Review
Biochemistry & Molecular Biology
Brian S. M. Munansangu, Colin Kenyon, Gerhard Walzl, Andre G. Loxton, Leigh A. Kotze, Nelita du Plessis
Summary: Immunometabolism investigates the interaction between the immune system and metabolic pathways, with small molecules targeting specific pathways to alter immune responses for potential therapeutic interventions. The metabolic reprogramming of MDSC in diseases like cancer contributes to immunosuppression, highlighting the importance of understanding and targeting these pathways in diseases such as tuberculosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Antero Salminen
Summary: Alzheimer's disease is a progressive neurodegenerative disease that causes irreversible cognitive impairment and dementia. Hypoxia and inflammation play important roles in AD pathology, with an enhanced immunosuppression state closely associated with AD pathogenesis.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Review
Cell Biology
Francesca Hofer, Gianna Di Sario, Chiara Musiu, Silvia Sartoris, Francesco De Sanctis, Stefano Ugel
Summary: Research has shown that myeloid-derived suppressor cells play a crucial role in immune regulation within the tumor microenvironment, with their metabolic pathways and functions being essential for cancer progression.
Article
Oncology
Utku Horzum, Digdem Yoyen-Ermis, Ekim Z. Taskiran, Kerim Bora Yilmaz, Erhan Hamaloglu, Derya Karakoc, Gunes Esendagli
Summary: In cancer patients, a specific subpopulation of monocytes expressing CD66b was identified in the circulation. These monocytes displayed high phagocytic activity, matrix adhesion, and migration, and provided costimulation for T cell proliferation and IFN-gamma secretion without suppressing T cell responses. They represent a novel myeloid subpopulation which lacks immune regulatory influences and shows enhanced proinflammatory capacities.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Review
Pharmacology & Pharmacy
Taravat Khodaei, Sahil Inamdar, Abhirami P. Suresh, Abhinav P. Acharya
Summary: Drug delivery vehicles have had a significant impact on cancer immunotherapies, inspiring the development of successful companies and clinical products. These vehicles not only modulate the function of immune cells, but also their metabolism. Intervention strategies that directly modulate the energy metabolism of immune cells have generated great excitement and potential for robust cancer immune responses.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Yichen Li, Qian Zhang, Mandi Wu, Peidong Zhang, Liang Huang, Xiaolin Ai, Zhengnan Yang, Qiuhong Shen, Yiran Wang, Ping Wang, Shengtao Zhou, Ming-Liang He
Summary: A study has found that a LncRNA associated with ovarian cancer metastasis, LncOVM, is highly correlated with poor prognosis and survival. LncOVM interacts with and stabilizes PPIP5K2, promoting the secretion of complement C5 from ovarian cancer cells, which then attracts myeloid-derived suppressor cells (MDSCs) infiltration in the tumor microenvironment (TME) to facilitate metastasis. Targeting the LncOVM-PPIP5K2-complement axis can inhibit MDSC infiltration and restore the suppression of tumorigenesis and metastasis.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Oncology
Laxminarasimha Donthireddy, Prashanthi Vonteddu, Tushar Murthy, Taekyoung Kwak, Rukiye-Nazan Eraslan, Joseph R. Podojil, Adam Elhofy, Michael T. Boyne, John J. Puisis, Filippo Veglia, Surya S. Singh, Farokh Dotiwala, Luis J. Montaner, Dmitry Gabrilovich
Summary: In this study, the researchers evaluated the effectiveness of negatively charged bio-degradable nanoparticles called ONP-302 in inhibiting tumor growth. The results showed that treatment with ONP-302 significantly delayed tumor growth in immunocompetent mice in three different tumor models. ONP-302 also caused a shift in gene expression in tumor-associated macrophages (TAMs) towards the pro-inflammatory M1 type and inhibited the expression of genes associated with the pro-tumorigenic function of cancer-associated fibroblasts (CAFs). This study supports the further development of ONP-302 as a potential anti-cancer therapeutic agent.
Article
Gastroenterology & Hepatology
Megan T. Hoffman, Samantha B. Kemp, Daniel J. Salas-Escabillas, Yaqing Zhang, Nina G. Steele, Stephanie The, Daniel Long, Simone Benitz, Wei Yan, Robert F. Margolskee, Filip Bednar, Marina Pasca di Magliano, Hui-Ju Wen, Howard C. Crawford
Summary: This study demonstrates that inhibiting GNAT3 can increase the release of tumor-promoting cytokines, alter the MDSC population, and promote the progression of metastatic PDA.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Review
Endocrinology & Metabolism
Elham Samami, Elahe Aleebrahim-Dehkordi, Mehdi Mohebalizadeh, Shakila Yaribash, Amene Saghazadeh, Nima Rezaei
Summary: This article reviews the roles of cancer immunity, gut microbiota, and inosine in cancer immunometabolism. The gut microbiota influences both antitumor immunity and protumor immune signaling, while inosine is involved in immune checkpoint inhibition therapeutic response and T-cell metabolism. Further research is needed to explore the potential of inosine as a cancer immunometabolism therapy.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Immunology
Steven H. Sun, Brooke Benner, Himanshu Savardekar, Gabriella Lapurga, Logan Good, David Abood, Erin Nagle, Megan Duggan, Andrew Stiff, Mallory J. DiVincenzo, Lorena P. Suarez-Kelly, Amanda Campbell, Lianbo Yu, Robert Wesolowski, Harrison Howard, Hiral Shah, Kari Kendra, William E. Carson
Summary: In melanoma patients receiving immune checkpoint inhibitors, MDSC levels increased significantly in some responders, while PMN-MDSC decreased and CD14+CD15+ MDSC increased significantly in PD patients. Changes in MDSC levels may have prognostic value in immune checkpoint inhibitor therapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Ruyu Pi, Yang Yang, Xiaoyi Hu, Hongyi Li, Houhui Shi, Yu Liu, Xi Wang, An Tong, Tianqi Lu, Yuquan Wei, Xia Zhao, Xiawei Wei
Summary: High mTORC2 expression level in EOC is associated with poor prognosis, while AZD2014 inhibits tumor growth, reduces peritoneal ascites, and prolongs survival in tumor-bearing mice. In addition, AZD2014 also reduces MDSC accumulation and delays tumor recurrence in EOC models.
Review
Medicine, Research & Experimental
Shuchen Chen, He Duan, Gongping Sun
Summary: The evolving understanding of cellular metabolism has revealed the promise of targeting metabolism to modulate anticancer immunity. The combination of metabolic inhibitors with immune checkpoint blockade, chemotherapy, and radiotherapy may offer new approaches to cancer treatment. However, there is still a need for further exploration to optimize the use of these strategies despite the complex tumour microenvironment.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Immunology
Hossein Halimi, Shirin Farjadian
Summary: High concentrations of cholesterol and its metabolites impede immune responses against cancer cells, but lowering cholesterol levels can have positive effects in the treatment of certain malignancies by inhibiting tumor cell activities and promoting immune responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Vijay Kumar, John H. Stewart IV
Summary: Molecular carcinogenesis is a complex process involving abnormalities in key biological processes. The six hallmarks of cancer illustrate its complexity, including self-sufficient growth signals, apoptosis resistance, antigrowth signal resistance, neo-angiogenesis, invasion/spread, and limitless replicative potential. Chronic inflammation leads to immune cell metabolism dysregulation and cancer progression. This article highlights immunometabolic reprogramming as a critical hallmark of cancer and suggests targeting it for novel immunotherapeutic approaches.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Darren R. Heintzman, Emilie L. Fisher, Jeffrey C. Rathmell
Summary: T cell metabolism is dynamic and highly regulated, playing a crucial role in differentiation and function patterns; the ability of cells to acquire nutrients and cope with hostile environments can limit metabolic pathways; changes in physical conditions and nutrient availability shape immune responses.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Subir Biswas, Gunjan Mandal, Kyle K. Payne, Carmen M. Anadon, Chandler D. Gatenbee, Ricardo A. Chaurio, Tara Lee Costich, Carlos Moran, Carly M. Harro, Kristen E. Rigolizzo, Jessica A. Mine, Jimena Trillo-Tinoco, Naoko Sasamoto, Kathryn L. Terry, Douglas Marchion, Andrea Buras, Robert M. Wenham, Xiaoqing Yu, Mary K. Townsend, Shelley S. Tworoger, Paulo C. Rodriguez, Alexander R. Anderson, Jose R. Conejo-Garcia
Summary: Most ovarian cancers are infiltrated by activated T cells that have prognostic relevance, but they show low response rates to immune checkpoint inhibitors. On the contrary, memory B cell and plasma cell infiltrates associated with better outcomes may exert protective effects against tumor cells through B cell-derived IgA in ovarian cancer.
Article
Oncology
Manali S. Phadke, Zhihua Chen, Jiannong Li, Eslam Mohamed, Michael A. Davies, Inna Smalley, Derek R. Duckett, Vinayak Palve, Brian J. Czerniecki, Peter A. Forsyth, David Noyes, Dennis O. Adeegbe, Zeynep Eroglu, Kimberly T. Nguyen, Kenneth Y. Tsai, Uwe Rix, Christin E. Burd, Yian A. Chen, Paulo C. Rodriguez, Keiran S. M. Smalley
Summary: In mouse models of BRAF- and NRAS-mutant melanoma, upfront immunotherapy enhances responses to targeted therapy. The sequence of IT -> TT modulates the immune environment, increasing infiltration of T cells and decreasing tumor-associated macrophages, leading to improved therapeutic outcomes. Durable responses to the IT -> TT sequence depend on T-cell activity and enrichment of a population of melanoma cells with increased expression of MHC class I and melanoma antigens.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Cell Biology
Jessica K. Mandula, Paulo C. Rodriguez
Summary: MDSCs impair anti-tumor immunity in cancer by responding to various tumor-associated stressors, leading to immunosuppressive programming; therapeutic targeting of these stress axes could potentially overcome MDSC-related immune suppression in tumor bearing hosts. This review discusses the impact of tumor-associated stress on MDSC development, accumulation, and immunosuppressive function, as well as strategies aimed at overcoming this detrimental impact.
CELLULAR IMMUNOLOGY
(2021)
Article
Immunology
Alvaro de Mingo Pulido, Kay Hanggi, Daiana P. Celias, Alycia Gardner, Jie Li, Bruna Batista-Bittencourt, Eslam Mohamed, Jimena Trillo-Tinoco, Olabisi Osunmakinde, Reymi Pena, Alexis Onimus, Tsuneyasu Kaisho, Johanna Kaufmann, Kristen McEachern, Hatem Soliman, Vincent C. Luca, Paulo C. Rodriguez, Xiaoqing Yu, Brian Ruffell
Summary: Blockade of the inhibitory receptor TIM-3 has shown efficacy in clinical trials of cancer immunotherapy, specifically in enhancing antitumor immunity in mammary carcinomas by increasing CXCL9 expression by cDC1 cells. This increased expression required type I interferons and extracellular DNA, with DNA uptake and efficacy of TIM-3 blockade being dependent on HMGB1 and galectin-9-induced cell surface clustering of TIM-3, suggesting a potential mechanism for TIM-3 immunotherapy.
Article
Oncology
Gunjan Mandal, Subir Biswas, Carmen M. Anadon, Xiaoqing Yu, Chandler D. Gatenbee, Sandhya Prabhakaran, Kyle K. Payne, Ricardo A. Chaurio, Alexandra Martin, Patrick Innamarato, Carlos Moran, John J. Powers, Carly M. Harro, Jessica A. Mine, Kimberly B. Sprenger, Kristen E. Rigolizzo, Xuefeng Wang, Tyler J. Curiel, Paulo C. Rodriguez, Alexander R. Anderson, Ozlen Saglam, Jose R. Conejo-Garcia
Summary: This study reveals the crucial role of humoral immunity in human endometrial cancer and provides insights for the development of novel immunotherapies against this prevalent malignancy. Coordinated cellular and humoral immune responses, particularly involving B cells and IgA:plgR interactions, determine the progression of endometrial cancer and its response to treatment.
Article
Immunology
Ricardo A. Chaurio, Carmen M. Anadon, Tara Lee Costich, Kyle K. Payne, Subir Biswas, Carly M. Harro, Carlos Moran, Antonio C. Ortiz, Carla Cortina, Kristen E. Rigolizzo, Kimberly B. Sprenger, Jessica A. Mine, Patrick Innamarato, Gunjan Mandal, John J. Powers, Alexandra Martin, Zhitao Wang, Sumit Mehta, Bradford A. Perez, Roger Li, John Robinson, Jodi L. Kroeger, Tyler J. Curiel, Xiaoqing Yu, Paulo C. Rodriguez, Jose R. Conejo-Garcia
Summary: Regulation of PD-1 expression on Tfh cells affects Tfh cell differentiation. Inhibiting SATB1 expression promotes Tfh cell differentiation and enhances immune responses. Transfer of Tfh cells can induce TLS formation and inhibit tumor growth.
Article
Oncology
Amrita Basu, Gabriella K. Albert, Sabrina Awshah, Jashodeep Datta, Krithika N. Kodumudi, Corey Gallen, Amber Beyer, Keiran S. M. Smalley, Paulo C. Rodriguez, Derek R. Duckett, Peter A. Forsyth, Aixa Soyano, Gary K. Koski, Ricardo Lima Barros Costa, Heather Han, Hatem Soliman, Marie Catherine Lee, Pawel Kalinski, Brian J. Czerniecki
Summary: This study identifies immunogenic MHC class II-binding HER3 peptides that elicit HER3-specific CD4(+) Th1 responses, suggesting their potential application in immunotherapies for HER3-overexpressing tumors.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Biology
Alyssa Obermayer, Li Dong, Qianqian Hu, Michael Golden, Jerald D. D. Noble, Paulo Rodriguez, Timothy J. J. Robinson, Mingxiang Teng, Aik-Choon Tan, Timothy I. I. Shaw
Summary: This paper presents a R Shiny framework called DRPPM-EASY for integrative multi-omics analysis of cancer datasets. The framework provides a user-friendly interface for exploring and integrating various omics data, reducing the need for computational experience. By analyzing transcriptomic and proteomic data, the authors identified cancer cell proliferative features associated with USP7 gene knockout and disruption of protein degradation and spliceosome. Additionally, they developed an extension called DRPPM-EASY-CCLE with preloaded cancer cell line data for sample querying and phenotype assignment.
Editorial Material
Oncology
Jessica K. Mandula, Paulo C. Rodriguez
Summary: This study demonstrates how tumors can manipulate erythroid progenitors to promote immunosuppression. These reprogrammed cells, similar to myeloid-derived suppressor cells, are associated with poor response to immune-checkpoint inhibitors and tumor-related anemia.
Article
Oncology
Carmen M. Anadon, Xiaoqing Yu, Kay Hanggi, Subir Biswas, Ricardo A. Chaurio, Alexandra Martin, Kyle K. Payne, Gunjan Mandal, Patrick Innamarato, Carly M. Harro, Jessica A. Mine, Kimberly B. Sprenger, Carla Cortina, John J. Powers, Tara Lee Costich, Bradford A. Perez, Chandler D. Gatenbee, Sandhya Prabhakaran, Douglas Marchion, Mirjam H. M. Heemskerk, Tyler J. Curiel, Alexander R. Anderson, Robert M. Wenham, Paulo C. Rodriguez, Jose R. Conejo-Garcia
Summary: This study reveals that tissue-resident memory (TRM) cells are the main type of T cells infiltrating ovarian cancer. These TRM cells, specifically the progenitor TRMstem cells, play a crucial role in predicting the outcome of ovarian cancer. The findings suggest that ovarian cancer is immunogenic, but only a small portion of tumor-infiltrating T cells have tumor antigen reactivity.
Article
Oncology
Paramita Chakraborty, Rasesh Y. Parikh, Seungho Choi, Danh Tran, Monika Gooz, Zachariah T. Hedley, Do-Sung Kim, Dariusz Pytel, Inhong Kang, Satish N. Nadig, Gyda C. Beeson, Lauren Ball, Meenal Mehrotra, Hongjun Wang, Stefano Berto, Viswanathan Palanisamy, Hong Li, Shilpak Chatterjee, Paulo C. Rodriguez, Eduardo N. Maldonado, J. Alan Diehl, Vamsi K. Gangaraju, Shikhar Mehrotra
Article
Oncology
Jiannong Li, Inna Smalley, Zhihua Chen, Jheng-Yu Wu, Manali S. Phadke, Jamie K. Teer, Thanh Nguyen, Florian A. Karreth, John M. Koomen, Amod A. Sarnaik, Jonathan S. Zager, Nikhil I. Khushalani, Ahmad A. Tarhini, Vernon K. Sondak, Paulo C. Rodriguez, Jane L. Messina, Y. Ann Chen, Keiran S. M. Smalley
Summary: This study used single-cell RNA sequencing to analyze acral melanoma and found that it has a suppressed immune environment compared to non-acral cutaneous melanoma. Multiple therapeutically tractable immune checkpoints were observed in acral melanoma, offering new options for clinical translation.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Vincent Law, Zhihua Chen, Francesca Vena, Inna Smalley, Robert Macaulay, Brittany R. Evernden, Nam Tran, Yolanda Pina, John Puskas, Gisela Caceres, Simon Bayle, Joseph Johnson, James K. C. Liu, Arnold Etame, Michael Vogelbaum, Paulo Rodriguez, Derek Duckett, Brian Czerniecki, Ann Chen, Keiran S. M. Smalley, Peter A. Forsyth
Summary: This study demonstrates that CSF-CTCs can be grown in vitro and in vivo from some melanoma patients with LMD and used as preclinical models. These models retained melanoma expression patterns and had signaling pathways that are therapeutically targetable.
Article
Oncology
Xiaofei Song, Shiun Chang, Lucia Seminario-Vidal, Alvaro de Mingo Pulido, Leticia Tordesillas, Xingzhi Song, Rhianna A. Reed, Andrea Harkins, Shannen Whiddon, Jonathan Nguyen, Carlos Moran Segura, Chaomei Zhang, Sean Yoder, Zena Sayegh, Yun Zhao, Jane L. Messina, Carly M. Harro, Xiaohui Zhang, Jose R. Conejo-Garcia, Anders Berglund, Lubomir Sokol, Jianhua Zhang, Paulo C. Rodriguez, James J. Mule, Andrew P. Futreal, Kenneth Y. Tsai, Pei-Ling Chen
Summary: This study comprehensively investigated the tumor ecosystem of transformed CTCL using multiomics approaches. The findings revealed high tumor mutation burden, recurrently mutated pathways, and immune escape related changes in tCTCL. In addition, pharmacologic perturbation targeting OXPHOS and MYC showed promising antitumor activities, and intercellular communications between malignant T cells and macrophages/B cells were identified.
Article
Medicine, General & Internal
Maria Dulfary Sanchez-Pino, William S. Richardson, Jovanny Zabaleta, Ramesh Thylur Puttalingaiah, Andrew G. Chapple, Jiao Liu, Yonghyan Kim, Michelle Ponder, Randi DeArmitt, Lyndsey Buckner Baiamonte, Dorota Wyczechowska, Liqin Zheng, Amir A. Al-Khami, Jone Garai, Rachel Martini, Melissa Davis, Jessica Koller Gorham, James B. Wooldridge, Paulo C. Rodriguez, Lucio Miele, Augusto C. Ochoa
Summary: The number of LDN in the circulation is increased in obese patients and is associated with an inflammatory gene signature. Bariatric surgery significantly reduces LDN levels and improves metabolic parameters.
