Tricarico Domenico, Convertino Anna Sara, Mehmeti Irsida, Ranieri Girolamo, Leonetti Francesco, Laface Carmelo, Zizzo Nicola
Department of Pharmacy-Pharmaceutical Sciences, University Aldo Moro, Bari, Italy.
Department of Pharmaceutical Science, Faculty of Pharmacy, "Catholic University Our Lady of Good Counsel", Tirana, Albania.
Front Pharmacol. 2022 Feb 11;13:752098. doi: 10.3389/fphar.2022.752098. eCollection 2022.
Inflammatory cells are emerging markers in various cancers in human trials. The relationship between the inflammatory cells response, cancer grade, and progression has been investigated experimentally in a spontaneous canine model of breast cancer and in the unselected population (18-64 years.o.) under anti-HER2 treatments that represent the most prevalent population in this cancer type. The canine data (N samples = 101) were collected retrospectively for diagnosis in our regional area and evaluated by immunohistochemistry and haemato-chemistry. The inflammatory and immune-related adverse reactions (ADR) in humans were evaluated using EudraVigilance. The "Proportional Reporting Ratio" (PRR) of the mabs was calculated for each ADR with values >2 indicative of high risk. In dogs, we found elevated immunostaining of CD68-macrophages in the lymph node of the aggressive cancer G3 and infiltrating CD20+-lymphocyte. A high density of CD20 + lymphocytes was observed in G1 and a decrease in the density was observed with the histological degree of the tumors. The animals with the sample in G1 showed reduced serum platelet and neutrophil count and elevated lymphocytes and the opposite in severely affected animals. Inflammatory reactions with edema, skin reactions, extravasation, loss of effectiveness, and platelet count decrease (PRR > 13) were found with trastuzumab emtansine in humans, in the absence of immune system reactions. Trastuzumab i.v.-s.c. showed immune system reactions, loss of effectiveness, intolerances with drug withdrawal, technological issues (PRR > 7), and neutrophil count decrease reports. These reactions were less frequently reported for pertuzumab i.v. Case reports of platelet and neutrophil count decrease were not associated with disease progression with a better outcome in humans as in canine breast cancer. Therefore, infiltrating CD68-macrophages are associated with G3, while infiltrating CD20 and elevated serum lymphocytes in parallel with reduced platelet and neutrophil count play a favorable role in human and canine breast cancer.
在人体试验中,炎症细胞正成为各种癌症的新兴标志物。在自发性犬乳腺癌模型以及接受抗HER2治疗的未筛选人群(18 - 64岁)中,已通过实验研究了炎症细胞反应、癌症分级和进展之间的关系,这些人群代表了该癌症类型中最普遍的人群。犬类数据(N样本 = 101)是回顾性收集用于我们地区的诊断,并通过免疫组织化学和血液化学进行评估。使用欧洲药物警戒系统(EudraVigilance)评估人类的炎症和免疫相关不良反应(ADR)。计算每种ADR的单克隆抗体的“比例报告率”(PRR),PRR值>2表明高风险。在犬类中,我们发现侵袭性G3癌症淋巴结中CD68巨噬细胞的免疫染色升高以及浸润性CD20 +淋巴细胞。在G1期观察到高密度的CD20 +淋巴细胞,并且随着肿瘤组织学分级密度降低。G1期有样本的动物血清血小板和中性粒细胞计数降低,淋巴细胞升高,而在严重受影响的动物中则相反。在人类中,曲妥珠单抗偶联物出现了伴有水肿、皮肤反应、外渗、疗效丧失和血小板计数降低(PRR > 13)的炎症反应,且无免疫系统反应。静脉 - 皮下注射曲妥珠单抗出现了免疫系统反应、疗效丧失、停药不耐受、技术问题(PRR > 7)以及中性粒细胞计数降低的报告。静脉注射帕妥珠单抗的这些反应报告较少。血小板和中性粒细胞计数降低的病例报告与疾病进展无关,在人类中结局较好,与犬乳腺癌情况相同。因此,浸润性CD68巨噬细胞与G3相关,而浸润性CD20以及血清淋巴细胞升高同时伴有血小板和中性粒细胞计数降低在人类和犬类乳腺癌中发挥有利作用。