DataSheet_1_Distribution Characteristics and Prognostic Value of Immune Infiltration in Oligometastatic Breast Cancer.docx

BackgroundTo assess the distribution characteristics and the prognostic value of immune infiltration in female oligometastatic breast cancer patients.
MethodsWe retrospectively analyzed the clinicopathological data of oligometastatic breast cancer (OMBC) patients diagnosed between June 2000 and January 2020. Immune markers were quantified by immunohistochemistry on FFPE tissues in paired normal breast tissues, primary breast cancers and oligometastatic lesions. Survival analyses were performed using the Kaplan-Meier curves and Cox-proportional hazards model.
ResultsA total of 95 female OMBC patients visited Sun Yat-sen University Cancer Center between June 2000 and January 2020, and 33 of them had matched normal breast tissues, primary cancers and oligometastatic lesions and were reviewed in immune infiltration analysis. CD8 of primary tumors had a higher expression than that in matched normal tissues. The expressions of CD8 and FOXP3 were higher in the primary sites than that in the oligometastatic lesions. CD3, CD4 and CD8 were significantly lower in the intratumoral regions than that in the peritumoral regions both in primary and oligometastatic lesions. Notably, the high percentage of CD3 in the intratumoral oligometastatic lesions predicted the longer PFS and OS, and higher CD4 in the same lesions also predicted a better OS. There was obviously positive correlation between CD4/CD3 and Ki-67 in primary cancers and negative correlation between CD4/CD3 and ER in oligometastatic sites.
ConclusionWe explored immune distribution and evolution in time and space in OMBC to provide new understandings for biological behaviors of this disease and further divided patients in different prognosis.

背景 旨在探讨女性寡转移性乳腺癌（oligometastatic breast cancer, OMBC）患者免疫浸润的分布特征及其预后价值。
方法 本研究回顾性分析2000年6月至2020年1月期间确诊的寡转移性乳腺癌（OMBC）患者的临床病理资料。采用免疫组化法对配对的正常乳腺组织、原发性乳腺癌及寡转移病灶的福尔马林固定石蜡包埋（Formalin-Fixed Paraffin-Embedded, FFPE）组织中的免疫标志物进行定量检测。采用Kaplan-Meier曲线及Cox比例风险模型进行生存分析。
结果 2000年6月至2020年1月期间，中山大学肿瘤防治中心共收治95例女性OMBC患者，其中33例具备配对的正常乳腺组织、原发性癌灶及寡转移病灶，纳入免疫浸润分析。原发性肿瘤的CD8表达水平高于配对正常组织。CD8与FOXP3在原发灶的表达水平高于寡转移病灶。无论在原发灶还是寡转移病灶中，瘤内区域的CD3、CD4及CD8表达水平均显著低于瘤周区域。值得注意的是，寡转移病灶瘤内区域高比例的CD3表达可预测更长的无进展生存期（Progression-Free Survival, PFS）与总生存期（Overall Survival, OS），该病灶中高表达的CD4同样可预测更佳的OS。原发性癌组织中CD4/CD3比值与Ki-67呈显著正相关，而寡转移病灶中CD4/CD3比值与雌激素受体（Estrogen Receptor, ER）呈显著负相关。
结论 本研究阐明了OMBC患者免疫分布的时空特征与演化规律，为该疾病的生物学行为提供了全新认知，并可为患者的预后分层提供参考依据。