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单独接受实验性免疫疗法或实验性免疫疗法加小剂量节拍化疗治疗的犬口腔黑色素瘤患者中全身炎症和免疫指标与生存的关联

Association of Systemic Inflammatory and Immune Indices With Survival in Canine Patients With Oral Melanoma, Treated With Experimental Immunotherapy Alone or Experimental Immunotherapy Plus Metronomic Chemotherapy.

作者信息

Garcia Jéssica Soares, Nowosh Victor, López Rossana Verónica Mendoza, Massoco Cristina de Oliveira

机构信息

Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.

Center for Translational Research in Oncology of the Institute of Cancer of São Paulo State, São Paulo, Brazil.

出版信息

Front Vet Sci. 2022 Jul 6;9:888411. doi: 10.3389/fvets.2022.888411. eCollection 2022.

DOI:10.3389/fvets.2022.888411
PMID:35873678
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9296851/
Abstract

Analysis of the expression of inflammatory markers before starting treatment in human patients with cancer helps to predict outcomes and prognosis; however, there have been few studies on this topic in veterinary medicine. The present study aimed to evaluate inflammatory indices before treatment with autologous antitumor vaccine alone or this vaccine plus metronomic chemotherapy (MC) to predict response and prognosis. The indices included the neutrophil-lymphocyte ratio (NRL), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), C-reactive-protein-albumin ratio (CRP/ALB), lactate dehydrogenase level (LDH), frequency of blood lymphocyte subsets (CD4, CD8, Treg, and CD4/CD8 ratio) and frequency of blood myeloid-derived suppressor cells (MDSCs: monocytic [M]- MDSCs, and granulocytic [PMN]-MDSCs). Blood samples were collected from 25 dogs with oral melanoma treated with the autologous antitumor vaccine and from nine dogs that received MC plus vaccine before surgery. There were no statistically significant differences in the progression-free survival (PFS) or overall survival (OS) between the groups. In addition to the clinical stage, the CRP/ALB ratio and blood circulating Tregs in the univariate analysis showed an association with PFS and OS, and thus were selected for multivariable analysis. The CRP/ALB ratio was associated with PFS [hazard ratio (HR), 1.1; 95% confidence interval (CI), 1.0-1.1; = 0.017] and OS [HR, 1; 95%CI, 1.0-1.1; = 0.023]. Similarly, Treg was associated with PFS (HR, 1.6; 95% CI, 1.2-2.1; = 0.001) and OS (HR, 1.6; 95% CI, 1.2-2.1; = 0.001). Furthermore, canine patients with a CRP/ALB ratio above the cut-off point of 1.9 (established by receiver operating characteristic curve analysis) had worse PFS and OS, indicating the impact of the preoperative CRP/ALB ratio on the PFS and OS of dogs with oral melanoma. The CRP/ALB ratio and frequency of circulating Tregs are potential prognostic markers in dogs with oral melanoma.

摘要

分析癌症患者在开始治疗前炎症标志物的表达有助于预测治疗结果和预后;然而,兽医医学中关于这一主题的研究很少。本研究旨在评估单独使用自体抗肿瘤疫苗或该疫苗联合节拍化疗(MC)治疗前的炎症指标,以预测反应和预后。这些指标包括中性粒细胞与淋巴细胞比值(NRL)、血小板与淋巴细胞比值(PLR)、单核细胞与淋巴细胞比值(MLR)、全身免疫炎症指数(SII)、C反应蛋白与白蛋白比值(CRP/ALB)、乳酸脱氢酶水平(LDH)、血液淋巴细胞亚群频率(CD4、CD8、调节性T细胞及CD4/CD8比值)以及血液髓源性抑制细胞频率(MDSCs:单核细胞型[M]-MDSCs和粒细胞型[PMN]-MDSCs)。采集了25只接受自体抗肿瘤疫苗治疗的口腔黑色素瘤犬以及9只术前接受MC联合疫苗治疗的犬的血样。两组之间的无进展生存期(PFS)或总生存期(OS)无统计学显著差异。在单变量分析中,除临床分期外,CRP/ALB比值和血液中循环调节性T细胞与PFS和OS相关,因此被选入多变量分析。CRP/ALB比值与PFS相关[风险比(HR),1.1;95%置信区间(CI),1.0 - 1.1;P = 0.017],与OS相关[HR,1;95%CI,1.0 - 1.1;P = 0.023]。同样,调节性T细胞与PFS相关(HR,1.6;95%CI,1.2 - 2.1;P = 0.001),与OS相关(HR,1.6;95%CI,1.2 - 2.1;P = 0.001)。此外,CRP/ALB比值高于通过受试者工作特征曲线分析确定的截断点1.9的犬类患者,其PFS和OS较差,这表明术前CRP/ALB比值对口腔黑色素瘤犬的PFS和OS有影响。CRP/ALB比值和循环调节性T细胞频率是口腔黑色素瘤犬潜在的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/391c/9296851/c8cd71cf1252/fvets-09-888411-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/391c/9296851/f638e4167bcd/fvets-09-888411-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/391c/9296851/5a5c10ea36e1/fvets-09-888411-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/391c/9296851/c8cd71cf1252/fvets-09-888411-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/391c/9296851/f638e4167bcd/fvets-09-888411-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/391c/9296851/5a5c10ea36e1/fvets-09-888411-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/391c/9296851/c8cd71cf1252/fvets-09-888411-g0003.jpg

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