转移、临床分期、组织学分级、炎症分布及强度、淋巴细胞浸润强度）及生存率，并将其分类为混合性肿瘤- mc - bmt = 31和癌- mc = 20。选取24只动物（MC- bmt = 16, MC = 8）进行流式细胞术免疫表型研究。结果：数据分析显示，与MC相比，MC- bmt中临床分期II-IV期和组织学分级I的发生率更高。单因素分析显示，炎症强度（中度/强烈）和CD4(+) （bb0 = 66.7%）或CD8(+) t细胞比例（< 33.3%）与生存率差无关。多因素分析显示，只有淋巴细胞浸润强度>= 600 （P = 0.02）仍然是独立的预后因素。尽管有临床表现，但淋巴细胞是肿瘤浸润的主要细胞类型。未发生转移的MC-BMT患者t细胞百分比较高，发生转移的MC-BMT患者b淋巴细胞百分比较高（P < 0.05）。CD4(+) t细胞的相对比例在转移瘤（MC- bmt和MC）中显著高于（P < 0.05），而CD8(+) t细胞的比例在未转移的MC- bmt中较高。因此，CD4(+)/CD8（+）比值在两组转移中均显著升高。无论肿瘤类型如何，CD4(+) t细胞比例高而CD8(+) t细胞比例低的动物存活率降低。结论：淋巴细胞浸润的强度和CD4（+）和CD8(+) t淋巴细胞的相对丰度可能是犬乳腺癌生存预后的重要生物标志物。
Background: The immune system plays an important role in the multifactorial biologic system during the development of neoplasias. However, the involvement of the inflammatory response in the promotion/control of malignant cells is still controversial, and the cell subsets and the mechanisms involved are poorly investigated. The goal of this study was to characterize the clinical-pathological status and the immunophenotyping profile of tumor infiltrating lymphocytes and their association with the animal survival rates in canine mammary carcinomas.Methods: Fifty-one animals with mammary carcinomas, classified as carcinomas in mixed tumors-MC-BMT = 31 and carcinomas-MC = 20 were submitted to systematic clinical-pathological analysis (tumor size; presence of lymph node and pulmonary metastasis; clinical stage; histological grade; inflammatory distribution and intensity as well as the lymphocytic infiltrate intensity) and survival rates. Twenty-four animals (MC-BMT = 16 and MC = 8) were elected to the immunophenotypic study performed by flow cytometry.Results: Data analysis demonstrated that clinical stage II-IV and histological grade was I more frequent in MC-BMT as compared to MC. Univariate analysis demonstrated that the intensity of inflammation (moderate/intense) and the proportion of CD4(+) (>= 66.7%) or CD8(+) T-cells (< 33.3%) were not associated with worse survival rate. Multivariate analysis demonstrated that only lymphocytic infiltrate intensity >= 600 (P = 0.02) remained as independent prognostic factor. Despite the clinical manifestation, the lymphocytes represented the predominant cell type in the tumor infiltrate. The percentage of T-cells was higher in animals with MC-BMT without metastasis, while the percentage of B-lymphocytes was greater in animals with metastasized MC-BMT (P < 0.05). The relative percentage of CD4(+) T-cells was significantly greater in metastasized tumors (both MC-BMT and MC), (P < 0.05) while the proportion of CD8(+) T-cells was higher in MC-BMT without metastasis. Consequently, the CD4(+)/CD8(+) ratio was significantly increased in both groups with metastasis. Regardless of the tumor type, the animals with high proportions of CD4(+) and low CD8(+) T-cells had decreased survival rates.Conclusion: The intensity of lymphocytic infiltrate and probably the relative abundance of the CD4(+) and CD8(+) T-lymphocytes may represent important survival prognostic biomarkers for canine mammary carcinomas.