Quiroz-Bolaños Angel, Quintero-Ramos Antonio, Godínez-Rubí Juliana Marisol, Franco-Topete Ramon, González Porfirio Gutiérrez, Gutiérrez-Zepeda Bricia M, Becerra-Loaiza Denisse S, Topete Antonio, de Loera-Rodriguez Cesar, Toro-Arreola Alicia Del, Daneri-Navarro Adrián
Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 950 Sierra Mojada St., Independencia, Guadalajara 44340, Jalisco, Mexico.
Departamento de Microbiología y Patología, Laboratorio de Patología Diagnóstica e Inmunohistoquímica (LAPADI), Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 950 Sierra Mojada St., Independencia, Guadalajara 44340, Jalisco, Mexico.
Int J Mol Sci. 2025 Jun 18;26(12):5851. doi: 10.3390/ijms26125851.
Immunotherapy with antibodies targeting immune checkpoints, in combination with standard therapies, is one of the areas with the most significant clinical research, particularly in aggressive tumors such as triple-negative breast cancer, where there have been relevant advances with antibodies against PD-1/PD-L1. However, it is essential to define the biological and molecular factors that influence survival and response to immunotherapy, as other immune control points, such as CTLA-4, TIM-3, LAG-3, TIGIT, and VISTA, also play a role. The immune checkpoints were studied by microarrays and immunohistochemistry in 243 samples from patients with breast cancer, according to the molecular subtype. Significant differences in PD-1, PL-1, CTLA-4, and TIGIT expression were observed between triple-negative and Her-2 tumors compared to Luminal A and Luminal B tumors. No differences in VISTA expression were observed between the different molecular subtypes. Patients with high-grade tumors showed higher PD-1, PD-L1, LAG-3, and VISTA expression than low and intermediate-grade tumors. We observed a significant difference in PD-L1/TIGIT co-expression in tumor-infiltrating cells from patients with triple-negative tumors compared to patients with Luminal A, Luminal B, and Her2+ tumors. These results are relevant in the context of clinical application.
使用靶向免疫检查点的抗体进行免疫治疗,并与标准疗法相结合,是临床研究最为显著的领域之一,尤其是在三阴性乳腺癌等侵袭性肿瘤中,针对PD-1/PD-L1的抗体已取得了相关进展。然而,确定影响免疫治疗生存和反应的生物学和分子因素至关重要,因为其他免疫控制点,如CTLA-4、TIM-3、LAG-3、TIGIT和VISTA也发挥着作用。根据分子亚型,通过微阵列和免疫组织化学对243例乳腺癌患者样本中的免疫检查点进行了研究。与Luminal A和Luminal B肿瘤相比,三阴性和Her-2肿瘤在PD-1、PL-1、CTLA-4和TIGIT表达上存在显著差异。不同分子亚型之间未观察到VISTA表达的差异。高级别肿瘤患者的PD-1、PD-L1、LAG-3和VISTA表达高于低级别和中级别的肿瘤。与Luminal A、Luminal B和Her2+肿瘤患者相比,我们观察到三阴性肿瘤患者肿瘤浸润细胞中PD-L1/TIGIT共表达存在显著差异。这些结果在临床应用背景下具有相关性。