Total and Intratumoral CD8+ T Cell Expressions are Correlated with Miller Payne Grading and WHO Clinical Response of Neoadjuvant Chemotherapy

S. S. Panigoro, S. C. Maulanisa, A. Kurnia, D. Purwanto, P. Rustamadji, H. Herqutanto, F. Sandra
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Abstract

BACKGROUND: Chemotherapy has reported to stimulate immune system through direct activation of cluster of differentiation (CD)8+ T cells. Neoadjuvant chemotherapy (NAC) is known to improve the clinical response of locally advanced breast cancer (LABC) patients. However, the immune response-related factor evaluation of NAC in LABC patients has not been routinely performed. Therefore, current study was conducted to evaluate the correlation of NAC-induced CD8+ T cell with chemotherapy response based on Miller Payne grading and World Health Organization (WHO) criteria.METHODS: LABC patients were recruited and data regarding age, gender, tumor, nodal stages, histopathological grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki67 were obtained. Biopsy and mastectomy tissues were collected and processed for hematoxylin-eosin and CD8 immunohistochemical staining. CD8+ T cell expression in peritumoral and intratumoral areas were documented and measured. Clinical responses based on Miller Payne grading and WHO were analyzed and correlated with CD8+ T cell expression.RESULTS: There were more subjects with high expression of total (80%), intratumoral (82.5%) and peritumoral (65%) CD8+ T cell expressions. The total (p=0.013) and intratumoral (p=0.015) CD8+ T cell expression, but not peritumoral CD8+ T cell expression, were significantly correlated with Miller Payne Grading. The total (p=0.009) and intratumoral (p=0.001) CD8+ T cell expressions were also significantly correlated with WHO clinical response.CONCLUSION: Total and intratumoral CD8+ T cell expressions are correlated with Miller Payne grading and WHO clinical response of NAC. Therefore, total and intratumoral CD8+ T cell expressions could be suggested as a predictive marker for clinical response of NAC.KEYWORDS: breast cancer, neoadjuvant chemotherapy, CD8, clinical response, Miller Payne, intratumoral, peritumoral 
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总CD8+ T细胞和瘤内CD8+ T细胞表达与Miller Payne分级和WHO新辅助化疗临床反应相关
背景:据报道,化疗通过直接激活cd8 + T细胞簇来刺激免疫系统。新辅助化疗(NAC)被认为可以改善局部晚期乳腺癌(LABC)患者的临床反应。然而,LABC患者NAC的免疫反应相关因素评估尚未常规进行。因此,本研究基于Miller Payne分级和世界卫生组织(WHO)标准,评估nac诱导的CD8+ T细胞与化疗反应的相关性。方法:招募LABC患者,获取年龄、性别、肿瘤、淋巴结分期、组织病理分级、雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2 (HER2)和Ki67等数据。收集活检组织和乳房切除术组织,进行苏木精-伊红和CD8免疫组织化学染色。记录和测量肿瘤周围和肿瘤内CD8+ T细胞的表达。分析基于Miller Payne分级和WHO的临床反应,并将其与CD8+ T细胞表达进行相关性分析。结果:总CD8+ T细胞高表达(80%)、瘤内CD8+ T细胞高表达(82.5%)、瘤周CD8+ T细胞高表达(65%)者较多。总CD8+ T细胞表达(p=0.013)和瘤内CD8+ T细胞表达(p=0.015)与Miller Payne分级显著相关,而瘤周CD8+ T细胞表达与Miller Payne分级无显著相关。总CD8+ T细胞表达(p=0.009)和瘤内CD8+ T细胞表达(p=0.001)也与WHO临床反应显著相关。结论:总CD8+ T细胞及瘤内CD8+ T细胞表达与NAC的Miller Payne分级及WHO临床反应相关。因此,总CD8+ T细胞和肿瘤内CD8+ T细胞的表达可以作为NAC临床疗效的预测指标。关键词:乳腺癌,新辅助化疗,CD8,临床反应,Miller Payne,瘤内,瘤周
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