Review
Immunology
Meina Yan, Yifeng Gu, Hongxia Sun, Qinghong Ge
Summary: Tumor immunity is a rapidly growing field that focuses on immune cells within the tumor microenvironment. Neutrophil extracellular traps (NETs), composed of histones and granule proteins, have gained attention due to their association with tumor growth, metastasis, and drug resistance. Increased NET formation has been linked to immune exclusion and inhibition of T-cell mediated antitumor immune responses. This review summarizes the recent progress in understanding the roles of NETs in tumor and anti-tumor immunity, highlighting the challenges in the field. NETs may serve as a promising therapeutic target for tumor immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Dominique S. Rubenich, Priscila O. de Souza, Natalia Omizzollo, Mariana R. Aubin, Paulo J. Basso, Luisa M. Silva, Eloisa M. da Silva, Fernanda C. Teixeira, Gabriela F. S. Gentil, Jordana L. Domagalski, Maico T. Cunha, Kerolainy A. Gadelha, Leonardo F. Diel, Nicolly E. Gelsleichter, Aline S. Rubenich, Gabriela S. Lenz, Aline M. de Abreu, Giselle M. Kroeff, Ana H. Paz, Fernanda Visioli, Marcelo L. Lamers, Marcia R. Wink, Paulo V. Worm, Anelise B. Araujo, Jean Sevigny, Niels O. S. Camara, Nils Ludwig, Elizandra Braganhol
Summary: This study demonstrates that neutrophils are reprogrammed by the tumor to ultimately promote the progression of glioblastoma (GB). The communication between GB and neutrophils directly promotes an immunosuppressive tumor microenvironment (TME). These findings are crucial for understanding tumor progression and the role of immune cells in this process.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Miriam Ratliff, Kianush Karimian-Jazi, Dirk C. Hoffmann, Laurel Rauschenbach, Matthias Simon, Ling Hai, Henriette Mandelbaum, Marc C. Schubert, Tobias Kessler, Stefanie Uhlig, Daniel Dominguez Azorin, Erik Jung, Matthias Osswald, Gergely Solecki, Mate E. Maros, Varun Venkataramani, Martin Glas, Nima Etminan, Bjoern Scheffler, Wolfgang Wick, Frank Winkler
Summary: This study used real-time 3D in vivo 2-photon laser scanning microscopy to longitudinally observe the invasion and proliferation of tumor cells. It found that highly invasive tumor cells also have high proliferative capability during brain colonization. The phenotype of tumor cells gradually transitions into slower-cycling glioblastoma cells.
Article
Oncology
Zhengjun Zhou, Pengcheng Wang, Rongqi Sun, Jia Li, Zhiqiang Hu, Haoyang Xin, Chubin Luo, Jian Zhou, Jia Fan, Shaolai Zhou
Summary: The interaction between TANs and TAMs enhances the proliferation and invasion abilities of ICC cells, promoting ICC progression. They can produce Oncostatin M and interleukin-11 in co-culture, activating STAT3 signaling in ICC cells, and silencing STAT3 can disrupt the pro-tumor effect of TANs and TAMs on ICC.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Oncology
Jie Deng, Rongqi Jiang, Enqing Meng, Hao Wu
Summary: CXCL5, a chemokine, plays a critical role in human malignant tumors, potentially associated with tumor metastasis and angiogenesis. Regulating CXCL5 may be a promising approach for tumor therapy.
FRONTIERS IN ONCOLOGY
(2022)
Review
Immunology
Richard Felix Kraus, Michael Andreas Gruber
Summary: Neutrophils, as part of the innate immune response, play a crucial role in defending against pathogens but can also mediate tissue damage in various diseases. Recent scientific advancements have expanded our understanding of neutrophils, highlighting their importance beyond immune defense to maintaining overall body integrity. This review delves into the role of neutrophils, their migration processes, immune properties, and behavior in cancer environments.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Iori Motoo, Takayuki Ando, Takeru Hamashima, Shinya Kajiura, Miho Sakumura, Yuko Ueda, Aiko Murayama, Kohei Ogawa, Kenichiro Tsukada, Akira Ueda, Nobuhiro Suzuki, Naokatsu Nakada, Koji Nakashima, Ayumu Hosokawa, Ichiro Yasuda
Summary: This study aimed to analyze the progression pattern and mechanism of response to ICIs in patients with gastric cancer. Non-systemic progression was associated with improved overall survival, while liver metastasis was a predictive factor of systemic progression during ICIs.
FRONTIERS IN ONCOLOGY
(2023)
Article
Pharmacology & Pharmacy
Amna A. Saddiq, Ali H. El-Far, Shymaa Abdullah Mohamed Abdullah, Kavitha Godugu, Omar A. Almaghrabi, Shaker A. Mousa
Summary: The combination of curcumin, thymoquinone, and 3, 3'-diindolylmethane exhibited anticancer effects on lung and liver cancer cells, inhibiting cell proliferation and migraton, inducing apoptosis, and reducing tumor weight and angiogenesis.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Ludmila Alekseeva, Nadezhda Mironova
Summary: Many studies have shown an increase in circulating cell-free DNA levels in cancer patients, which can originate from tumor cells or immune cells and play a significant role in promoting tumor growth and invasion. Studying deoxyribonucleases as anticancer and antimetastatic agents is important and promising in preventing and prohibiting tumor progression and metastasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Patrick P. Mcdonald, Franziska Graf Leifer, Jessica Basso, Dan Lasala, Dedong Li, Kuan-Ju Chen, Jimin Zhang, Walter R. Perkins, David C. Cipolla
Summary: The efficacy of the DPP-1 inhibitor brensocatib was assessed in rat and mouse models, showing significant reduction in bone marrow NSP levels and improvement in disease score. In the mouse model, brensocatib even demonstrated similar efficacy to anti-TNF antibodies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Nanoscience & Nanotechnology
Adityanarayan Mohapatra, Santhosh Kalash Rajendrakumar, Gopalakrishnan Chandrasekaran, Vishnu Revuri, Padmanaban Sathiyamoorthy, Yong-Kyu Lee, Jae Hyuk Lee, Seok-Yong Choi, In-Kyu Park
Summary: A peroxidase-mimicking nanoscavenger was developed to block the secretion of reactive oxygen species (ROS) and proinflammatory cytokines in gouty arthritis induced by monosodium urate (MSU) crystals. The nanoparticles alleviated joint swelling by abrogating ROS and inflammatory cytokine secretions from proinflammatory macrophages, preventing neutrophil infiltration and fluid buildup at the inflammation site. The treatment also reduced macrophage and neutrophil influx in the injured region in zebrafish and mouse models. Overall, the strategy of using biomineralized nanoscavengers shows clinical significance in dual blocking of peroxides and COX2 to prevent inflammation cell influx.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Review
Oncology
Kavita Rawat, Saima Syeda, Anju Shrivastava
Summary: Neutrophils are key cells of the innate immune system, mediating host defense through a range of effector functions, but their excessive release can be detrimental and has been associated with various inflammatory diseases including cancer, providing potential therapeutic targets.
CANCER AND METASTASIS REVIEWS
(2021)
Article
Immunology
M. Fernanda Palominos, Cristian Calfun, Gino Nardocci, Danissa Candia, Jorge Torres-Paz, Kathleen E. Whitlock
Summary: In the olfactory organs, a unique population of neutrophils associated with both the olfactory epithelia and the lymphatic vasculature suggests a dual olfactory-immune function.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Endocrinology & Metabolism
Tobias Hallen, Gudmundur Johannsson, Rahil Dahlen, Camilla A. M. Glad, Charlotte Orndal, Angelica Engvall, Helena Caren, Thomas Skoglund, Daniel S. Olsson
Summary: This study explored DNA methylation patterns associated with tumor progression in patients with nonfunctioning pituitary adenomas (NFPAs). The results showed that some methylation sites were associated with tumor progression and could potentially serve as biomarkers for early identification of tumor progression.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Review
Oncology
Leena Arora, Durba Pal
Summary: The molecular understanding of carcinogenesis and tumor progression relies on the intra and inter-tumoral heterogeneity. Recent advances in single-cell sequencing technology have provided insights into the complexity of the tumor microenvironment, guiding potential therapeutic strategies.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Fabio Quaglia, Shiv Ram Krishn, Yanqing Wang, David W. Goodrich, Peter McCue, Andrew Kossenkov, Amy C. Mandigo, Karen E. Knudsen, Paul H. Weinreb, Eva Corey, William K. Kelly, Lucia R. Languino
Summary: The study demonstrates an upregulation of the α V β3 integrin in NEPrCa primary and metastatic lesions, while the α V β6 integrin is confined to prostate adenocarcinoma. The findings suggest that α V β3 integrin may promote a shift in lineage plasticity towards a NE phenotype and serve as a biomarker for early detection of NE differentiation in prostate cancer.
Article
Multidisciplinary Sciences
Kevin Alicea-Torres, Emilio Sanseviero, Jun Gui, Jinyun Chen, Filippo Veglia, Qiujin Yu, Laxminarasimha Donthireddy, Andrew Kossenkov, Cindy Lin, Shuyu Fu, Charles Mulligan, Brian Nam, Gregory Masters, Fred Denstman, Joseph Bennett, Neil Hockstein, Agnieszka Rynda-Apple, Yulia Nefedova, Serge Y. Fuchs, Dmitry Gabrilovich
Summary: Type I interferon receptor signaling serves as a universal mechanism restricting MDSC suppressive activity, with downregulation of IFNAR1 required for activation of immune suppressive properties in MDSC. Modulating IFNAR1 undermines MDSC suppressive activity and has potent anti-tumor effects.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Ekta Agarwal, Aaron R. Goldman, Hsin-Yao Tang, Andrew V. Kossenkov, Jagadish C. Ghosh, Lucia R. Languino, Valentina Vaira, David W. Speicher, Dario C. Altieri
Summary: Parkin, an E3 ubiquitin ligase altered in Parkinson's disease, is shown to suppress tumor growth by shutting off mitochondrial dynamics and inhibiting the non-oxidative phase of the pentose phosphate pathway. This tumor suppression function of Parkin requires its E3 ligase activity and can be reversed by antioxidants, independently of mitophagy. Cancer metabolic networks are identified as potential oncogenes directly targeted by endogenous tumor suppression mechanisms.
Article
Oncology
Shiv Ram Krishn, Vaughn Garcia, Nicole M. Naranjo, Fabio Quaglia, Christopher D. Shields, Maisha A. Harris, Andrew Kossenkov, Qin Liu, Eva Corey, Dario C. Altieri, Lucia R. Languino
Summary: The alpha V beta 6 integrin is upregulated during prostate cancer progression and specifically expressed in androgen receptor-negative tumors. By delivering ITGB6-targeting siRNAs into PrCa cells using sEVs, the expression of beta 6 subunit can be downregulated, leading to reduced cell adhesion and migration in PrCa cells.
CANCER BIOLOGY & THERAPY
(2022)
Article
Oncology
Scott D. Siegel, Madeline M. Brooks, Jennifer Sims-Mourtada, Zachary T. Schug, Dawn J. Leonard, Nicholas Petrelli, Frank C. Curriero
Summary: This study used geocoding and electronic health records to identify hot spots of triple-negative breast cancer (TNBC) and found a correlation between these hot spots and higher rates of unhealthy alcohol use and obesity. This provides guidance for cancer control and prevention efforts in community cancer centers.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Biochemistry & Molecular Biology
Michael P. Young, Zachary T. Schug, David M. Booth, David Yule, Katsuhiko Mikoshiba, Gyorgy Hajnoczky, Suresh K. Joseph
Summary: The interplay between calcium signaling and cellular metabolism is not well understood. In this study, the authors investigated the metabolic and bioenergetic responses of human cancer cells with loss of cytosolic and/or mitochondrial calcium signaling. The results showed that constitutive calcium signaling is dispensable for the bioenergetic needs of the cells, but increased energy expenditure in mitochondria-deficient cells may lead to bioenergetic failure under metabolic stress.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Biotechnology & Applied Microbiology
Zachary E. Stine, Zachary T. Schug, Joseph M. Salvino, Chi Dang
Summary: In the past century, there have been significant advancements in targeting cancer metabolism, but progress in the past decade has been limited. Some metabolism-based drugs for cancer have been successfully developed and are in clinical trials. However, consideration of the metabolism of non-cancer cells is crucial for successful treatment of cancer.
NATURE REVIEWS DRUG DISCOVERY
(2022)
Article
Biochemistry & Molecular Biology
Anna Han, Vivian Chua, Usman Baqai, Timothy J. Purwin, Nelisa Bechtel, Emily Hunter, Manoela Tiago, Erin Seifert, David W. Speicher, Zachary T. Schug, J. William Harbour, Andrew E. Aplin
Summary: Effective therapeutic options are lacking for uveal melanoma (UM) patients with metastasis. This study identified BRCA1-associated protein 1 (BAP1) mutations as being associated with reprogrammed cell metabolism, potentially providing a therapeutic opportunity for BAP1 mutant UM patients.
Article
Multidisciplinary Sciences
Jagadish C. Ghosh, Michela Perego, Ekta Agarwal, Irene Bertolini, Yuan Wang, Aaron R. Goldman, Hsin-Yao Tang, Andrew Kossenkov, Catherine J. Libby, Lucia R. Languino, Edward F. Plow, Annamaria Morotti, Luisa Ottobrini, Marco Locatelli, David W. Speicher, M. Cecilia Caino, Joel Cassel, Joseph M. Salvino, Marie E. Robert, Valentina Vaira, Dario C. Altieri
Summary: The study reveals that many human tumors have reduced levels of Mic60, an essential scaffold of mitochondrial structure, which leads to the disruption of mitochondrial integrity. Surprisingly, these tumors show decreased cell proliferation, resistance to cell death, and activation of a gene expression program related to innate immunity and cytokine/chemokine signaling. This process induces epithelial-mesenchymal transition, tumor cell movement, and promotes metastatic dissemination.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Michela Perego, Shuyu Fu, Yingjiao Cao, Andrew Kossenkov, Meng Yao, Kevin Alicea-Torres, Wangkai Liu, Zhilong Jiang, Zhihong Chen, Serge Y. Fuchs, Jie Zhou, Dmitry Gabrilovich
Summary: The transient appearance of immune suppressive PMNs-MDSCs in newborns is important for protection against inflammation related to gut microbiota. The inhibition of the IFN1 pathway plays a major role in regulating the suppressive activity of PMNs-MDSCs during the first few weeks of life. Furthermore, lactoferrin signaling through its receptor, low-density lipoprotein receptor-related protein 2, is required for PMNs-MDSCs' immune suppressive function.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Review
Oncology
Michael Xu, Latese Evans, Candice L. Bizzaro, Fabio Quaglia, Cecilia E. Verrillo, Li Li, Julia Stieglmaier, Matthew J. Schiewer, Lucia R. Languino, William K. Kelly
Summary: Despite therapeutic advances in prostate cancer treatment, metastatic castration-resistant prostate cancer remains a challenge. Highly expressed proteins STEAP1-4 have been identified as significant drivers of prostate cancer aggressiveness and metastasis. However, their other biological functions and understanding of heterotrimers and homotrimers are limited. This review highlights the importance of further research on the role of STEAP1-4 in prostate cancer and their potential clinical applications.
Article
Multidisciplinary Sciences
Fabio Quaglia, Shiv Ram Krishn, Khalid Sossey-Alaoui, Priyanka Shailendra Rana, Elzbieta Pluskota, Pyung Hun Park, Christopher D. Shields, Stephen Lin, Peter McCue, Andrew Kossenkov, Yanqing Wang, David W. Goodrich, Sheng-Yu Ku, Himisha Beltran, William K. Kelly, Eva Corey, Maja Klose, Christine Bandtlow, Qin Liu, Dario C. Altieri, Edward F. Plow, Lucia R. Languino
Summary: This study reveals a novel pathway activated by αVβ3 that promotes NEPrCa differentiation. NgR2 associates with αVβ3 and promotes NED and anchorage-independent growth in PrCa cells. These findings provide important insights into the mechanistic understanding of PrCa progression towards a NE phenotype.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Dipakkumar R. Prajapati, Caitlin Molczyk, Abhilasha Purohit, Sugandha Saxena, Reegan Sturgeon, Bhavana J. Dave, Sushil Kumar, Surinder K. Batra, Rakesh K. Singh
Summary: Pancreatic cancer (PC) has a poor prognosis, and targeting CXCR2/1 using small molecule inhibitors shows promise in inhibiting PC growth, angiogenesis, and metastasis. In this study, the therapeutic utility of the CXCR2/1 antagonist SCH-479833 was evaluated in different PC murine models, demonstrating antitumor and anti-metastatic effects. CXCR2/1 antagonist treatment inhibited tumor cell proliferation, migration, angiogenesis, and neutrophil recruitment, while promoting apoptosis, fibrosis, tumor necrosis, and extramedullary hematopoiesis. These findings suggest that selectively targeting CXCR2/1 with small molecule inhibitors is a promising therapeutic approach for PC.
Article
Oncology
Katelyn D. Miller, Seamus O'Connor, Katherine A. Pniewski, Toshitha Kannan, Reyes Acosta, Gauri Mirji, Sara Papp, Michael Hulse, Dzmitry Mukha, Sabina I. Hlavaty, Kelsey N. Salcido, Fabrizio Bertolazzi, Yellamelli V. V. Srikanth, Steven Zhao, Kathryn E. Wellen, Rahul S. Shinde, Daniel T. Claiborne, Andrew Kossenkov, Joseph M. Salvino, Zachary T. Schug
Summary: Blocking ACSS2 enzyme remodels acetate metabolism in cancer cells, allowing acetate to be used by tumor-infiltrating lymphocytes, enhancing their effector function and promoting antitumor immunity.
Article
Oncology
Sugandha Saxena, Caitlin Molczyk, Abhilasha Purohit, Evie Ehrhorn, Paran Goel, Dipakkumar R. Prajapati, Pranita Atri, Sukhwinder Kaur, Paul M. Grandgenett, Michael A. Hollingsworth, Surinder K. Batra, Rakesh K. Singh
Summary: The study found that different CXCR2 ligands are highly expressed in pancreatic cancer compared to normal tissue, with CXCL5 expression being associated with poor patient survival. It was also observed that cell lines derived from metastatic sites show higher expression levels of CXCL2, 3, and 5. Immunohistochemistry analysis further showed positive staining for CXCL1, 3, and 8 in pancreatic cancer tumors, indicating their potential as diagnostic biomarkers. The expression of mouse CXCL1, 3, and 5 was also found to increase in pre-cancerous lesions and metastasis tissues.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
