Review
Biochemistry & Molecular Biology
Rola El Sayed, Yolla Haibe, Ghid Amhaz, Youssef Bouferraa, Ali Shamseddine
Summary: Immunotherapy has revolutionized cancer treatment, but resistance to checkpoint inhibition remains a challenge due to factors such as immune-sensitive tumors becoming immune-resistant and tumor microenvironment contributing to immune-resistance. Understanding the complex metabolic networks within the tumor microenvironment controlling immune response is essential for developing effective therapeutic strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Balaraman Kalyanaraman
Summary: Black and Hispanic cancer patients have a higher incidence of cancer mortality. Many factors contribute to racial disparity, including socioeconomic differences and insufficient access to healthcare. Emerging research suggests that biological disparity in cancer outcomes may be related to distinct differences in the tumor immune microenvironment (TIME) and altered mitochondrial metabolism.
Article
Immunology
Neetu Saini, Sowmya Lakshminarayanan, Priyanka Kundu, Apurva Sarin
Summary: This study reveals that calcium uptake and mitochondrial metabolism play a crucial role in regulating the survival of regulatory T cells (Tregs) and Notch1 activity is a key factor in modulating these processes. By modulating cellular calcium dynamics, Notch1 regulates mitochondrial homeostasis and anti-apoptotic activity, thus impacting the survival of Tregs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Jorge Luis Galeano Nino, Hanrui Wu, Kaitlyn D. LaCourse, Andrew G. Kempchinsky, Alexander Baryiames, Brittany Barber, Neal Futran, Jeffrey Houlton, Cassie Sather, Ewa Sicinska, Alison Taylor, Samuel S. Minot, Christopher D. Johnston, Susan Bullman
Summary: The study investigates the interactions between tumor-associated microbiota and host cells in oral squamous cell carcinoma and colorectal cancer using in situ spatial-profiling technologies and single-cell RNA sequencing. The results show that the distribution of microbiota within the tumor is highly organized in microniches with immune and epithelial cell functions, promoting cancer progression.
Article
Chemistry, Multidisciplinary
Okan Tezcan, Asmaa Said Elshafei, Karina Benderski, Elena Rama, Maike Wagner, Diana Moeckel, Robert Pola, Michal Pechar, Tomas Etrych, Saskia von Stillfried, Fabian Kiessling, Ralf Weiskirchen, Steffen Meurer, Twan Lammers
Summary: Multidrug resistance (MDR) reduces the efficacy of chemotherapy by inducing drug efflux pumps and altering the tumor microenvironment (TME) composition, limiting drug delivery. Multidrug-resistant tumors displayed a more mesenchymal phenotype, increased collagen production, enriched TME, and enhanced vascular perfusion. Drug carriers accumulated more efficiently in resistant tumors but had a limited ability to penetrate the interstitium. Microenvironmental drug resistance affected liposomal doxorubicin performance more than free doxorubicin.
JOURNAL OF CONTROLLED RELEASE
(2023)
Review
Medicine, Research & Experimental
Rahul Bhattacharjee, Tanima Dey, Lamha Kumar, Sulagna Kar, Ritayan Sarkar, Mimosa Ghorai, Sumira Malik, Niraj Kumar Jha, Balachandar Vellingiri, Kavindra Kumar Kesari, Jose M. Perez de la Lastra, Abhijit Dey
Summary: This review discusses the causes, mechanisms, and potential therapeutic strategies for cisplatin resistance in cervical cancer. Strategies such as the use of nanocarriers, miRNA, CRISPR/Cas system, and combination therapy with chemotherapeutics show promise in overcoming drug resistance and improving the efficacy of cisplatin. Furthermore, the review examines the signaling network of cisplatin-resistant cells in cervical cancer and the impact of tumor microenvironment on drug resistance.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Immunology
Jie Xing, Changfeng Man, Yingzhao Liu, Zhengdong Zhang, Huiyong Peng
Summary: Tumor development is closely associated with the complex tumor microenvironment, which includes various cellular components and molecular signals. The effector functions of Th17 cells in the tumor microenvironment are regulated by different molecular signals, leading to their dual effects on tumor progression. Understanding the impact of the tumor microenvironment on Th17 cells can provide valuable insights for the development of tumor immunotherapy strategies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Hanxin Liu, Huifang Zhao, Yu Sun
Summary: The tumor microenvironment plays a major role in the malignancy and therapeutic resistance of cancer, with intercellular communication contributing to this process. Immune evasion, extracellular matrix remodeling, and therapy-induced senescence (TIS) all contribute to cancer resistance and disease progression. The senescence-associated secretory phenotype (SASP) of senescent cells drives inflammation and promotes tumor relapse and distant metastasis. selectively removing senescent cells may be a promising strategy to prevent drug resistance associated with the remodelled tumor microenvironment.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Oncology
Maud Plaschka, Valentin Benboubker, Maxime Grimont, Justine Berthet, Laurie Tonon, Jonathan Lopez, Myrtille Le-Bouar, Brigitte Balme, Garance Tondeur, Arnaud de la Fouchardiere, Lionel Larue, Alain Puisieux, Yenkel Grinberg-Bleyer, Nathalie Bendriss-Vermare, Bertrand Dubois, Christophe Caux, Stephane Dalle, Julie Caramel
Summary: This study reveals that ZEB1 expression in melanoma cells is associated with decreased CD8(+) T cell infiltration, leading to tumor immune evasion and resistance to immune checkpoint blockade. ZEB1 directly represses the secretion of T cell-attracting chemokines, such as CXCL10, and targeting ZEB1 may enhance the efficacy of immunotherapy in melanoma.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Yangyang Zhang, Lingxiu Zeng, Meng Wang, Zhenwei Yang, Hailin Zhang, Liping Gao, Ranran Zhang, Jialong Liu, Wenqing Shan, Ying Chang, Lan Liu, Qiu Zhao, Yong Li, Jing Liu
Summary: The study found that RIG-I plays an important role in the immunotherapy of colon cancer by maintaining the stability of PD-L1 to promote immune evasion. Silencing RIG-I increases the sensitivity of tumor cells to T cell killing and slows down the growth of colon tumors. High expression of RIG-I promotes tumor progression and enhances the sensitivity to PD-1 therapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Shiyao Jiang, Jingjing Huang, Hua He, Yueying Liu, Lu Liang, Xiaoyan Sun, Yi Li, Li Cong, Bei Qing, Yiqun Jiang
Summary: This study investigated the relationship between erlotinib resistance and stemness in lung adenocarcinoma. The key gene NCAPG2 was identified as playing a vital role in both stemness and erlotinib resistance in lung adenocarcinoma. These findings provide important insights for the treatment and prognosis of patients with lung adenocarcinoma.
Review
Cell Biology
Karla F. Corral-Jara, Goncalo Rosas da Silva, Nora A. Fierro, Vassili Soumelis
Summary: CD4 + T cell differentiation is controlled by gene regulatory and metabolic networks, with Th17 and Tregs playing crucial roles in cancer, influenced by the tumor microenvironment. The modeling of biological systems has emerged as a promising solution for understanding CD4 + T cell differentiation and cancer cell behavior better. Integration of mechanistic models with omics data can predict transcriptomic and metabolomic reprogramming of Th17 and Tregs cells for potential clinical applications, particularly in cancer immunotherapy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Xuan Zou, Xuan Lin, He Cheng, Yusheng Chen, Ruijie Wang, Mingjian Ma, Yu Liu, Zhengjie Dai, Yesboli Tasiheng, Yu Yan, Qinqin Hou, Fei Ding, Huan Chen, Xianjun Yu, Xu Wang, Chen Liu
Summary: This study systematically revealed the cellular properties and prognostic values of intratumoral TLSs in pancreatic ductal adenocarcinoma (PDAC) and described the potential impact of neoadjuvant treatment (NAT) on TLS development and function.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Immunology
Yuanyuan Pan, Wenjing Yang, Bo Tang, Xiaobo Wang, Qi Zhang, Weiping Li, Li Li
Summary: At the turn of the century, a unique subtype of T helper cells called Th17, which secretes IL-17, was discovered. The latest study found that Th17 cells have both positive and negative roles in regulating antitumor immune responses. Though the function of Th17 in the tumor microenvironment is still not well understood, recent studies have shown that this paradoxical dual role is closely related to the plasticity of Th17 cells. Further understanding of Th17 cells' characteristics in the tumor microenvironment could lead to novel therapeutic approaches for cancer treatment.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Aiping Zhang, Kai Miao, Heng Sun, Chu-Xia Deng
Summary: Tumor heterogeneity is a major cause of drug resistance and affects drug efficacy by shaping the tumor microenvironment and therapeutic targets. Understanding the impact of tumor heterogeneity on drug resistance is important for cancer treatment and patient prognosis.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Oncology
John S. Runge, Anna B. Brown, Tycel J. Phillips, Mark S. Kaminski, Shannon A. Carty, Ryan A. Wilcox
Summary: This study evaluated the potential utility of telemedicine initiatives for lymphoma patients undergoing immunochemotherapy. The findings show that most dose modifications were reductions and only a small number were based on physical exam findings. Importantly, no dose modifications were exclusively based on abnormal physical exam findings during a pre-infusion assessment. Thus, virtual visits may be a feasible option for lymphoma patients undergoing immunochemotherapy.
JOURNAL OF ONCOLOGY PHARMACY PRACTICE
(2023)
Article
Statistics & Probability
Jonathan P. Williams, Yuying Xie, Jan Hannig
Summary: This paper presents theoretical investigations on VAR models using the epsilon-admissible subsets (EAS) approach based on a generalized fiducial distribution, and proves the pairwise and strong graphical selection consistency in stable VAR(1) models. It also demonstrates empirically that this approach is effective in high-dimensional settings.
CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE
(2023)
Meeting Abstract
Hematology
Luis O. Correa, Rich Lee, Alexander Dils, Aditi Vijendra, Shannon A. Carty
Article
Oncology
Gaopeng Li, Jae Eun Choi, Ilona Kryczek, Yilun Sun, Peng Liao, Shasha Li, Shuang Wei, Sara Grove, Linda Vatan, Reagan Nelson, Grace Schaefer, Steven G. Allen, Kamya Sankar, Leslie A. Fecher, Mishal Mendiratta-Lala, Timothy L. Frankel, Angel Qin, Jessica J. Waninger, Alangoya Tezel, Ajjai Alva, Christopher D. Lao, Nithya Ramnath, Marcin Cieslik, Paul W. Harms, Michael D. Green, Arul M. Chinnaiyan, Weiping Zou
Summary: Immune checkpoint blockade can have durable responses against cancer, but some patients experience rapid cancer progression during immunotherapy. The mechanism behind how tumors accelerate their progression during immune checkpoint blockade is not well understood. In preclinical models, immune checkpoint blockade can cause hyperprogressive disease. Interestingly, patients with hyperprogressive disease but not complete response exhibit elevated levels of tumor fibroblast growth factor 2 and β-catenin signaling. T cell-derived interferon γ promotes tumor fibroblast growth factor 2 signaling, suppressing PKM2 activity and decreasing NAD+ levels, which leads to enhanced β-catenin acetylation and reprogramming of tumor stemness. Targeting the interferon γ-PKM2-β-catenin axis can prevent hyperprogressive disease in preclinical models. These findings demonstrate the importance of the crosstalk between immunogenic, metabolic, and oncogenic pathways in immune checkpoint blockade-associated hyperprogressive disease.
Review
Biochemistry & Molecular Biology
Zeribe Chike Nwosu, Mun Gu Song, Marina Pasca di Magliano, Costas A. A. Lyssiotis, Sung Eun Kim
Summary: Cancer cells depend on specific extracellular nutrients for their metabolism and growth. SLC transporters play a crucial role in acquiring these nutrients and transferring intracellular nutrients. Understanding the function of SLC transporters in cancer could provide therapeutic targets for effective treatment.
Article
Chemistry, Multidisciplinary
Hyeoncheol Kim, Luke B. Villareal, Zhaoli Liu, Mohammad Haneef, Daniel M. Falcon, David R. Martin, Ho-Joon Lee, Michael K. Dame, Durga Attili, Ying Chen, James Varani, Jason R. Spence, Olga Kovbasnjuk, Justin A. Colacino, Costas A. Lyssiotis, Henry C. Lin, Yatrik M. Shah, Xiang Xue
Summary: This study reveals that transferrin receptor (TFRC) is induced by β-catenin activation driven by APC gene loss in colorectal cancer, and TFRC-mediated intratumoral iron accumulation enhances β-catenin signaling through tankyrase activation. Disruption of TFRC reduces colonic iron levels and iron-dependent tankyrase activity, leading to stabilization of AXIN2 and repression of the β-catenin/c-Myc/E2F Transcription Factor 1/DNA polymerase delta1 (POLD1) axis, causing increased DNA replication stress, DNA damage response, apoptosis, and reduced colon tumor growth. Iron chelation combined with DNA damaging agents further increases DNA damage response and reduces colon tumor cell growth. This discovery may offer new strategies for colorectal cancer therapy.
Article
Multidisciplinary Sciences
Mack B. Reynolds, Hanna S. Hong, Britton C. Michmerhuizen, Anna-Lisa E. Lawrence, Li Zhang, Jason S. Knight, Costas A. Lyssiotis, Basel H. Abuaita, Mary X. O'Riordan
Summary: Macrophage metabolic plasticity allows the redirection of electron transport for inflammation and host defense. Inflammatory activation leads to disassembly of Complex II and loss of succinate dehydrogenase subunit B through sequestration and selective mitophagy. The regulatory role of cardiolipin in coordinating Complex II function and inflammatory metabolic remodeling is demonstrated.
Article
Multidisciplinary Sciences
Jennifer Cable, Jeffrey C. Rathmell, Erika L. Pearce, Ping-Chih Ho, Marcia C. Haigis, Murad R. Mamedov, Meng-Ju Wu, Susan M. Kaech, Lydia Lynch, Mark A. Febbraio, Sagar P. Bapat, Hanna S. Hong, Weiping Zou, Yasmine Belkaid, Zuri A. Sullivan, Andrea Keller, Stefanie K. Wculek, Douglas R. Green, Catherine Postic, Ido Amit, Salvador Aznar Benitah, Russell G. Jones, Miguel Reina-Campos, Santiago Valle Torres, Semir Beyaz, Donal Brennan, Luke A. J. O'Neill, Rachel J. Perry, Dirk Brenner
Summary: Immunometabolism studies the relationship between metabolism and immunity, with a focus on the metabolic pathways within immune cells and the impact of immune cells on systemic metabolism. In the Keystone symposium on Immunometabolism at the Crossroads of Obesity and Cancer, experts presented recent research on the complex interplay between metabolism, immunity, and cancer, highlighting metabolic links between tumor cells and immune cells, the effects of diet, the microbiome, and obesity on immune system function and cancer, and new technologies to study the immune system and uncover novel metabolic pathways.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lingxin Zhu, Yi Tang, Xiao-Yan Li, Samuel A. Kerk, Costas A. Lyssiotis, Wenqing Feng, Xiaoyue Sun, Geoffrey E. Hespe, Zijun Wang, Marc P. Stemmler, Simone Brabletz, Thomas Brabletz, Evan T. Keller, Jun Ma, Jung-Sun Cho, Jingwen Yang, Stephen J. Weiss
Summary: Osteoclasts undergo transcriptional and metabolic changes during differentiation to acquire the cellular machinery for bone resorption. Zeb1, a zinc-finger transcriptional repressor, is found to play a role in osteoclast energy metabolism. By repressing a crucial enzyme involved in ATP buffering and mitochondrial respiration, Zeb1 controls the activity of osteoclasts and influences bone remodeling. This study reveals a novel Zeb1/MtCK1 axis that regulates bone resorption through metabolic control.
Article
Biochemistry & Molecular Biology
Brandon Chen, Nupur K. Das, Indrani Talukder, Rashi Singhal, Cristina Castillo, Anthony Andren, Joseph D. Mancias, Costas A. Lyssiotis, Yatrik M. Shah
Summary: PINK1 plays a positive role in colorectal cancer by promoting tumor survival and growth through regulating mitophagy and ferritinophagy pathways, which regulate intracellular iron availability and stability.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Cell Biology
Lingxin Zhu, Yi Tang, Xiao-Yan Li, Samuel A. Kerk, Costas A. Lyssiotis, Xiaoyue Sun, Zijun Wang, Jung-Sun Cho, Jun Ma, Stephen J. Weiss
Summary: The interaction between metalloproteins Mmp9 and Mmp14 and carbohydrate-binding protein galectin-3 plays a critical role in osteoclast-mediated bone resorption. The ability of Mmp9 and Mmp14 to degrade galectin-3 on the cell surface depends on its binding protein Lrp-1. These findings reveal a previously unrecognized galectin-3/Lrp1 axis that regulates both the transcriptional programs and intracellular signaling cascades essential for osteoclast function.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Zeribe C. Nwosu, Matthew H. Ward, Peter Sajjakulnukit, Pawan Poudel, Chanthirika Ragulan, Steven Kasperek, Megan Radyk, Damien Sutton, Rosa E. Menjivar, Anthony Andren, Juan J. Apiz-Saab, Zachary Tolstyka, Kristee Brown, Ho-Joon Lee, Lindsey N. Dzierozynski, Xi He, P. S. Hari, Julia Ugras, Gift Nyamundanda, Li Zhang, Christopher J. Halbrook, Eileen S. Carpenter, Jiaqi Shi, Leah P. Shriver, Gary J. Patti, Alexander Muir, Marina Pasca di Magliano, Anguraj Sadanandam, Costas A. Lyssiotis
Summary: Pancreatic ductal adenocarcinoma (PDA) is a highly resistant and lethal disease, driven by a complex tumor microenvironment, low vascularity, and metabolic aberrations. This study reveals that uridine is utilized as a fuel by PDA cells under glucose-deprived conditions. Uridine is metabolized by uridine phosphorylase 1 (UPP1) to support central carbon metabolism and promote survival and proliferation in nutrient-restricted PDA cells. UPP1 expression is regulated by KRAS-MAPK signaling and is correlated with poor survival in PDA patients. Moreover, UPP1 deletion impairs uridine utilization and inhibits tumor growth in mouse models. These findings suggest a novel metabolic axis for PDA therapy.
Meeting Abstract
Oncology
Yousef Zakharia, Eric A. Singer, Satwik Acharyya, Rohan Garje, Monika Joshi, David J. Peace, Veera Baladandayuthapani, Claudia Laancette, Ilona Kryczek, Weiping Zou, Ajjai Shivaram Alva
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Mathematics, Applied
Anna Little, Yuying Xie, Qiang Sun
Summary: This paper provides a theoretical framework for analyzing the quality of embedded samples produced by classical multidimensional scaling. It proposes scaling conditions that allow classical multidimensional scaling followed by a distance-based clustering algorithm to recover the cluster labels of all samples. Simulation studies and applications in cancer gene-expression data, single-cell RNA sequencing data, and natural language data provide strong support for the methodology and theory.
INFORMATION AND INFERENCE-A JOURNAL OF THE IMA
(2023)
