Changes and prognostic values of tumor-infiltrating lymphocyte subsets after primary systemic therapy in breast cancer
Changes and prognostic values of tumor-infiltrating lymphocyte subsets after primary systemic therapy in breast cancer
复制标题
DOI：
10.1371/journal.pone.0233037
复制
发表时间：
2020-05-13
期刊：
影响因子：
3.7
通讯作者：
Park, So Yeon
中科院分区：
文献类型：
--
作者：
Ahn, Soomin;Chung, Yul Ri;Park, So Yeon
肿瘤浸润淋巴细胞（TIL）水平在未经治疗的乳腺癌中具有预后和预测价值。然而，关于治疗后乳腺癌中TIL亚群的变化及其临床意义一直存在争议。本研究旨在探讨乳腺癌原发性系统治疗（PST）后TIL亚群浸润的变化及其预后意义。纳入了155例蒽环类或蒽环类加紫杉烷类PST后有残留疾病的患者。分析乳腺癌患者PST前后肿瘤内和间质中TIL亚群（CD8+、CD4+和FOXP3+）的数量及其变化，并沿着其与患者临床病理特征和预后的关系。总体而言，PST后肿瘤内CD8+和CD4+ TIL增加，而间质TIL减少。PST后肿瘤内和间质FOXP3+ TIL均减少。化疗敏感组[残留癌负荷（RCB）I类和II类]显示与整个组相同的肿瘤内CD8+ TIL变化模式，而化疗耐药组（RCB III类）显示PST后肿瘤内CD8+ TIL浸润无显著变化。对每个TIL亚群的生存分析及其比值显示，PST后高水平的肿瘤内、间质和总CD8+ TIL浸润是患者生存期延长的独立预测因素。在亚组分析中，PST后的CD8+ TIL浸润在化疗耐药组中显示了预后意义，但在化疗敏感组中没有。总之，PST后，CD8+、CD4+和FOXP3+ TIL在瘤内和间质中的浸润发生变化。尤其是肿瘤内CD8+ TIL的增加与化疗反应性相关。此外，PST后残留肿瘤中的CD8+ TIL状态可用作接受PST的乳腺癌患者的潜在预后标志物，并为化疗耐药组提供额外的预后信息。
Tumor-infiltrating lymphocyte (TIL) levels have prognostic and predictive values in treatment-naive breast cancers. However, there have been controversies regarding TIL subset changes and their clinical implications in post-treatment breast cancers. This study aimed to explore change and prognostic significance of TIL subset infiltration after primary systemic therapy (PST) in breast cancer. One-hundred-fifty-five patients who had residual disease after anthracycline- or anthracycline plus taxane-based PST were included. The quantities of intratumoral and stromal TIL subsets (CD8+, CD4+, and FOXP3+ TILs) in pre- and post-PST breast cancer samples, as well as changes between them, were analyzed along with their correlations with clinicopathologic features and outcome of patients. As a whole, intratumoral CD8+ and CD4+ TILs increased after PST while stromal TILs decreased. Both intratumoral and stromal FOXP3+ TILs decreased after PST. The chemo-sensitive group [residual cancer burden (RCB) class I and II] showed the same pattern of change in intratumoral CD8+ TILs as the whole group, whereas the chemo-resistant group (RCB class III) showed no significant change in intratumoral CD8+ TIL infiltration after PST. Survival analyses for each TIL subset as well as their ratios revealed that high levels of intratumoral, stromal, and total CD8+ TIL infiltration after PST were independent predictors of longer patient survival. In subgroup analyses, CD8+ TIL infiltration after PST revealed prognostic significance in the chemo-resistant group but not in the chemo-sensitive group. In conclusion, infiltration of CD8+, CD4+, and FOXP3+ TIL changed after PST in the intratumoral and stromal compartments. Especially, increase of intratumoral CD8+ TILs was associated with chemo-responsiveness. Moreover, CD8+ TIL status in residual tumors after PST may be used as a potential prognostic marker in breast cancer patients who receive PST and provide additional prognostic information to chemo-resistant group.