Article
Oncology
Sara Magri, Beatrice Musca, Laura Pinton, Elena Orecchini, Maria Laura Belladonna, Ciriana Orabona, Camilla Bonaudo, Francesco Volpin, Pietro Ciccarino, Valentina Baro, Alessandro Della Puppa, Susanna Mandruzzato
Summary: This study investigates the immune-suppressive activity of tumor-associated macrophages (TAMs) in the glioblastoma tumor microenvironment (TME). Researchers found that sustained iron metabolism and immune-suppressive activity in TAMs were correlated. They also discovered that blocking the central enzyme heme oxygenase-1 (HO-1) could reverse the tolerogenic activity of TAMs. Additionally, the activation status of T cells affected the expression of PD-L1 and the activity of IDO1, with both being upregulated in the presence of activated T cells. These findings highlight the crucial role of HO-1 in TAMs' immune-suppressive activity and suggest the feasibility of reprogramming TAMs for immune surveillance restoration.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Cell Biology
Jianfeng Huang, Binbin Wan, Sha Li, Gang Liu, Qingfeng Pang, Jia Wu, Erwen Bao, Changling Sun, Yan Qin, Kewei Wang, Fei Yang, Yaxian Wu, Fuzheng Zhang, Bo Yang
Summary: High expression of HO-1 and CD163 in TAMs was associated with poor survival in nasopharyngeal carcinoma (NPC). HO-1 exhibited superior ability in predicting survival compared with CD163, suggesting it may serve as a promising target for individualized therapy in NPC.
Review
Immunology
Kim Ngan Luu Hoang, Joanne E. Anstee, James N. Arnold
Summary: HO-1 is an inducible intracellular enzyme expressed in various cancers to promote tumor progression through intracellular and extracellular mechanisms. Its catabolites provide antioxidant, anti-apoptotic, and cytoprotective effects within cells, while also influencing the wider tumor microenvironment to promote processes like angiogenesis, metastasis, anti-inflammation, and immune suppression. Pharmacological inhibition of HO-1 shows promise in inhibiting metastasis and promoting anti-tumor immune responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Joseana de Oliveira, Marina B. Denadai, Diego L. Costa
Summary: Heme oxygenase-1 (HO-1) plays a crucial role in iron metabolism and has the potential to modulate immunity and inflammation through regulating cellular oxidation reactions and the expression of inflammation-related proteins.
Review
Immunology
Sen Yang, Jing Ouyang, Yanqiu Lu, Vijay Harypursat, Yaokai Chen
Summary: Iron metabolism is essential for the survival of humans and microorganisms, and heme oxygenase-1 (HO-1) plays a significant role in this process. Recent studies have shown that HO-1 has a dual role in tuberculosis, acting as both a cytoprotective molecule and potentially facilitating the survival and dissemination of Mycobacterium tuberculosis. This understanding of the interplay between HO-1, tuberculosis, and the host is crucial for the development of potential strategies to modulate HO-1 and iron metabolism.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Dandan Sheng, Wei Ma, Rui Zhang, Lei Zhou, Qiaodan Deng, Juchuanli Tu, Weilong Chen, Fuchuang Zhang, Nailong Gao, Mengxue Dong, Dong Wang, Fengkai Li, Yin Liu, Xueyan He, Shengzhong Duan, Lixing Zhang, Tong Liu, Suling Liu
Summary: Our study reveals that DTX-induced CCL3 triggers proinflammatory macrophage polarization and facilitates phagocytosis of cancer cells. CCL3 induction in combination with DTX may provide a promising therapeutic rationale for increasing DTX chemosensitivity in breast cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Immunology
Francesca Maria Consonni, Augusto Bleve, Maria Grazia Totaro, Mariangela Storto, Paolo Kunderfranco, Alberto Termanini, Fabio Pasqualini, Chiara Ali, Chiara Pandolfo, Francesco Sgambelluri, Giulia Grazia, Mario Santinami, Andrea Maurichi, Massimo Milione, Marco Erreni, Andrea Doni, Marco Fabbri, Laura Gribaldo, Eliana Rulli, Miguel Parreira Soares, Valter Torri, Roberta Mortarini, Andrea Anichini, Antonio Sica
Summary: This study identifies a distinct subset of TAMs with high rates of heme catabolism by HO-1, playing a critical role in shaping a prometastatic tumor microenvironment and favoring immunosuppression, angiogenesis and epithelial-to-mesenchymal transition. These TAMs originate from BM precursors, accumulate in the blood of tumor bearers, and preferentially localize at the invasive margin through Nrf2 activation and NF-kappa B1-CSF1R-C3aR axis coordination. Hindering their recruitment or deletion of HO-1 inhibits metastasis formation and enhances anticancer immunotherapy, making them a potential antimetastatic target and prognostic blood marker.
Article
Pharmacology & Pharmacy
Yen-Chang Chen, Jia-Hong Chen, Cheng-Fang Tsai, Chen-Teng Wu, Miao-Hsiang Wu, Pei-Chun Chang, Wei-Lan Yeh
Summary: The study found that nicardipine can inhibit the migration and colony formation of breast cancer cells, and increase the expression of Nrf2 and HO-1. The reduction of matrix metalloproteinase-9 by nicardipine is regulated by Nrf2/HO-1 axis and its catalytic end products.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Food Science & Technology
Yen-Chang Chen, Yu-Kai Cheng, Jia-Hong Chen, Cheng-Fang Tsai, Tsung-Kai Wang, Chen-Yun Wu, Pei-Chun Chang, Wei-Lan Yeh
Summary: This research investigates the effects of cardamonin on pulmonary inflammation. The results suggest that cardamonin has anti-inflammatory and anti-oxidative properties against PMA-induced pulmonary inflammation. It activates the Nrf2/HO-1 axis and reduces pro-inflammatory responses in alveolar macrophages.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Oncology
Iman M. Ahmad, Alicia J. Dafferner, Kelly A. O'Connell, Kamiya Mehla, Bradley E. Britigan, Michael A. Hollingsworth, Maher Y. Abdalla
Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis. Tumor hypoxia promotes tumor progression, malignancy, and therapy resistance in PDAC. The study demonstrates that nab-paclitaxel-gemcitabine (NPG) and a hypoxic tumor microenvironment up-regulate heme oxygenase-1 (HO-1), providing a survival advantage for tumors.
Article
Medicine, Research & Experimental
Taewoo Kim, Jessica Johnston, Sonia Castillo-Lluva, Francisco J. Cimas, Stephen Hamby, Santiago Gonzalez-Moreno, Pedro Villarejo-Campos, Alison H. Goodall, Guillermo Velasco, Alberto Ocana, Munitta Muthana, Endre Kiss-Toth
Summary: TRIB1 plays a key role in regulating the phenotype and function of tumor-associated macrophages in breast cancer. High expression of TRIB1 is associated with a better response to chemotherapy and improved patient survival. Both overexpression and knockout of myeloid Trib1 promote mouse breast tumor growth, but through different molecular mechanisms.
Article
Biochemistry & Molecular Biology
Lucia Longhitano, Giuseppe Broggi, Sebastiano Giallongo, Maria Failla, Lidia Puzzo, Teresio Avitabile, Daniele Tibullo, Alfio Distefano, Valeria Pittala, Michele Reibaldi, Guido Nicola Zanghi, Antonio Longo, Andrea Russo, Rosario Caltabiano, Giovanni Li Volti, Nicolo Musso
Summary: The study revealed the important role of HO-1 in regulating uveal melanoma progression, with an increase of HO-1 promoting cellular proliferation and wound healing ability of tumor cells, suggesting HO-1 protein expression may serve as a potential prognostic and therapeutic factor in UM patients.
Review
Biochemistry & Molecular Biology
Maria G. Detsika, Elias A. Lianos
Summary: Heme oxygenase-1 has a new cytoprotective role by regulating the complement control protein, which helps prevent kidney injury. Targeting HO-1 induction in specific cells could be a novel approach to attenuate complement-dependent kidney diseases.
Article
Oncology
Jonathan L. Hecht, Monika Janikova, Reeham Choudhury, Fong Liu, Giacomo Canesin, Lubica Janovicova, Eva Csizmadia, Elisa M. Jorgensen, Katharine M. Esselen, Peter Celec, Kenneth D. Swanson, Barbara Wegiel
Summary: This study investigates the link between endometriosis and ovarian clear cell cancer (OCCC) and proposes that altered heme metabolism and the presence of oxidative stress in the immune niche may drive OCCC development. The study also highlights the role of macrophages in this process and identifies elevated levels of HO-1 as a potential biomarker for inflammation.
Article
Biochemistry & Molecular Biology
Tanima Chatterjee, Itika Arora, Lilly Underwood, Anastasiia Gryshyna, Terry L. Lewis, Juan Xavier Masjoan Juncos, Burel R. Goodin, Sonya Heath, Saurabh Aggarwal
Summary: A large number of people with HIV experience chronic widespread pain. This study found that high heme or low HO-1 levels caused mast cell activation and release of pain mediators in both HIV patients and animal models. CO donation inhibited mast cell degranulation and reduced pain sensitivity in the animal models.
Article
Hematology
Xu Cao, Yingyu Wang, Wencan Zhang, Xiancai Zhong, E. Gulsen Gunes, Jessica Dang, Jinhui Wang, Alan L. Epstein, Christiane Querfeld, Zuoming Sun, Steven T. Rosen, Mingye Feng
Summary: This study identifies a novel and effective strategy for treating late-stage non-Hodgkin lymphoma by remodeling the tumor microenvironment to enhance the tumoricidal effects of tumor-associated macrophages (TAMs). The study also characterizes TAM subgroups that determine the efficiency of lymphoma phagocytosis in the tumor microenvironment, which can be potential therapeutic targets to unleash the antitumor activities of macrophages.
Article
Biochemistry & Molecular Biology
Soma Saeidi, Su-Jung Kim, Yanymee N. Guillen-Quispe, Achanta Sri Venkata Jagadeesh, Hyeong-Jun Han, Seung Hyeon Kim, Xiancai Zhong, Juan-Yu Piao, Seong-Jin Kim, Joon Jeong, Yun Jin Shin, Yoon Jin Cha, Han-Byoel Lee, Wonshik Han, Sang-Hyun Min, Wang Tian, Hiroshi Kitamura, Young-Joon Surh
Summary: Pin1 is frequently overexpressed in various types of malignancy, including triple-negative breast cancer, and plays a role in stabilizing and activating Nrf2 by competing with Keap1 for Nrf2 binding, thus promoting breast cancer progression. Through its interaction with phosphorylated Nrf2 and Keap1 residues, Pin1 alters the stability and function of Nrf2, leading to the accumulation of Nrf2 in the nucleus and contributing to breast cancer development and progression.
Article
Gastroenterology & Hepatology
Shin-Young Gwak, Su-Jung Kim, Jeongmin Park, Seung Hyeon Kim, Yeonsoo Joe, Ha-Na Lee, Wonki Kim, Ishrat Aklima Muna, Hye-Kyung Na, Hun Taeg Chung, Young-Joon Surh
Summary: This study demonstrates the crucial role of HO-1 in resolving experimentally induced colitis by modulating macrophage polarization. Inhibiting HO-1 hindered the resolution of intestinal inflammation, while phagocytosis of apoptotic colonic epithelial cells promoted the expression of HO-1 and Nrf2, leading to increased CD206-expressing macrophages. Additionally, HO-1 inhibition reduced the proportion of efferocytic BMDMs expressing CD36.
Article
Biochemistry & Molecular Biology
Jie Zheng, Do-Hee Kim, Xizhu Fang, Seong Hoon Kim, Soma Saeidi, Su-Jung Kim, Young-Joon Surh
Summary: The study suggests that sulforaphane may stimulate tumor progression in hepatocarcinogenesis rather than preventing it.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Achanta Sri Venakata Jagadeesh, Xizhu Fang, Seong Hoon Kim, Yanymee N. Guillen-Quispe, Jie Zheng, Young-Joon Surh, Su-Jung Kim
Summary: HO-1 is a stress-responsive enzyme with antioxidant and anti-inflammatory functions. It degrades heme and produces carbon monoxide and bilirubin. However, recent research has shown that upregulation of HO-1 promotes cancer progression, independent of its catalytic activity. These non-canonical functions are associated with HO-1's interaction with other proteins and its post-translational modifications.
JOURNAL OF CANCER PREVENTION
(2022)
Article
Cell Biology
Bastien Dolfi, Alexandre Gallerand, Maria M. Firulyova, Yingzheng Xu, Johanna Merlin, Adelie Dumont, Alexia Castiglione, Nathalie Vaillant, Sandrine Quemener, Heidi Gerke, Marion I. Stunault, Patricia R. Schrank, Seung-Hyeon Kim, Alisha Zhu, Jie Ding, Jerome Gilleron, Virginie Magnone, Pascal Barbry, David Dombrowicz, Christophe Duranton, Abdelilah Wakkach, Claudine Blin-Wakkach, Burkhard Becher, Sophie Pagnotta, Rafael J. Arguello, Pia Rantakari, Svetoslav Chakarov, Florent Ginhoux, Konstantin Zaitsev, Ki-Wook Kim, Laurent Yvan-Charvet, Rodolphe R. Guinamard, Jesse W. Williams, Stoyan Ivanov
Summary: This study reveals the diversity, origin, and function of adrenal gland macrophages using single-cell RNA sequencing and genetic models. The study identifies monocyte-derived and embryonically seeded adrenal gland macrophage populations, as well as a subset of macrophages in females with low MHC II expression. The distribution and functions of adrenal gland macrophages show sex-dimorphic patterns, with MHC IIlow macrophages located at the cortico-medullary junction. Depletion of adrenal gland macrophages leads to altered tissue homeostasis, modulated lipid metabolism, and decreased local aldosterone production during stress exposure.
Article
Multidisciplinary Sciences
Wencan Zhang, Xu Cao, Xiancai Zhong, Hongmin Wu, Mingye Feng, Yousang Gwack, Isakov Noah, Zuoming Sun
Summary: This study reveals the important role of steroid nuclear receptor coactivator 2 (SRC2) in regulating the differentiation of regulatory T cells (T-regs). Deficiency of SRC2 in T cells leads to defective T-reg differentiation and the development of autoimmune phenotypes. SRC2 promotes T-reg differentiation through the regulation of Nr4a2 and Foxp3 expression.
Article
Multidisciplinary Sciences
Phoenix Toboz, Mehdi Amiri, Negar Tabatabaei, Catherine R. Dufour, Seung Hyeon Kim, Carine Fillebeen, Charles E. Ayemoba, Arkady Khoutorsky, Manfred Nairz, Lijian Shao, Kostandin V. Pajcini, Ki-Wook Kim, Vincent Giguere, Regiana L. Oliveira, Marco Constante, Manuela M. Santos, Carlos R. Morales, Kostas Pantopoulos, Nahum Sonenberg, Sandra Pinho, Soroush Tahmasebi
Summary: GCN2 plays a crucial role in controlling erythrocyte clearance and iron recycling during stress, with liver macrophages serving as the primary cell type involved in mediating these effects.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Xiancai Zhong, Hongmin Wu, Wencan Zhang, Yousang Gwack, Weirong Shang, Kyle O. Lee, Noah Isakov, Zhiheng He, Zuoming Sun
Summary: This research reveals that RORyt not only regulates the differentiation of TH17 cells, but also plays a role in their effector function. By mutating K256R, which prevents ubiquitination of RORyt, the distinct functions of RORyt in TH17 differentiation and effector function can be separated.
Article
Medicine, Research & Experimental
Xizhu Fang, Yeon-Hwa Lee, Jeong-Hoon Jang, Su-Jung Kim, Seong Hoon Kim, Do-Hee Kim, Hye-Kyung Na, Kyung-Ok Kim, Jeong-Heum Baek, Young-Joon Surh
Summary: This study found that ARD1 stabilizes NRF2 by increasing its acetylation levels, thereby enhancing the oncogenic function of NRF2 in human colon cancer.
Article
Multidisciplinary Sciences
Wencan Zhang, Xu Cao, Xiancai Zhong, Hongmin Wu, Yun Shi, Mingye Feng, Yi-Chang Wang, David Ann, Yousang Gwack, Yate-Ching Yuan, Weirong Shang, Zuoming Sun
Summary: The study finds that the nuclear receptor coactivator SRC2 enhances CD4+ T cell activation by recruiting c-Myc and upregulating amino acid transporter Slc7a5, thereby stimulating immune responses. Mice deficient in SRC2 in T cells are resistant to EAE but susceptible to C. rodentium. SRC2fl/fl/CD4Cre mice display impaired T cell proliferation, cytokine production, and differentiation in vitro and in vivo. Therefore, SRC2 is essential for CD4+ T cell activation and could be a potential drug target for controlling CD4+ T cell-mediated autoimmunity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Oncology
Xiancai Zhong, Hongmin Wu, Ching Ouyang, Wencan Zhang, Yun Shi, Yi-Chang Wang, David K. Ann, Yousang Gwack, Weirong Shang, Zuoming Sun
Summary: This study reveals the role of nuclear receptor coactivator 2 (Ncoa2) in regulating CD8(+) T-cell function and tumor immune responses. Ncoa2 enhances mitochondrial function and T-cell activation, promoting CD8(+) T-cell-mediated immune responses against tumors. This research provides a theoretical basis for the development of Ncoa2-based therapies for cancer.
CANCER IMMUNOLOGY RESEARCH
(2023)
Article
Medicine, Research & Experimental
Shuting Cao, Yu-Wen Hung, Yi-Chang Wang, Yiyin Chung, Yue Qi, Ching Ouyang, Xiancai Zhong, Weidong Hu, Alaysia Coblentz, Ellie Maghami, Zuoming Sun, H. Helen Lin, David K. Ann
Summary: Attenuated host autophagy plays a role in inducing tumor rejection through reinforced adaptive immunity, while dietary glutamine supplementation promotes antitumor immunity by exposing differences in plasticity between cancer cells, CD8(+) T cells, and Tregs.
Article
Multidisciplinary Sciences
Xu Cao, Jing Chen, Bolei Li, Jessica Dang, Wencan Zhang, Xiancai Zhong, Chongkai Wang, Mustafa Raoof, Zuoming Sun, Jianhua Yu, Marwan G. Fakih, Mingye Feng
Summary: This study identifies paclitaxel as a universal adjuvant that enhances the efficacy of antibody-dependent cellular phagocytosis (ADCP) in multiple cancers. The researchers found that paclitaxel polarizes macrophages and enhances their phagocytic ability, leading to increased ADCP of cancer cells. Furthermore, the down-regulation of CSF1R in macrophages enhances the ADCP of cancer cells. These findings suggest a potent strategy for using conventional anticancer drugs to stimulate macrophage phagocytosis and enhance the therapeutic efficacy of clinical anticancer antibodies.