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)
Article
Engineering, Biomedical
Hui Jian, Xingbo Wang, PanPan Song, Xiaqing Wu, Runxiao Zheng, Yanjing Wang, Haiyuan Zhang
Summary: Spatiotemporal targeting of tumor-associated macrophages (TAMs) and tumor cells is an emerging strategy for tumor therapy. In this study, researchers developed a nanosystem that utilizes tumor microcalcifications to deliver drugs for breast cancer therapy. The nanosystem showed effective photodynamic and immunoregulatory performance in both in vitro and in vivo experiments.
ACTA BIOMATERIALIA
(2022)
Review
Oncology
Amy J. Petty, Dwight H. Owen, Yiping Yang, Xiaopei Huang
Summary: Tumor-associated macrophages (TAMs) are the most abundant leukocyte population in most solid tumors and play a significant role in promoting tumor growth and metastasis. They are influenced by the tumor microenvironment and interact with other cell populations within the tumor milieu, leading to poor outcomes in multiple tumors. Therapeutic strategies targeting TAMs in cancer treatments focus on reducing monocyte recruitment, depleting or reprogramming TAMs, and targeting inhibitory molecules to enhance TAM-mediated phagocytosis.
Review
Biochemistry & Molecular Biology
Mengjun Li, Linye He, Jing Zhu, Peng Zhang, Shufang Liang
Summary: Tumor-associated macrophages (TAMs) play a crucial role in the tumor microenvironment due to their immunosuppressive and other functions, making them important targets for anti-cancer strategies. However, the heterogeneity of TAMs makes the targeting strategy variable and uncertain. Identifying the subset specificity of TAMs may be a future option for treatment.
CELL AND BIOSCIENCE
(2022)
Review
Oncology
Xinyuan Shen, Shengcheng Zhou, Yidong Yang, Tu Hong, Ze Xiang, Jing Zhao, Chaojie Zhu, Linghui Zeng, Lingxiao Zhang
Summary: Tumor-associated macrophages (TAMs) play a crucial role in the occurrence, development, and metastasis of malignant tumors. TAMs can be divided into inflammatory/anti-tumorigenic (M1) and regenerative/pro-tumorigenic (M2) phenotypes, with the presence of M2-TAMs being closely related to the inactivation of anti-tumor immune cells. Recent advancements in utilizing nanomedicine have shown great potential in reeducating TAMs and enhancing cancer immunotherapy.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Yanjuan Sang, Qingqing Deng, Fangfang Cao, Zhengwei Liu, Yawen You, Hao Liu, Jinsong Ren, Xiaogang Qu
Summary: In this study, an iron nanotrap was used to remodel TAMs for inhibiting tumor growth by releasing oxidative stress to reprogram TAMs, ultimately inducing immune responses and suppressing tumor growth.
Article
Medicine, Research & Experimental
Yizhao Chen, Xiangling Zhu, Hanze Liu, Cunzhi Wang, Yu Chen, Huihui Wang, Yilong Fang, Xuming Wu, Yuting Xu, Chunhua Li, Xinyue Lv, Jinghua Huang, Xintong Han, Ruilin Li, Wenming Hong, Zhiying Yu, Wei Wei, Jiajie Tu
Summary: This study constructed CAR-Ms targeting HER2 and CD47, demonstrating their ability to phagocytose ovarian cancer cells and activate CD8+ cytotoxic T lymphocytes. In vivo models showed that CAR-Ms enhanced CD8+ T cell activation and led to tumor regression by affecting the tumor microenvironment.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Liya Ding, Qiwei Wang, Antons Martincuks, Michael J. Kearns, Tao Jiang, Ziying Lin, Xin Cheng, Changli Qian, Shaozhen Xie, Hye-Jung Kim, Inga-Maria Launonen, Anniina Faerkkilae, Thomas M. Roberts, Gordon J. Freeman, Joyce F. Liu, Panagiotis A. Konstantinopoulos, Ursula Matulonis, Hua Yu, Jean J. Zhao
Summary: This study reveals an adaptive immunosuppression mechanism that leads to resistance to PARP inhibition in BRCA1-mutant ovarian tumors. This resistance is mediated by an increased population of protumor tumor-associated macrophages (TAMs) and activation of the STAT3 signaling pathway. The use of STING agonists can reshape the immunosuppressive tumor microenvironment and overcome PARPi resistance in ovarian cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Nanoscience & Nanotechnology
Xiaqing Wu, Xiaoqing Han, Jiao Yan, Runxiao Zheng, Yanjing Wang, Panpan Song, Haiyuan Zhang
Summary: This study reveals the underlying mechanism of pFeOOH NRs in TAM reprogramming and exhibits the potent immunotherapeutic effect of DpFeOOH NRs.
ACS APPLIED NANO MATERIALS
(2021)
Article
Chemistry, Multidisciplinary
Jing-Yang Zhang, Fang -Man Chen, Rong Liu, Jia-Qi Luo, Yong-Cong Huang, Na Shu, Sui-Juan Zheng, Dan Shao, Kam W. Leong, Jin-Zhi Du
Summary: This study identified that the use of the toll-like receptor 7/8 agonist resiquimod (R848) can promote macrophage phagocytosis and reprogram them into an anti-tumoral phenotype. The combination with the anti-SIRP alpha antibody (aSIRP alpha) further enhances the pro-phagocytic effect. A nanoparticle-based delivery system was developed to deliver R848 and aSIRP alpha simultaneously, leading to improved macrophage-mediated cancer immunotherapy.
Article
Biophysics
Yingying Zhang, Siwen Liu, Danyan Li, Chunyan He, Dongxu Wang, Min Wei, Shaohui Zheng, Jingjing Li
Summary: This study proposes the use of nano-sized ferroferric oxide/single wall carbon nanotubes composites (Fe3O4-SWCNT) to engineer macrophages for cancer therapy. The engineered macrophages can effectively promote the polarization of endogenous M2-like macrophages to M1-like macrophages, activate tumor immune response, and inhibit tumor progression.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2023)
Article
Immunology
Franziska Brauneck, Leticia Oliveira-Ferrer, Jana Muschhammer, Tabea Sturmheit, Christin Ackermann, Friedrich Haag, Julian Schulze zur Wiesch, Yi Ding, Minyue Qi, Louisa Hell, Barbara Schmalfeldt, Carsten Bokemeyer, Walter Fiedler, Jasmin Wellbrock
Summary: This study characterizes macrophages in high-grade serous ovarian cancer (HGSOC) and reveals that these macrophages express higher levels of M2-associated receptors and co-regulatory receptors compared to healthy individuals. CD163 mRNA levels are associated with residual tumor mass and overall survival, and TIGIT expression is associated with higher tumor grading. The combination blockade of TIGIT and CD47 can enhance phagocytosis of ovarian cancer cells by macrophages.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cell Biology
Ni Tong, Zhenqiang He, Yujie Ma, Zheng Wang, Ziming Huang, Haihong Cao, Lanyang Xu, Yuheng Zou, Wanyu Wang, Chenpeng Yi, Zhixin Yin, Qirui Wang
Summary: TAMs play a crucial role in the progression of glioma, and treatment strategies targeting TAMs include inhibiting recruitment, reducing viability, and altering phenotype. Research progress has shown the potential effectiveness of anti-tumor therapy targeting TAMs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Engineering, Biomedical
Guoxin Jing, Linnan Yang, Hong Wang, Jintong Niu, Huichao Wang, Yi Gao, Youyuan Li, Bangguo Wei, Yechang Qian, Shilong Wang
Summary: This study reveals that LDHs composed of different cations have distinct abilities to regulate the polarity of TAMs. Mg-Al LDH has a stronger ability to promote the repolarization of TAMs from M2 to M1 and inhibit the formation of MDSCs compared to Mg-Fe LDH. Additionally, Mg-Al LDH inhibits tumor growth and promotes the infiltration of activated immune cells into the TME more effectively. LDHs exert their polarization ability by inhibiting the autophagy of TAMs, and this mechanism might be related to the ionic composition of LDHs.
ADVANCED HEALTHCARE MATERIALS
(2023)
Review
Immunology
Gabriel Osborn, Chara Stavraka, Rebecca Adams, Ahmad Sayasneh, Sharmistha Ghosh, Ana Montes, Katie E. Lacy, Rebecca Kristeleit, James Spicer, Debra H. Josephs, James N. Arnold, Sophia N. Karagiannis
Summary: This review discusses the role of tumor-associated macrophages (TAMs) in the ovarian cancer tumor microenvironment (TME) and the emerging strategies that target the contributions of these cells in tumor progression through the rational design of monoclonal antibodies (mAbs).
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2022)
Article
Oncology
Aman Chauhan, Alexandre Prieur, Jill Kolesar, Susanne Arnold, Lea Payen, Younes Mahi, Berengere Vire, Madison Sands, B. Mark Evers, Dominique Joubert, Lowell Anthony
Summary: Current blood-based biomarkers for neuroendocrine neoplasms lack sensitivity and specificity. This study examined the potential of human circulating progastrin as a biomarker for neuroendocrine neoplasms. The results showed that levels of circulating progastrin were significantly higher in neuroendocrine neoplasms patients and demonstrated high sensitivity and specificity. Plasma circulating progastrin may be a diagnostic blood biomarker for both low- and high-grade neuroendocrine neoplasms, but further research is needed.
Article
Medicine, General & Internal
Justin W. Gorski, Charles S. Dietrich, Caeli Davis, Lindsay Erol, Hayley Dietrich, Nicholas J. Per, Emily Lenk Ferrell, Anthony B. McDowell, McKayla J. Riggs, Megan L. Hutchcraft, Lauren A. Baldwin-Branch, Rachel W. Miller, Christopher P. DeSimone, Holly H. Gallion, Frederick R. Ueland, John R. van Nagell, Edward J. Pavlik
Summary: The study examines the role of pelvic fluid observed during transvaginal ultrasonography (TVS) in identifying ovarian malignancy. The presence and duration of fluid over successive screening encounters were analyzed. The findings suggest that pelvic free fluid identified in TVS exams is more associated with ovarian malignancy in an asymptomatic screening population.
Article
Medicine, General & Internal
Edward J. Pavlik, Emily Brekke, Justin Gorski, Lauren Baldwin-Branch, Rachel Miller, Christopher P. DeSimone, Charles S. Dietrich, Holly S. Gallion, Frederick Rand Ueland, John R. van Nagell
Summary: The study aimed to determine the effects of age, menopausal status, weight, and BMI on transvaginal ultrasound (TVS) visualization of the ovaries. The results showed that age had the greatest influence on ovarian visualization, while menopausal status, weight, and BMI also had some impact. The study concluded that TVS can effectively visualize the ovaries in older and obese women as well.
Review
Medicine, General & Internal
Laura M. Harbin, Holly H. Gallion, Derek B. Allison, Jill M. Kolesar
Summary: Ovarian cancer is a deadly gynecologic malignancy, and precision medicine and molecular biomarker testing can help improve treatment outcomes.
Article
Health Care Sciences & Services
Megan Leigh Hutchcraft, Shulin Zhang, Nan Lin, Ginny Lee Gottschalk, James W. Keck, Elizabeth A. Belcher, Catherine Sears, Chi Wang, Kun Liu, Lauren E. Dietz, Justine C. Pickarski, Sainan Wei, Roberto Cardarelli, Robert S. DiPaola, Jill M. Kolesar
Summary: This study aimed to assess the clinical utility of germline medical exome sequencing in patients recruited from a family medicine clinic and compare the mutation frequency of hereditary predisposition genes to established general population frequencies. Results showed that hereditary disease predisposition gene mutations were identified in 6.3% of the patients and 69.2% of those underwent subsequent clinical interventions. Additionally, pharmacogenomic variants were identified in 76.1% of the patients, with 4.9% being prescribed medication with pharmacogenomic implications.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Chemistry, Medicinal
Suhas S. Bhosale, Abhisek Mandal, Caixia Hou, J. Robert McCorkle, David Schweer, Kristen S. Hill, Vivekanandan Subramanian, Jill M. Kolesar, Oleg V. Tsodikov, Jurgen Rohr
Summary: A new conjugate called mithplatin, which combines the anticancer drug mithramycin with a reactive Pt(II) bearing moiety, has been developed to combat Pt-resistant ovarian cancers. This conjugate showed higher potency than cisplatin and was effective against both Pt-sensitive and Pt-resistant ovarian cancer cells.
Review
Biochemistry & Molecular Biology
Namrata Anand, Keng Hee Peh, Jill M. Kolesar
Summary: Macrophages are versatile immune cells that can adapt to external stimuli and their environment. They can be polarized into M1 subtype that has pro-inflammatory effects or M2 subtype that supports tumor growth. Repolarizing M2 to M1 has emerged as an innovative anti-cancer approach. In this review, we focus on the application of M2-M1 repolarization strategies in treating osteosarcoma, a complex bone cancer with limited response to immunotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Hannah G. McDonald, Megan M. Harper, Kristen Hill, Anqi Gao, Angelica L. Solomon, Charles J. Bailey, Miranda Lin, Mautin Barry-Hundeyin, Michael J. Cavnar, Samuel H. Mardini, Prakash J. Pandalai, Reema A. Patel, Jill M. Kolesar, Justin A. Rueckert, Lawrence Hookey, Mark Ropeleski, Shaila J. Merchant, Joseph Kim, Mei Gao
Summary: Gastric adenocarcinoma is a major cause of cancer-related deaths worldwide. We developed a novel methodology using patient-derived organoids (PDOs) to predict chemotherapy efficacy for these patients, which can help avoid unnecessary toxicities.
Article
Oncology
Zin W. W. Myint, William H. H. St Clair, Stephen E. E. Strup, Donglin Yan, Ning Li, Derek B. B. Allison, Laurie E. E. McLouth, Carleton S. S. Ellis, Peng Wang, Andrew C. C. James, Patrick J. J. Hensley, Danielle E. E. Otto, Susanne M. M. Arnold, Robert S. S. DiPaola, Jill M. M. Kolesar
Summary: CBD has anti-tumor activity against prostate cancer, and Epidiolex at a dose of 800 mg daily appears to be safe and tolerable in patients with biochemically recurrent prostate cancer.
Article
Oncology
Taylor A. Rives, Heather Pavlik, Ning Li, Lien Qasrawi, Donglin Yan, Justine Pickarski, Charles S. Dietrich, Rachel W. Miller, Frederick R. Ueland, Jill M. Kolesar
Summary: The National Comprehensive Cancer Network recommends somatic tumor testing for all epithelial ovarian cancer patients. Implementing a nurse navigator improves the rate and timeliness of molecular testing in these patients. Next Generation Sequencing reveals a higher rate of actionable mutations compared to targeted panel testing alone.
Article
Biochemistry & Molecular Biology
Spencer R. Rosario, Bowen Dong, Yali Zhang, Hua-Hsin Hsiao, Emily Isenhart, Jianmin Wang, Erin M. Siegel, Arta M. Monjazeb, Dwight H. Owen, Prasenjit Dey, Fred K. Tabung, Daniel J. Spakowicz, William J. Murphy, Stephen Edge, Sai Yendamuri, Sami Ibrahimi, Jill M. Kolesar, Patsy H. McDonald, Deepak Vadehra, Michelle Churchman, Song Liu, Pawel Kalinski, Sarbajit Mukherjee
Summary: Obesity is associated with an increased risk of various cancers, particularly gastrointestinal ones. This study aimed to investigate the metabolic differences related to obesity and sex in adenocarcinomas of the gastrointestinal tract. By analyzing serum metabolomics, RNA-sequencing, and transcriptional analysis data, the study revealed that obesity and sex influence metabolism in patients with adenocarcinomas. The findings suggest the need for further investigation into obesity and sex-related alterations in cancers to identify biomarkers for response to immunotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Laura M. Harbin, Nan Lin, Frederick R. Ueland, Jill M. Kolesar
Summary: This study evaluates the frequency and downstream effects of SYNE1 mutation in ovarian cancer, and found that SYNE1 mutation is associated with increased tumor mutation burden (TMB) and immune cell infiltration, potentially serving as an additional biomarker for immunotherapy response in ovarian cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Nathan D. Seligson, Jill M. Kolesar, Benish Alam, Laura Baker, Jatinder K. Lamba, Brooke L. Fridley, Ameen A. Salahudeen, Daniel L. Hertz, J. Kevin Hicks
Summary: Precision medicine has greatly improved the clinical care for cancer patients by developing targeted therapies, identifying inherited cancer predisposition syndromes, and optimizing pharmacotherapy through pharmacogenetics. It is argued that integrating pharmacogenomics into paired germline/somatic genomic testing would be an efficient method for increasing access to pharmacogenomic testing.