Review
Immunology
Meihong Da, Luxia Chen, Alexander Enk, Sabine Ring, Karsten Mahnke
Summary: Adenosine (Ado) has immunosuppressive effects, and the ectoenzyme CD73 is crucial for the production of extracellular Ado. CD73 is highly expressed in regulatory T cells (Tregs) and upregulated after activation. Ado generated by CD73(+) Tregs plays a role in immune suppression of dendritic cells, monocytes, and T cells, making CD73 a novel checkpoint inhibitor in immunosuppressive environments such as tumors. Therapeutic intervention targeting CD73 is currently under investigation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Giuseppe Bronte, Alberto Verlicchi, Serena De Matteis, Alice Rossi, Alessandra Affatato, Francesco Giulio Sullo, Caterina Gianni, Matteo Canale, Marco Angelo Burgio, Angelo Delmonte, Michele Milella, Lucio Crino
Summary: Immune checkpoint inhibition has shown significant progress in treating non-small cell lung cancer patients, though resistance mechanisms like myeloid-derived suppressor cells and exhausted immune cells may limit effectiveness. Analyzing changes in immune cell subsets and disease progression during treatment could offer insights for developing new targets or biomarkers for cancer immunotherapy resistance.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Claudia Giannotta, Federica Autino, Massimo Massaia
Summary: Myeloid derived suppressor cells (MDSC) have significant roles in regulating immune homeostasis and immune responses, especially in cancer. MDSC interact with cancer cells in the tumor microenvironment through various mechanisms such as producing soluble factors, expressing inhibitory molecules, rewiring metabolism, and releasing exosomes. The relationship between MDSC and tumor cells leads to immune evasion and cancer growth. In multiple myeloma (MM), MDSC play a major role in creating a tumor-promoting microenvironment. This minireview discusses the interplay between MDSC and MM microenvironment, as well as potential strategies to target MDSC.
FRONTIERS IN IMMUNOLOGY
(2023)
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
Oncology
Adam N. R. Cartwright, Shengbao Suo, Soumya Badrinath, Sushil Kumar, Johannes Melms, Adrienne Luoma, Archis Bagati, Assieh Saadatpour, Benjamin Izar, Guo-Cheng Yuan, Kai W. Wucherpfennig
Summary: The study demonstrates that MDSCs do not block early steps of T-cell activation but induce DNA damage and p53 pathway activation in CD8(+) T cells through an iNOS-dependent pathway.
CANCER IMMUNOLOGY RESEARCH
(2021)
Review
Oncology
Maximilian Haist, Henner Stege, Stephan Grabbe, Matthias Bros
Summary: Immunotherapy has shown benefits for advanced cancer patients, but many still do not respond to treatment. The accumulation of immunosuppressive cell populations like MDSC and Treg in the tumor microenvironment contributes to immune resistance and limits the effectiveness of immunotherapy.
Article
Biochemistry & Molecular Biology
Jordan K. Vance, Travis W. Rawson, Jessica M. Povroznik, Kathleen M. Brundage, Cory M. Robinson
Summary: Neonates have an increased risk of infectious diseases, partly due to the abundance and dynamic activity of myeloid-derived suppressor cells (MDSCs) during an infection. These MDSCs modulate gene expression and exhibit variable effector responses to pathogen-associated molecular patterns (PAMPS) on bacteria like E. coli, ultimately leading to enhanced immune suppression and inhibition of protective immunity in early life.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Jane Alexandra Shaw, Stephanus T. Malherbe, Gerhard Walzl, Nelita du Plessis
Summary: Epidemiologic data indicate that both current and previous tuberculosis (TB) increase the risk of in-hospital mortality from COVID-19, and a similar trend is observed for poor outcomes from Mtb infection after recent SARS-CoV-2. Dysregulation of immunity explains the dual risk posed by co-infection, with a dysfunctional innate immune response observed in COVID-19. Myeloid-derived suppressor cells (MDSC) play a crucial role in this process by becoming immunosuppressive and impairing pathogen clearance. MDSC are enriched in severe COVID-19 patients and are associated with higher levels of inflammatory cytokines.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Xiaoqing Chen, Xue Liu, Yichao Jiang, Ningshao Xia, Chao Liu, Wenxin Luo
Summary: Chronic hepatitis B virus (HBV) infection is a major public health challenge, with over 250 million people worldwide infected. Priming of naive HBV-specific CD8 T cells is hindered, and this is closely related to abnormalities in the complex immune microenvironment. In this article, we summarize recent progress in understanding the abnormal priming of HBV-specific CD8 T cells and discuss corresponding immunotherapies to facilitate their functional recovery. We also highlight the importance of balancing viral clearance and pathological liver injury induced by CD8 T-cell activation during drug development.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Laura J. Pallett, Leo Swadling, Mariana Diniz, Alexander A. A. Maini, Marius Schwabenland, Adria Dalmau Gasull, Jessica Davies, Stephanie Kucykowicz, Jessica K. K. Skelton, Niclas Thomas, Nathalie M. M. Schmidt, Oliver E. E. Amin, Upkar S. S. Gill, Kerstin A. A. Stegmann, Alice R. R. Burton, Emily Stephenson, Gary Reynolds, Matt Whelan, Jenifer Sanchez, Roel de Maeyer, Clare Thakker, Kornelija Suveizdyte, Imran Uddin, Ana M. M. Ortega-Prieto, Charlotte Grant, Farid Froghi, Giuseppe Fusai, Sabela Lens, Sofia Perez-del-Pulgar, Walid Al-Akkad, Giuseppe Mazza, Mahdad Noursadeghi, Arne Akbar, Patrick T. F. Kennedy, Brian R. R. Davidson, Marco Prinz, Benjamin M. M. Chain, Muzlifah Haniffa, Derek W. W. Gilroy, Marcus Dorner, Bertram Bengsch, Anna Schurich, Mala K. K. Maini
Summary: CD14(+)CD8(+) T cells in the liver exhibit immunomodulatory features and play a role in liver transplantation, infection, and tumors. These cells have high levels of IL-10 and IL-2 production, as well as enhanced antiviral/anti-tumor effector function. Additionally, these cells can enhance the tumor-killing ability of CD8(+) T cells by acquiring the lipopolysaccharide receptor complex from mononuclear phagocytes. Bacterial products and tissue stromal factors can tune liver immunity by driving myeloid instruction of CD8(+) T cells.
Article
Immunology
Juliette Ferrant, Faustine Lhomme, Simon Le Gallou, Jonathan M. Irish, Mikael Roussel
Summary: The study reviews the phenotypic and functional description of the circulating monocytic lineage in B cell lymphomas, providing initial insights into the heterogeneity of these cell populations and highlighting the potential of circulating myeloid regulatory cells as diagnostic and prognostic biomarkers in B-cell lymphomas.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Feng Shan, Anthony R. Cillo, Carly Cardello, Daniel Y. Yuan, Sheryl R. Kunning, Jian Cui, Caleb Lampenfeld, Asia M. Williams, Alexandra P. Mcdonough, Arjun Pennathur, James D. Luketich, John M. Kirkwood, Robert L. Ferris, Tullia C. Bruno, Creg J. Workman, Panayiotis V. Benos, Dario A. A. Vignali
Summary: Research identified an activated Tregs subpopulation expressing multiple tumor necrosis factor receptor genes in head and neck squamous cell carcinoma tumors, associated with worse prognosis. The transcription factor BATF plays a central role in limiting excessive activation and promoting the survival of activated T-regs. Additionally, a suite of surface molecules reflective of the BATF-driven transcriptional network on intratumoral T-regs was identified.
SCIENCE IMMUNOLOGY
(2021)
Article
Oncology
Can Altunbulakli, David G. Jimenez, David Askmyr, Aastha Sobti, Sabine Swoboda, Lennart Greiff, Malin Lindstedt
Summary: In this study, the inter-patient and intra-tumoral sources of variation in tonsillar cancer were explored using immunofluorescence and targeted spatial proteomics. The abundance of intra-tumoral CD8(+) T-cells was found to be a positive predictive marker for tonsillar cancer, and the expression of PD-L1 by these T-cells was associated with lower mortality. Differences in CD8(+) and CD11c(+) cells inside and outside the tumor suggest an immune cell-altering effect on the tumor microenvironment.
FRONTIERS IN ONCOLOGY
(2023)
Review
Immunology
Yudan Cui, Jingshan Cai, Wenxin Wang, Shengjun Wang
Summary: HDACIs are antitumor drugs that enhance gene transcription via epigenetic regulation, with cytotoxic properties against tumor cells. The effects of HDACIs on immunocytes in the tumor microenvironment, specifically MDSCs, are still not fully understood.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Medicine, Research & Experimental
Anik Pramanik, Sankar Bhattacharyya
Summary: The MDSC population in the tumor microenvironment plays a crucial role in tumor immune evasion and cancer progression by disrupting antitumor T cell activity and potentially affecting other immune cell functions.