Li Peng, Yuan Wenhui, Wu Ruan, Zeng Chuqian, Li Ke, Lu Ligong
Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China.
The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou, China.
Front Oncol. 2022 Jun 29;12:917400. doi: 10.3389/fonc.2022.917400. eCollection 2022.
Endocrine therapy is considered as an effective strategy for estrogen and progestogen receptor (ER and PR)-positive breast cancer (BRCA) patients, whereas resistance to these agents is the major cause of BRCA mortality in women. Immune checkpoint receptor (ICR) blockade is another approach to treat BRCA, but the response rate of this approach for non-triple-negative breast cancer (non-TNBC) is relatively low. Recently, the androgen receptor (AR) has been identified as a tumor suppressor in ER-positive BRCA; however, the relationship between the levels of androgens and ICRs on T cells in BRCA is unclear. We observed that testosterone and dihydrotestosterone (DHT) in patients with HER2 and Luminal B were significantly lower than those in healthy controls, and the expression of AR has significant correlation with overall survival (OS) advantage for Luminal B patients. Moreover, testosterone and DHT were positively correlated with the PD-1 expression on Vδ1 T cells in HER2 and Luminal B patients. These results suggest a potential approach of combining androgens with PD-1 blockade for treating HER2 and Luminal B breast cancer.
内分泌治疗被认为是雌激素和孕激素受体（ER和PR）阳性乳腺癌（BRCA）患者的有效治疗策略，而对这些药物的耐药性是女性BRCA死亡的主要原因。免疫检查点受体（ICR）阻断是治疗BRCA的另一种方法，但这种方法对非三阴性乳腺癌（non-TNBC）的反应率相对较低。最近，雄激素受体（AR）已被确定为ER阳性BRCA中的肿瘤抑制因子；然而，BRCA中雄激素水平与T细胞上ICR之间的关系尚不清楚。我们观察到，HER2和Luminal B型患者的睾酮和双氢睾酮（DHT）明显低于健康对照，并且AR的表达与Luminal B型患者的总生存期（OS）优势显著相关。此外，HER2和Luminal B型患者的睾酮和DHT与Vδ1 T细胞上PD-1的表达呈正相关。这些结果提示了一种将雄激素与PD-1阻断相结合治疗HER2和Luminal B型乳腺癌的潜在方法。
