Article
Biochemistry & Molecular Biology
Duaa Alkaabi, Kholoud Arafat, Shahrazad Sulaiman, Aya Mudhafar Al-Azawi, Samir Attoub
Summary: Triple-negative breast cancer (TNBC) is a highly aggressive type of breast cancer with poor prognosis. This study investigated the role of programmed death-ligand 1 (PD-L1) in TNBC MDA-MB-231 cells independent of its binding to PD-1 receptors on T cells. The study found that knockout of PD-L1 inhibited cell proliferation, colony formation, migration, and invasion in vitro, as well as tumor growth in a chick embryo model in vivo. PD-L1 knockout also affected the expression of several downstream proteins involved in tumor progression. These findings suggest that targeting PD-L1 could be a potential therapeutic strategy for TNBC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Huijie Yang, Min Xue, Peng Su, Yan Zhou, Xin Li, Zhongbo Li, Yan Xia, Chenmiao Zhang, Mingxi Fu, Xiuxia Zheng, Guosheng Luo, Tian Wei, Xinxing Wang, Yinlu Ding, Jian Zhu, Ting Zhuang
Summary: In this study, the tumor-suppressive function of RNF31 in triple negative breast cancer (TNBC) was demonstrated. It was found that RNF31 could regulate the Hippo signaling pathway and its depletion increased TNBC cell proliferation and migration. Clinical data also showed that RNF31 expression was correlated with longer relapse-free survival in TNBC patients.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Sung Gwe Ahn, Seon-Kyu Kim, Jonathan H. Shepherd, Yoon Jin Cha, Soong June Bae, Chungyeul Kim, Joon Jeong, Charles M. Perou
Summary: The SP142 PD-L1 assay is a companion diagnostic for atezolizumab in metastatic triple-negative breast cancer (TNBC). Through studying 149 TNBC samples, it was found that PD-L1-positive TNBC samples had higher levels of CD8+ T cells, stromal tumor-infiltrating lymphocytes, and immunomodulatory TNBCtype compared to PD-L1-negative samples. The SP142-guided gene expression signature consisting of 94 immune-related genes was associated with improved response and survival in multiple TNBC cohorts.
BREAST CANCER RESEARCH AND TREATMENT
(2021)
Article
Pharmacology & Pharmacy
Simona Camorani, Silvia Tortorella, Lisa Agnello, Chiara Spanu, Annachiara D'Argenio, Roberto Nilo, Antonella Zannetti, Erica Locatelli, Monica Fedele, Mauro Comes Franchini, Laura Cerchia
Summary: This study presents a novel aptamer-based platform for the targeted delivery of siRNA to triple-negative breast cancer cells. By utilizing cell-targeting and internalizing aptamers, this delivery system specifically delivers siRNA to TNBC cells, resulting in efficient suppression of PD-L1 expression.
Article
Biotechnology & Applied Microbiology
Hsuan-Chen Liu, Simone Capuani, Andrew A. Badachhape, Nicola Di Trani, Daniel Davila Gonzalez, Robin S. Vander Pol, Dixita I. Viswanath, Shani Saunders, Nathanael Hernandez, Ketan B. Ghaghada, Shu-Hsia Chen, Elizabeth Nance, Ananth V. Annapragada, Corrine Ying Xuan Chua, Alessandro Grattoni
Summary: This study demonstrates the efficacy of using the nanofluidic drug-eluting seed (NDES) platform for sustained intratumoral delivery of immune checkpoint inhibitors (ICI). The NDES-treated cohort showed sustained levels of the therapeutic in the tumor, with minimal off-target organ distribution.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Yuting Zhou, Zhongping Liang, Yingjie Xia, Shuai Li, Jiali Liang, Zhixiang Hu, Chengbin Tang, Qing Zhao, Qing Gong, Yongchang Ouyang
Summary: This study identifies RBMS3 as a crucial regulator of PD-L1 in triple-negative breast cancer. RBMS3 binds to CD274 mRNA, stabilizing PD-L1 levels and promoting cell migration. Combining RBMS3 inhibition with auranofin enhances anti-tumor T-cell immunity and improves the efficacy of cancer immunotherapy.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Yanlin Bian, Tong Lin, Tanja Jakos, Xiaodong Xiao, Jianwei Zhu
Summary: In this study, three novel dual-targeting fusion proteins were designed and constructed to enhance antigen-antibody affinity. Among these proteins, Pro3 showed the best performance in activating the anti-tumor immune response. Pro3 demonstrated superior T cell proliferation and macrophage engulfment compared to the prototype IAB, while retaining comparable ADCC activity. The improved design of the dual-targeting immunomodulatory protein Pro3 has potential for clinical applications.
Article
Biochemistry & Molecular Biology
Julio M. Pimentel, Jun-Ying Zhou, Gen Sheng Wu
Summary: This study identifies the important role of PD-L1 in TRAIL resistance, which is mediated by increased ERK activation. Knockdown of ERK or inhibition of its activation can decrease PD-L1 expression and increase TRAIL-induced cell death.
MOLECULAR CARCINOGENESIS
(2022)
Article
Oncology
Seung Ho Baek, Jee Hung Kim, Soong June Bae, Jung Hwan Ji, Yangkyu Lee, Joon Jeong, Yoon Jin Cha, Sung Gwe Ahn
Summary: The study suggests that multiple PD-L1 testing using different tumor samples is necessary in TNBC patients, as a single test may not accurately represent the PD-L1 status. This can help identify more patients who are eligible for immune checkpoint blockade treatments.
Article
Oncology
Fara Braso-Maristany, Miriam Sanso, Nuria Chic, Debora Martinez, Blanca Gonzalez-Farre, Esther Sanfeliu, Lucio Ghiglione, Esther Carcelero, Javier Garcia-Corbacho, Marcelo Sanchez, Dolors Soy, Pedro Jares, Vicente Peg, Cristina Saura, Montserrat Munoz, Aleix Prat, Ana Vivancos
Summary: A case study demonstrated significant response to atezolizumab in a PD-L1-negative TNBC patient, potentially due to factors such as high TMB, presence of APOBEC genetic signatures, tumor inflammation signature, and HER2-enriched subtype. Additional translational studies are needed to identify biomarkers for response to immune checkpoint inhibitors beyond PD-L1 expression in TNBC patients.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Hyungjoo Kim, Je-Min Choi, Kyung-min Lee
Summary: Immune checkpoint blockades have greatly improved cancer treatment, but a significant number of TNBC patients do not respond to these therapies, and mechanisms of resistance are poorly understood. This review focuses on biomarkers and recent advances in understanding molecular mechanisms of resistance to ICBs in TNBC.
Article
Biochemistry & Molecular Biology
Liubov A. Tashireva, Anna Yu. Kalinchuk, Tatiana S. Gerashchenko, Maksim Menyailo, Anna Khozyainova, Evgeniy V. Denisov, Vladimir M. Perelmuter
Summary: The problem of identifying the appropriate patients who would benefit the most from immunotherapy is critical. In this study, 18 triple-negative breast cancer patients were enrolled. Several tests were conducted to analyze the tumor characteristics. The results showed that there are differences in the tumor microenvironment and immune reactions, which may explain the lack of response to immune checkpoint inhibitors in triple-negative breast cancer patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Minglu Zhou, Chaohui Luo, Zhou Zhou, Lian Li, Yuan Huang
Summary: The study demonstrated that a combinatory approach of inducing immunogenic cell death (ICD) and inhibiting CXCR4 in TNBC could improve the effectiveness of anti-PD-L1 therapy by enhancing T cell response, reducing immunosuppressive cells, removing physiological barriers in tumors, and inhibiting the formation of pre-metastatic niche. As a result, non-responsive TNBC showed robust responsiveness to anti-PD-L1 therapy with complete eradication of orthotopic tumors, inhibition of pulmonary metastasis, and durable memory effects against tumor recurrence.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Biochemistry & Molecular Biology
Yufan Qiu, Yi Yang, Riyao Yang, Chunxiao Liu, Jung-Mao Hsu, Zhou Jiang, Linlin Sun, Yongkun Wei, Chia-Wei Li, Dihua Yu, Jin Zhang, Mien-Chie Hung
Summary: The study reveals that PD-1 can be secreted in an exosomal form by activated T cells and interact remotely with PD-L1. This interaction can attenuate the suppression of tumor-specific cytotoxic T cell activity by PD-L1, restoring tumor surveillance.
Article
Medicine, Research & Experimental
Hongpei Tan, Jiahao Liu, Jing Huang, Yanan Li, Qiongxuan Xie, Yuqian Dong, Ze Mi, Xiaoqian Ma, Pengfei Rong
Summary: Our study demonstrates that combining DMKG with radioimmunotherapy is an effective strategy for treating triple-negative breast cancer by promoting apoptosis, immunogenic death, and remodeling the tumor immune microenvironment.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)