Editorial Material
Oncology
Stephanie L. Tzetzo, Scott I. Abrams
Summary: Macrophages are multi-functional immune cells that are present in normal or pathological tissues, including cancer tissues, but their ontogeny and transcriptional networks are often overlooked in immuno-oncology. Reprogramming macrophages therapeutically to maintain their tumoricidal activities could be crucial in cancer treatment.
Article
Chemistry, Multidisciplinary
Baicheng Wei, Jingmei Pan, Ruiting Yuan, Binfen Shao, Yi Wang, Xing Guo, Shaobing Zhou
Summary: A new cancer treatment strategy has been developed, where tumor-associated macrophage polarization therapy combined with ICD induced by low-dose chemotherapy drugs can significantly enhance the efficacy of immunotherapy.
Article
Chemistry, Multidisciplinary
Chao Wan, Yajie Sun, Yan Hu, Jing Huang, Lisen Lu, Yanan Gao, Huaduan Zi, Qianyuan He, Jinfeng Sun, Jonathan F. Lovell, Kunyu Yang, Honglin Jin
Summary: A therapeutic peptide hydrogel developed in this study effectively kills tumor cells, reshapes the tumor microenvironment, and enhances the efficacy of immune checkpoint blockade therapy, leading to prolonged survival.
Review
Chemistry, Multidisciplinary
Caiyan Zhao, Xiaoyu Pang, Zuo Yang, Sheng Wang, Hongzhang Deng, Xiaoyuan Chen
Summary: TAMs are key players in tumor progression and can be modulated using nanotechnology-based strategies, such as inhibiting their recruitment, depleting M2-polarized macrophages, and reprogramming them into M1-polarized macrophages. Nanoparticles can also be used to image TAMs for novel treatment options and therapy monitoring.
JOURNAL OF CONTROLLED RELEASE
(2022)
Review
Oncology
Giulia Marelli, Nicolo Morina, Federica Portale, Marta Pandini, Marta Iovino, Giusy Di Conza, Ping-Chih Ho, Diletta Di Mitri
Summary: Macrophages are key players in the immune system and their dysfunction can contribute to various diseases, including cancer. Lipid metabolism plays a role in macrophage activation and lipid accumulation can lead to pathogenic features. A subset of lipid-loaded macrophages, known as tumor-associated macrophages (TAMs), are involved in tumor growth and immune suppression.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Chemistry, Multidisciplinary
Huixiang Xiao, Xinxing Du, Zhenkeke Tao, Nan Jing, Shijia Bao, Wei-Qiang Gao, Baijun Dong, Yu-Xiang Fang
Summary: Tumor-associated macrophages (TAMs) inhibit ferroptosis in tumors by secreting taurine and promoting miR-181a-5p transport. This reciprocal interaction forms a positive feedback loop between tumor cells and TAMs, resulting in therapeutic resistance.
Article
Biotechnology & Applied Microbiology
Jia-Yin Chen, Xu-Yun Huang, Fei Lin, Qi You, Yu-Ting Xue, Bin Lin, Qing-Shui Zheng, Yong Wei, Xue-Yi Xue, Xiao-Dong Li, Dong-Ning Chen, Ning Xu
Summary: This study identified tumor-associated macrophages (TAMs) related molecular subtypes and developed a prognostic model for prostate cancer (PCa) based on TAMs. Three TAMs related molecular subtypes were identified, which were associated with prognosis, clinicopathological characteristics, PD-L1 expression levels, and tumor microenvironment. The developed prognostic model showed excellent predictive performance for biochemical recurrence-free survival in PCa.
Review
Oncology
Yifan Tan, Min Wang, Yang Zhang, Shengyang Ge, Fan Zhong, Guowei Xia, Chuanyu Sun
Summary: Macrophages are crucial innate immune cells that can promote tumor progression in the tumor microenvironment. Targeting tumor-associated macrophages has become a significant focus in cancer therapy due to their association with cancer advancement and poor prognosis.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shu Liu, Ying Ying Shen, Li Yang Yin, Jianghua Liu, Xuyu Zu
Summary: In the tumor microenvironment, tumor-associated macrophages (TAMs) and cancer cells have a complex interaction. TAMs can be reprogrammed by tumors, while TAMs also affect the growth of cancer cells. This review focuses on the changes in lipid metabolism between cancer cells and TAMs, providing potential targets for antitumor therapies.
DNA AND CELL BIOLOGY
(2023)
Article
Oncology
Guang Peng, Chao Wang, Hongru Wang, Min Qu, Keqin Dong, Yongwei Yu, Yuquan Jiang, Sishun Gan, Xu Gao
Summary: This study investigates the role of gankyrin in the progression and ADT resistance of prostate cancer through tumor cell-TAM interactions. Gankyrin is found to be a reliable prognostic indicator and therapeutic target for prostate cancer patients. Mechanistically, gankyrin recruits and upregulates NONO expression, leading to increased AR expression and subsequent HMGB1 transcription and secretion. HMGB1 promotes the recruitment and activation of TAMs, which in turn secrete IL-6 to promote prostate cancer progression, ADT resistance, and gankyrin expression via STAT3, thus forming a positive feedback loop.
Review
Oncology
Fahim Ahmad, Murali Krishna Cherukuri, Peter L. Choyke
Summary: While low-risk localized prostate cancer has a good prognosis with effective treatments, metastatic prostate cancer remains incurable and treatment resistance is a major issue. Resistance is primarily driven by tumor heterogeneity, altered genetic signatures, and metabolic reprogramming enabling tumors to adapt to drugs. Understanding prostate cancer metabolism may offer insights into therapy-induced adaptive responses and more durable therapeutic outcomes.
BRITISH JOURNAL OF CANCER
(2021)
Review
Oncology
Liang Li, Si-Rui Ma, Zi-Li Yu
Summary: This article introduces the lipid metabolism of tumor-associated macrophages (TAMs) and its important role in tumorigenesis and immunotherapy. The origins and classifications of TAMs are summarized, and the currently available drugs and interventions are discussed, along with the challenges and possible solutions.
Review
Oncology
Chunxiao Li, Xiaofei Xu, Shuhua Wei, Ping Jiang, Lixiang Xue, Junjie Wang
Summary: Macrophages play a crucial role in the tumor microenvironment, where they can be polarized into tumor-associated macrophages (TAMs). The abundance of TAMs in tumors is closely linked with poor prognosis, leading to investigations into therapeutic strategies targeting TAMs. These strategies include inhibiting macrophage recruitment to tumors, repolarizing TAMs towards an anti-tumor phenotype, and inducing macrophage-mediated destruction of cancer cells. As tumor immunotherapy gains more importance, new anti-tumor strategies focusing on TAMs are being discussed.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Pharmacology & Pharmacy
Jana B. B. Lampe, Priyanka P. P. Desai, Amit K. K. Tripathi, Nirupama A. A. Sabnis, Zhe Chen, Amalendu P. P. Ranjan, Jamboor K. K. Vishwanatha
Summary: We developed cabazitaxel-loaded nanoparticles using PLGA and introduced a bone-targeting moiety on the surface. These nanoparticles showed the ability to inhibit EMT, invasion and migration in prostate cancer cells. Treatment with targeted cabazitaxel-loaded nanoparticles led to decreased expression of EMT marker, Vimentin, and increased expression of E-cadherin, resulting in suppressed cancer progression. Furthermore, phosphorylated Src and cofilin levels were affected, potentially impacting migration and invasion pathways. The nanoparticles also showed increased expression of p-120 catenin and inhibition in IL-8 expression. Overall, targeted cabazitaxel-loaded nanoparticles hold promise for treating bone-metastatic prostate cancer.
Article
Cell Biology
Hongwen Cao, Dan Wang, Renjie Gao, Yigeng Feng, Lei Chen
Summary: In this study, the effects of Qi Ling (QL), a traditional Chinese medicine, on paclitaxel resistance in prostate cancer cells were evaluated. It was found that QL treatment re-programmed tumor-associated macrophages (TAMs) and decreased paclitaxel resistance in prostate cancer cells by down-regulating M2 markers and suppressing IL-6/STAT3 signaling pathway.
Article
Immunology
Yanqin Du, Tanvi Khera, Benedikt Strunz, Katja Deterding, Daniel Todt, Norman Woller, Sophie Anna Engelskircher, Svenja Hardtke, Kerstin Port, Andrea Ponzetta, Eike Steinmann, Markus Cornberg, Julia Hengst, Niklas K. Bjorkstrom, Heiner Wedemeyer
Summary: This study comprehensively analyzed the phenotype and reinvigoration capacity of unconventional T cells (UTCs) in acute symptomatic HCV infection. It was found that MAIT cells showed reduced frequency, but remaining cells had near-normal phenotype in acute infection, although they exhibited significant dysfunction upon stimulation that persisted even after viral clearance.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Oncology
Rumi Lee, Jiexi Li, Jun Li, Chang-Jiun Wu, Shan Jiang, Wen-Hao Hsu, Deepavali Chakravarti, Peiwen Chen, Kyle A. LaBella, Jing Li, Denise J. Spring, Di Zhao, Y. Alan Wang, Ronald A. DePinho
Summary: This study identifies critical effectors in the maintenance of APC-deficient colorectal cancer and demonstrates the relationship between APC/WNT pathway and kynurenine pathway signaling. It further determines the tumor-associated macrophage biology in APC-deficient colorectal cancer, informing genotype-specific therapeutic targets and the use of TDO2 inhibitors.
Article
Urology & Nephrology
Marco Bandini, Giuseppe Basile, Massimo Lazzeri, Francesco Montorsi, Benedetta Valli, Sofia Balo, Guido Barbagli
Summary: This study evaluated the factors predicting recurrence after treatment and the best rescue option for patients failing buccal mucosa graft (BMG) urethroplasty. The findings showed that stricture length >= 5 cm was the only predictor of failure. Direct visual internal urethrotomy (DVIU) was a good option as a rescue treatment, but its success rate decreased with the number of treatments performed. On the other hand, open urethroplasty improved outcomes in most patients.
Letter
Oncology
Pier Paolo Avolio, Massimo Lazzeri, Nicolo Maria Buffi, Giovanni Lughezzani
Article
Immunology
Martha E. Haugstoyl, Martin Cornillet, Kristina Strand, Natalie Stiglund, Dan Sun, Laurence Lawrence-Archer, Iren D. Hjellestad, Ernesto Sparrelid, Christian Busch, Joran Hjelmesaeth, Jens K. Hertel, Andrea Ponzetta, Gunnar Mellgren, Johan Ferno, Niklas K. Bjorkstrom
Summary: Adipose tissue inflammation is a key factor in the development of obesity-related metabolic disorders, and there is emerging evidence suggesting the involvement of adipose tissue T cells in initiating pro-inflammatory signaling. However, there is limited data on human adipose tissue T cells in obesity, mainly due to the lack of specific markers to define tissue-resident T cell subsets. In this study, we used multicolor flow cytometry and RNA sequencing to thoroughly characterize T cells in both blood and adipose tissue, and identified distinct subsets of T cells associated with obesity, expressing activation markers CD26 and CCR5, as well as obesity-specific genes potentially involved in activating pro-inflammatory pathways such as ceramide signaling, autophagy, and IL-6 signaling. These findings enhance our understanding of the heterogeneity of T cells in adipose tissue and shed light on subsets that may contribute to obesity-related pathogenesis.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Paola Cattaneo, Michael G. B. Hayes, Nina Baumgarten, Dennis Hecker, Sofia Peruzzo, Galip S. Aslan, Paolo Kunderfranco, Veronica Larcher, Lunfeng Zhang, Riccardo Contu, Gregory Fonseca, Simone Spinozzi, Ju Chen, Gianluigi Condorelli, Stefanie Dimmeler, Marcel H. Schulz, Sven Heinz, Nuno Guimaraes-Camboa, Sylvia M. Evans
Summary: This study reveals that H3K79me2, a modification catalyzed by DOT1L, plays a specific role in regulating gene expression during cardiogenesis. It is important for left ventricle-specific genes during embryonic cardiogenesis and is involved in postnatal cardiomyocyte cell cycle withdrawal. Mechanistic analyses show that H3K79me2 in gene bodies and regulatory elements synergistically promote gene expression activated by DOT1L. Additionally, H3K79me2 in specific regulatory elements also contributes to silencing genes not usually expressed in cardiomyocytes.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Nina Cortese, Roberta Carriero, Marialuisa Barbagallo, Anna Rita Putignano, Guido Costa, Fabio Giavazzi, Fabio Grizzi, Fabio Pasqualini, Clelia Peano, Gianluca Basso, Sergio Marchini, Federico Simone Colombo, Cristiana Soldani, Barbara Franceschini, Luca Di Tommaso, Luigi Terracciano, Matteo Donadon, Guido Torzilli, Paolo Kunderfranco, Alberto Mantovani, Federica Marchesi
Summary: Two M4 markers associated with opposite clinical relevance were identified through single-cell analysis, indicating the importance of improved classification and prognostic classifiers for patients with colorectal liver metastasis.
CANCER IMMUNOLOGY RESEARCH
(2023)
Article
Oncology
Pat Gulhati, Aislyn Schalck, Shan Jiang, Xiaoying Shang, Chang-Jiun Wu, Pingping Hou, Sharia Hernandez Ruiz, Luisa Solis Soto, Edwin Parra, Haoqiang Ying, Jincheng Han, Prasenjit Dey, Jun Li, Pingna Deng, Emi Sei, Dean Y. Maeda, John A. Zebala, Denise J. Spring, Michael Kim, Huamin Wang, Anirban Maitra, Dirk Moore, Karen Clise-Dwyer, Y. Alan Wang, Nicholas E. Navin, Ronald A. DePinho
Summary: Pancreatic ductal adenocarcinoma (PDAC) is resistant to PD1 and CTLA4 immune checkpoint therapies. This study characterized the mechanisms of ICT resistance and identified effective therapeutic options. The combination of agonist 41BB and antagonist LAG3 ICT increased survival and antitumor immunity. Triple therapy with T cell-activating ICTs and a CXCR1/2 inhibitor resulted in durable complete responses. This provides a testable hypothesis for clinical testing in human PDAC.
Letter
Urology & Nephrology
Nicola Frego, Roberto Contieri, Pietro Diana, Stefano Mancon, Piergiuseppe Colombo, Massimo Lazzeri, Nicolo Maria Buffi, Paolo Casale, Rodolfo Hurle
Review
Biochemistry & Molecular Biology
Federica Portale, Diletta Di Mitri
Summary: Natural killer cells (NK) are innate lymphocytes with the ability to recognize and kill cancer cells, making them a promising candidate for cancer treatment. However, cancer can impair the function of NK cells, limiting their effectiveness in cell therapies. Extensive research has been conducted to understand the mechanisms of NK cell dysfunction in cancer and to find ways to enhance their anti-tumor function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Jiexi Li, Zhengdao Lan, Wenting Liao, James W. W. Horner, Xueping Xu, Jielin Liu, Yohei Yoshihama, Shan Jiang, Hong Seok Shim, Max Slotnik, Kyle A. A. LaBella, Chang-Jiun Wu, Kenneth Dunner Jr, Wen-Hao Hsu, Rumi Lee, Isha Khanduri, Christopher Terranova, Kadir Akdemir, Deepavali Chakravarti, Xiaoying Shang, Denise J. J. Spring, Y. Alan Wang, Ronald A. A. DePinho
Summary: Sex plays an important role in cancer incidence, spectrum, and outcomes, particularly in colorectal cancer (CRC) where men have higher metastases and mortality rates. A study using a murine CRC model revealed that oncogenic mutant KRAS (KRAS*) CRC in males showed higher metastases and worse outcomes. Further analysis found that the Y-chromosome gene histone demethylase KDM5D, driven by KRAS*-mediated activation of the STAT4 transcription factor, contributed to the sex differences in KRAS* CRC. Deletion of Kdm5d in cancer cells improved tight junction integrity, reduced invasiveness, and enhanced cancer cell killing by CD8(+) T cells. On the contrary, mice with a Kdm5d transgene had a higher propensity for invasive tumors. Therefore, the upregulation of Y chromosome KDM5D via KRAS*-STAT4 pathway disrupts cancer cell adhesion properties and tumor immunity, providing a potential therapeutic strategy for reducing metastasis risk in men with KRAS* CRC.
Article
Oncology
Cesare Saitta, Ilaria De Simone, Vittorio Fasulo, Marinella Corbetta, Stefano Duga, Chiara Chiereghin, Federico Simone Colombo, Alessio Benetti, Roberto Contieri, Pier Paolo Avolio, Alessandro Uleri, Alberto Saita, Giorgio Ferruccio Guazzoni, Rodolfo Hurle, Piergiuseppe Colombo, Nicolo Maria Buffi, Paolo Casale, Giovanni Lughezzani, Rosanna Asselta, Giulia Solda, Massimo Lazzeri
Summary: Liquid biopsy (LB) is increasingly being explored as a non-invasive method for detecting prostate cancer (PCa). This study aimed to determine the rate of patients who were able to collect seminal fluid and evaluate the efficiency of the protocol in collecting prostate-derived cells. The results showed that only one third of locally advanced PCa patients were able to donate seminal fluid, with younger age and lower prostate volume being favorable predictors for semen collection.
Article
Microbiology
Raffaella Parente, Maria Rita Fumagalli, Alessia Di Claudio, Cindy Lorena Cardenas Rincon, Marco Erreni, Damiano Zanini, Giacomo Iapichino, Alessandro Protti, Cecilia Garlanda, Roberto Rusconi, Andrea Doni
Summary: This study highlights the importance of the extracellular matrix (ECM) and hemostasis elements in triggering Staphylococcus aureus (S. aureus) biofilm formation. Fibrinogen (FG) plays a crucial role in adhesion and formation, while fibrinolysis inhibits biofilm formation and promotes an antibody-mediated defense response.
Meeting Abstract
Urology & Nephrology
Edoardo Beatrici, Roberto Contieri, Nicola Frego, Vittorio Fasulo, Pietro Diana, Marco Paciotti, Davide Maffei, Pier Paol Avolio, Alessandro Uleri, Cesare Saitta, Paola Arena, Giuseppe Chiarelli, Andrea Gobbo, Nicolo Maria Buffi, Massimo Lazzeri, Paolo Casale, Alberto Saita, Giorgio Guazzoni, Giovanni Lughezzani, Rodolfo Hurle
JOURNAL OF UROLOGY
(2022)