Review
Oncology
Nisha Kumari, Seung Hong Choi
Summary: Cancer immunotherapy has had limited success, but nanoparticles have emerged as crucial tools in targeting tumor-associated macrophages (TAMs) and improving therapy outcomes. Current strategies include restricting TAMs survival, inhibiting TAMs recruitment, and repolarizing tumor-supportive TAMs to an antitumor phenotype.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Seung Joon Lee, Hannah Yang, Woo Ram Kim, Yu Seong Lee, Won Suk Lee, So Jung Kong, Hye Jin Lee, Jeong Hun Kim, Jaekyung Cheon, Beodeul Kang, Hong Jae Chon, Chan Kim
Summary: STING activation can normalize the peritoneal vascular and immune microenvironment, converting immunologically cold peritoneal tumors into T-cell-inflamed tumors and providing a rationale for a novel combination therapeutic strategy for peritoneal carcinomatosis in colon cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Biophysics
Chunmei Chen, Wei Zhang, Shi-Yu Lu, Jingjing Wang, Yixin Tan, Sheng Zhao, Yi Ouyang, Luen Xu, Benqing Zhou, Xuntao Yin, Haitao Ran, Hui Liu
Summary: Tumor-associated macrophages (TAMs)-mediated immunotherapy has attracted attention, but the acidic tumor microenvironment limits TAMs' phenotype. This study developed novel LDH-PAA@DOX NSs as deacidification agents to repolarize TAMs and achieve tumor elimination through combined chemodynamic therapy and immunotherapy.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2023)
Article
Chemistry, Multidisciplinary
Qiuqun Xiao, Jinyan Huang, Xing Wang, Zehong Chen, Weiqi Zhang, Fengjiao Liu, Jiejing Li, Zhimou Yang, Jie Zhan, Yanbin Cai
Summary: This study demonstrates the potential of a supramolecular peptide amphiphile drug-delivery system (SPADS) to reprogram macrophages and reshape the tumor immune microenvironment (TIM) for enhanced tumor immunotherapy outcomes. By specifically targeting M2-type macrophages, the SPADS induce repolarization into M1-type macrophages, improving macrophagic antitumor activity and immunoregulatory function. Additionally, the SPADS disrupt immune evasion mechanisms in tumor cells and synergize with anti-PD-1 antibody therapy to enhance the immune system's ability to recognize and eliminate tumor cells.
Article
Oncology
Noor Shakfa, Deyang Li, Gwenaelle Conseil, Elizabeth D. Lightbody, Juliette Wilson-Sanchez, Ali Hamade, Stephen Chenard, Natasha A. Jawa, Brian J. Laight, Afrakoma Afriyie-Asante, Kathrin Tyryshkin, Martin Koebel, Madhuri Koti
Summary: This study revealed that PTEN deficiency in high-grade serous ovarian carcinoma leads to an immunosuppressive tumor microenvironment, resulting in decreased response to chemotherapy and overall survival. Activation of the STING pathway can improve chemotherapy response and overall survival in PTEN-deficient tumors.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Chemistry, Multidisciplinary
Huanling Guo, Jinsheng Huang, Yang Tan, Wenxin Wu, Tongyi Huang, Nan Zhang, Shuling Chen, Chunyang Zhang, Xiaoyan Xie, Xintao Shuai, Ming Xu
Summary: The blockade of PD-1/PD-L1 did not extend the progression-free survival of patients with liver metastases from colorectal cancers after radiofrequency ablation (RFA) treatment. Our study in mice model showed that PD-1/PD-L1 immune checkpoint blockade therapy after RFA only temporarily inhibited tumor progression due to limited mature dendritic cells (DCs) and insufficient infiltration/activation of cytotoxic T lymphocytes (CTLs). Activation of stimulator of interferon gene (STING) impacting tumor-infiltrating DCs and CD8+ T cells was also transient after RFA. Therefore, a nanovesicle capable of controlled release of anti-PD-L1 antibody (alpha PD-L1) and STING agonist inside the tumor was developed to induce a strong anti-cancer immune response and long-term inhibition of tumor progression after RFA.
Article
Oncology
Ziqi Liu, Dan Wang, Jiarong Zhang, Pingjuan Xiang, Zhaoyang Zeng, Wei Xiong, Lei Shi
Summary: The cGAS-STING signaling pathway plays a critical role in regulating the tumor microenvironment by affecting immune activation. It has been widely recognized for its ability to combat tumor progression and induce immune responses, leading to the development of immunotherapies. However, recent findings also suggest its diverse roles in shaping the tumor microenvironment, including functions that promote tumor progression.
Review
Oncology
Afsaneh Amouzegar, Manoj Chelvanambi, Jessica N. Filderman, Walter J. Storkus, Jason J. Luke
Summary: Immunotherapies have significantly impacted cancer treatment, yet some patients do not respond effectively. Recent efforts have been focused on identifying targets that could enhance anti-tumor immune responses, with STING pathway being one novel and promising target. Research on STING agonists has opened avenues for developing more effective strategies in cancer immunotherapy.
Article
Oncology
Si-Yu Wu, Yi Xiao, Jin-Li Wei, Xiao-En Xu, Xi Jin, Xin Hu, Da-Qiang Li, Yi-Zhou Jiang, Zhi-Ming Shao
Summary: This study identified two distinct microenvironment phenotypes, 'inflamed' and 'non-inflamed', within the classic basal-like subtype of TNBC, and revealed that MYC amplification and overexpression led to the formation of the non-inflamed TIME. Combination therapy with a DNA methyltransferase inhibitor and immunotherapy reversed T cell exhaustion and improved T cell function, resulting in potent antitumor activity in MYC-overexpressing TNBC.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Medicine, Research & Experimental
Qian Zhou, Jinxia Liang, Tong Yang, Jin Liu, Bo Li, Yingchang Li, Zhenzhen Fan, Weida Wang, Wensheng Chen, Sujing Yuan, Meng Xu, Qigui Xu, Zhidong Luan, Zhongjun Xia, Penghui Zhou, Yadong Huang, Liang Chen
Summary: The study revealed that Carfilzomib effectively converted M2 macrophages into M1-like macrophages, reshaped the tumor microenvironment, and synergized with PD-1 inhibitors to treat autochthonous lung cancers.
EMBO MOLECULAR MEDICINE
(2022)
Article
Oncology
Mohammad Alshebremi, Suzanne L. Tomchuck, Jay T. Myers, Daniel T. Kingsley, Saada Eid, Muta Abiff, Melissa Bonner, Shahrazad T. Saab, Sung Hee Choi, Alex Yee-Chen Huang
Summary: The tumor cell-intrinsic STING pathway plays a crucial role in the effectiveness of cryoablation, and the expression of STING-related signaling components may serve as a potential therapy response biomarker.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Biochemistry & Molecular Biology
Shubhasmita Mohapatra, Jared Cafiero, Khosrow Kashfi, Parag Mehta, Probal Banerjee
Summary: The standard treatment for most malignant solid tumors involves tumor resection followed by chemo- and radiation therapy. However, this approach has not been effective in controlling recurrence or increasing the survival rate of primary glioblastoma (GBM) patients. Immunotherapies that use genetic modifications of Tc cells or inhibition of proteins have not been successful in treating GBM either. A series of preclinical studies have shown that re-educating GBM-associated microglia and macrophages (TAMs) can lead to the recruitment of activated, GBM-eliminating NK cells and rescue GBM mice. This review discusses the question of why we don't get cancer more often and strategies for re-educating TAMs to take on their original role as sentinels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, Research & Experimental
Degao Chen, Xiaomei Zhang, Zhongjun Li, Bo Zhu
Summary: The article discusses the metabolic regulation between TME and TAMs. Immune molecules from TAMs and TME act as mediators of signal transduction. TAMs are influenced by metabolites produced in the TME.
Article
Oncology
Hanane Chamma, Isabelle K. Vila, Clara Taffoni, Andrei Turtoi, Nadine Laguette
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a cancer with poor prognosis and limited response to immunotherapy. Novel strategies targeting the Stimulator of Interferon Genes (STING) protein have shown the potential to elicit response to immunotherapy. However, the effectiveness of STING activation varies depending on the cellular and tissue context, emphasizing the importance of understanding tumor heterogeneity in determining its benefits for PDAC patients.
Article
Chemistry, Multidisciplinary
Dan Liu, Shuang Liang, Kongshuo Ma, Qian-Fang Meng, Xingang Li, Jian Wei, Mengli Zhou, Kaiqing Yun, Yuanwei Pan, Lang Rao, Xiaoyuan Chen, Zhaohui Wang
Summary: Tumor microenvironment-responsive nanoparticles are utilized to activate the stimulator of interferon genes (STING) and Toll-like receptor 4 (TLR4) pathways, leading to increased secretion of interferons and pro-inflammatory cytokines and creating an immune-supportive microenvironment. Combined with an anti-PD-1 antibody, these nanoparticles show synergistic efficacy and induce systemic antitumor memory.
ADVANCED MATERIALS
(2023)