Article
Immunology
Helena Nunes-Cabaco, Andreia Ramalho-dos-Santos, Ana R. Pires, Leila R. Martins, Joao T. Barata, Ana E. Sousa
Summary: IL-4 plays a role in the regulation of human thymocyte plasticity and is involved in the generation of CD8+ T cells in the thymus. IL-4 also has implications in neonatal immunity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Georgiana Toma, Ioana Maria Lemnian, Eliza Karapetian, Ivo Grosse, Barbara Seliger
Summary: Memory CD8(+) T cells increase with aging, leading to higher susceptibility to infections and decreased vaccine efficiency. In this study, the age-dependent expression profile of CD8(+) T cells from young and old donors was analyzed. The results showed that CD8(+)CD45RA(-) memory T cells from old donors maintained the characteristics of total CD8(+) T cells, including increased cytokine secretion and JAK-STAT pathway transcripts.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Eliza Mari Kwesi-Maliepaard, Heinz Jacobs, Fred van Leeuwen
Summary: T-AIM cells are a subset of memory T cells that develop memory features independently of antigen exposure. They exhibit characteristics similar to conventional memory cells, including antigen-specific responses and responsiveness to innate stimuli. T-AIM cells are suggested to provide additional levels of protection against infections and cancer.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Immunology
Yingyu Qin, Xueyang Bao, Mingzhu Zheng
Summary: CD8(+) T cells from the adaptive immune system and iNKT cells from the innate-like T lymphocytes both play important roles in defending against infections and cancers. CD8(+) T cell-based immunotherapy is a promising approach for the eradication of tumor cells, and iNKT cells contribute to CD8(+) T cell immunity through cross-priming and memory formation. This review also discusses recent advances in understanding the mechanisms of memory CD8(+) T cell differentiation and aging-induced impairment of T cell immunity.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Ahto Salumets, Liina Tserel, Anna P. Rumm, Lehte Turk, Kulli Kingo, Kai Saks, Astrid Oras, Raivo Uibo, Riin Tamm, Hedi Peterson, Kai Kisand, Part Peterson
Summary: Age-related changes in T-cell populations play an important role in immunosenescence. CD8(+) TEMRA cells and their subsets have characteristics of cellular senescence and increase in older individuals and age-related chronic inflammatory diseases. CD8(+) TEMRA proportions correlate with cytomegalovirus (CMV) antibody levels but not with chronological age. TRANCE/RANKL levels are associated with differentiated T-cell populations, including CD8(+) TEMRA and its CD28(-) subsets. Deep-amplicon bisulfite sequencing can be used to predict CD8(+) TEMRA cell proportions as a biomarker of immunosenescence.
Article
Cell Biology
Tucker J. Piergallini, Julia M. Scordo, Anna Allue-Guardia, Paula A. Pino, Hao Zhang, Hong Cai, Yufeng Wang, Larry S. Schlesinger, Jordi B. Torrelles, Joanne Turner
Summary: Inflammation plays a crucial role in lung infection, including tuberculosis caused by Mycobacterium tuberculosis. However, the specific impact of inflammation on regulating lymphocyte function is not well understood. To address this knowledge gap, the researchers used an acute lipopolysaccharide (LPS) treatment in young mice to study how inflammation affects CD8 T cell subsets. The findings show that acute inflammation can affect CD8 T cells, potentially impacting immune control in various disease states.
JOURNAL OF LEUKOCYTE BIOLOGY
(2023)
Article
Biology
Oksana Tsyklauri, Tereza Chadimova, Veronika Niederlova, Jirina Kovarova, Juraj Michalik, Iva Malatova, Sarka Janusova, Olha Ivashchenko, Helene Rossez, Ales Drobek, Hana Vecerova, Virginie Galati, Marek Kovar, Ondrej Stepanek
Summary: In this study, it was identified that Tregs limit the availability of IL-2, thereby suppressing the formation of a previously uncharacterized subset of antigen-stimulated KILR CD8(+) effector T cells. These KILR CD8(+) T cells exhibit superior cell-killing abilities and can be induced by the administration of agonistic IL-2 immunocomplexes. This research has potential implications for immunotherapy targeting these cells in humans.
Article
Immunology
Rui Dai, Xiaopei Huang, Yiping Yang
Summary: This study demonstrates the critical role of gamma delta T cells in promoting the CD8(+) T cell response to VV infection. Gamma delta T cells are able to present viral antigens and activate CD8(+) T cells, with MyD88 signaling playing a key role in this process. Understanding the regulation of adaptive T cell response by gamma delta T cells may provide insight for the development of more effective vaccine strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Vivek Verma, Nazli Jafarzadeh, Shannon Boi, Subhadip Kundu, Zhinuo Jiang, Yiping Fan, Jose Lopez, Rahul Nandre, Peng Zeng, Fatmah Alolaqi, Shamim Ahmad, Pankaj Gaur, Simon T. Barry, Viia E. Valge-Archer, Paul D. Smith, Jacques Banchereau, Mikayel Mkrtichyan, Benjamin Youngblood, Paulo C. Rodriguez, Seema Gupta, Samir N. Khleif
Summary: MEKi inhibition can induce CD8(+) T cell reprogramming into cells with stem cell-like memory characteristics, which exhibit stronger antitumor responses.
Review
Immunology
Toshiro Hirai, Yasuo Yoshioka
Summary: The primary goal of respiratory virus protection vaccines is to induce neutralizing antibodies for a long period. However, recent studies have shown that CD8(+) T cell-mediated immunity plays a crucial role in combating SARS-CoV-2 variants. Modern vaccine platforms such as mRNA and adenoviral vector vaccines can induce strong CD8(+) T cell-mediated immunity. Mucosal immunization may be necessary to establish a barrier of CD8(+) T cells for optimal protection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Weiwei Wang, Jing Zhao, Changlong Hao, Shudong Hu, Chen Chen, Yi Cao, Zhengyu Xu, Jun Guo, Liguang Xu, Maozhong Sun, Chuanlai Xu, Hua Kuang
Summary: This study discovers the potential of chiral nanomaterials as immunoadjuvants for the prevention and treatment of cancer. Chiral nanoparticles enhance immune response and inhibit tumor growth through the stimulation of specific cell types, showing better therapeutic effects compared to achiral nanoparticles.
ADVANCED MATERIALS
(2022)
Review
Immunology
Rosanne D. Reitsema, Annemieke M. H. Boots, Kornelis S. M. van der Geest, Maria Sandovici, Peter Heeringa, Elisabeth Brouwer
Summary: Vasculitis is a disease that causes inflammation of blood vessels and can lead to serious complications, with different forms such as Giant Cell Arteritis and Granulomatosis with Polyangiitis affecting different vessels and organs. CD8+ T cells play important roles in the immunopathogenesis of GCA and GPA, and aging may be associated with CD8+ T cell phenotype and function in these diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Daan K. J. Pieren, Noortje A. M. Smits, Rimke J. Postel, Vinitha Kandiah, Jelle de Wit, Josine van Beek, Debbie van Baarle, Teun Guichelaar
Summary: Aging leads to decreased immune responsiveness, known as immunosenescence. This study identifies novel markers associated with immunosenescence in CD8(+) T cells and shows that these features become prominent even in the earlier differentiation states of these cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Andreas Hombach, Markus Barden, Lisa Hannappel, Markus Chmielewski, Gunter Rappl, Agapios Sachinidis, Hinrich Abken
Summary: This study presents a new prototype of CARs that improves tumor recognition and elimination by incorporating the cytokine IL12 into the CAR exodomain. It reprograms CAR T cells to have NK cell-like functional capacities, allowing them to target and eliminate antigen-negative cancer cells.
Article
Immunology
Hong-Yi Zheng, Xue-Hui Wang, Xiao-Yan He, Min Chen, Ming-Xu Zhang, Xiao-Dong Lian, Jia-Hao Song, Yan Hu, Wei Pang, Yun Wang, Zheng-Fei Hu, Long-Bao Lv, Yong-Tang Zheng
Summary: The number of elderly people living with HIV is increasing globally. The impact of HIV infection combined with aging on the immune homeostasis of secondary lymphoid organs remains unclear. This study found that SIV production and CD4/CD8 ratio inversion were more severe in old Chinese rhesus macaques compared to young ones, especially with infiltrated CD8+ T cells in the follicles and germinal centers. The highly activated STAT3 in these follicular CXCR5+CD8+ T cells might be caused by the severe inflammatory milieu in the follicles of old macaques, indicating that aging may contribute to SIV-induced immune disorders in secondary lymphoid tissues.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Immunology
Constanza Savid-Frontera, Maria E. Viano, Natalia S. Baez, Della Reynolds, Mariana Matellon, Howard A. Young, Maria C. Rodriguez-Galan
Summary: This study demonstrates that utilizing IL-12 cDNA can safely treat tumors and control tumor growth in mouse models. Systemic IL-12 expression leads to a higher frequency of tumor-infiltrated cells and IFN-γ-producing CD8(+) T cells, along with a lower frequency of regulatory CD4(+)FOXP3(+) and CD11b(+)Gr-1(+) cells.
Article
Multidisciplinary Sciences
Alex Cordero, Matthew D. Ramsey, Deepak Kanojia, Jawad Fares, Edgar Petrosyan, Charles W. Schwartz, Rachel Burga, Peng Zhang, Aida Rashidi, Brandyn Castro, Ting Xiao, Catalina Lee-Chang, Jason Miska, Irina Balyasnikova, Atique U. Ahmed, Maciej S. Lesniak
Summary: This study engineered neural stem cells to secrete antibodies against HER2, inhibiting the progression of breast cancer brain metastases. The combination therapy with the tyrosine kinase inhibitor tucatinib showed promising results in animal models.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Editorial Material
Oncology
Catalina Lee-Chang
Correction
Cell Biology
Jason Miska, Catalina Lee-Chang, Aida Rashidi, Megan E. Muroski, Alan L. Chang, Aurora Lopez-Rosas, Peng Zhang, Wojciech K. Panek, Alex Cordero, Yu Han, Atique U. Ahmed, Navdeep S. Chandel, Maciej S. Lesniak
Review
Oncology
Toni Q. Cao, Derek A. Wainwright, Catalina Lee-Chang, Jason Miska, Adam M. Sonabend, Amy B. Heimberger, Rimas Lukas
Summary: Despite current standard treatments, prognosis for glioblastoma patients remains poor. Immunotherapy, which harnesses the patient's immune system, has shown success in non-central nervous system cancers but lacks efficacy for glioblastoma. Factors impacting immunotherapy efficacy for glioblastoma have become a new focus of research.
Article
Oncology
Kanako Moritoh, Koichiro Shoji, Yosuke Amagai, Tomoko Fujiyuki, Hiroki Sato, Misako Yoneda, Chieko Kai
Summary: We established an immunocompetent mouse cancer model by introducing the NECTIN4 gene into mouse cancer cells, which allowed us to study the immune response after rMV-SLAMblind therapy. Our findings show that rMV-SLAMblind significantly suppressed tumor growth and activated natural killer cells, type 1 helper T cells, and tumor-specific CD8(+) T cells in the tumor microenvironment. CD8(+) cells played a significant role in the therapeutic efficacy of rMV-SLAMblind.
Review
Oncology
Edgar Petrosyan, Jawad Fares, Luis G. Fernandez, Ragini Yeeravalli, Crismita Dmello, Joseph T. Duffy, Peng Zhang, Catalina Lee-Chang, Jason Miska, Atique U. Ahmed, Adam M. Sonabend, Irina Balyasnikova, Amy B. Heimberger, Maciej S. Lesniak
Summary: Immunotherapy has had success in halting cancer progression, but it has not been effective for primary brain malignancies, which remain a globally lethal disease. Understanding how tumor cells survive and propagate within the unique microenvironment of the central nervous system (CNS) is crucial. Cancer genetic aberrations and metabolic abnormalities lead to persistent endoplasmic reticulum (ER) stress, which promotes tumor growth, invasion, therapeutic resistance, and reprogramming of immune cells. Targeting ER stress is a potential therapeutic approach for primary CNS tumors.
MOLECULAR CANCER RESEARCH
(2023)
Article
Multidisciplinary Sciences
Crismita Dmello, Junfei Zhao, Li Chen, Andrew Gould, Brandyn Castro, Victor A. Arrieta, Daniel Y. Zhang, Kwang-Soo Kim, Deepak Kanojia, Peng Zhang, Jason Miska, Ragini Yeeravalli, Karl Habashy, Ruth Saganty, Seong Jae Kang, Jawad Fares, Connor Liu, Gavin Dunn, Elizabeth Bartom, Matthew J. Schipma, Patrick D. Hsu, Mahmoud S. Alghamri, Maciej S. Lesniak, Amy B. Heimberger, Raul Rabadan, Catalina Lee-Chang, Adam M. Sonabend
Summary: This study identifies Chek2 as the most important kinase that promotes evasion of glioma cells from immune recognition. Genetic depletion or pharmacological inhibition of Chek2 enhances antigen presentation, STING pathway activation, and PD-L1 expression, leading to survival benefits in preclinical glioma models. Analysis of human GBMs shows a negative correlation between Chek2 expression and antigen presentation/T-cell activation. These results suggest that Chek2 may be a promising target for improving response to immune checkpoint blockade therapy.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Peng Zhang, Aida Rashidi, Junfei Zhao, Caylee Silvers, Hanxiang Wang, Brandyn Castro, Abby Ellingwood, Yu Han, Aurora Lopez-Rosas, Markella Zannikou, Crismita Dmello, Rebecca Levine, Ting Xiao, Alex Cordero, Adam M. Sonabend, Irina V. Balyasnikova, Catalina Lee-Chang, Jason Miska, Maciej S. Lesniak
Summary: The study describes the use of a bridging-lipid nanoparticle (B-LNP) that engages tumor-associated myeloid cells (TAMCs) to glioblastoma cells via anti-CD47/PD-L1 dual ligation. The B-LNPs block CD47 and PD-L1, promote TAMC phagocytic activity, and enhance T cell recruitment and antitumor responses. The administration of B-LNP/diABZI combined with radiotherapy promotes brain tumor regression and induces immunological memory against glioma.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Markella Zannikou, Joseph T. Duffy, Rebecca N. Levine, Maggie Seblani, Qianli Liu, Aaron Presser, Victor A. Arrieta, Christopher J. Chen, Adam M. Sonabend, Craig M. Horbinski, Catalina Lee-Chang, Jason Miska, Maciej S. Lesniak, Stephen Gottschalk, Irina Balyasnikova
Summary: This study found that IL15 can potentially be used to directly target myeloid-derived suppressor cells (MDSCs) in the immunosuppressive tumor microenvironment (TME) of glioblastoma (GBM). IL15-modified CAR-T cells efficiently depleted MDSCs and significantly improved survival in GBM mouse models. The results suggest that IL15-modified CAR-T cells have dual targeting effects against tumor cells and MDSCs in GBM, warranting further evaluation in early-phase clinical studies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Biochemical Research Methods
David Hou, Joshua L. Katz, Catalina Lee-Chang
Summary: In this article, a B-cell-based cellular vaccine (BVax) is introduced, which is able to select tumor-specific B cells and generate tumor-specific antibodies and activate T cells in ex vivo culture. The protocol for generating a B-cell-based vaccine in a CT2A orthotopic glioma murine model is described, including glioma cell implantation, tissue harvesting, 4-1BBL+ B cell isolation, and activation. The article also provides methods for assessing BVax phenotype in vitro and in vivo functional status.
Article
Nutrition & Dietetics
Heekyong R. Bae, Su-Kyung Shin, Youngji Han, Ji-Hyeon Yoo, Suntae Kim, Howard A. Young, Eun-Young Kwon
Summary: The rare sugar D-allulose has potential benefits in addressing metabolic disorders such as obesity and type 2 diabetes (T2D) by improving insulin resistance through mitigating disruptions in macrophage and mitochondrial function.
Article
Medicine, Research & Experimental
Victor A. Arrieta, Crismita Dmello, Daniel J. McGrail, Daniel J. Brat, Catalina Lee-Chang, Amy B. Heimberger, Dhan Chand, Roger Stupp, Adam M. Sonabend
Summary: Immune checkpoint blockade (ICB) has revolutionized modern cancer therapy, arousing great interest in the neuro-oncology community. While several reports show that subsets of patients with glioma exhibit durable responses to immunotherapy, the efficacy of this treatment has not been observed for unselected patient populations, preventing its broad clinical implementation for gliomas and glioblastoma (GBM).
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Review
Medicine, Research & Experimental
Catalina Lee-Chang, Maciej S. Lesniak
Summary: Antigen presentation machinery and professional antigen-presenting cells (APCs) are crucial for an effective immune response against cancers, particularly in T cell-centric immunotherapy. Dendritic cells (DCs), the gold standard APCs, are essential in initiating and maintaining specific adaptive immunity. The use of ex vivo-differentiated DCs from circulating CD14+ monocytes loaded with tumor-associated antigens, synthetic peptides, or RNA in activating antitumor T cells has paved the way for alternative antigen-presenting vaccination strategies. This review discusses the past, present, and future of APC immune therapeutics in the context of primary brain tumors.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Immunology
Tihong Shao, Patrick S. C. Leung, Weici Zhang, Koichi Tsuneyama, William M. Ridgway, Howard A. Young, Zongwen Shuai, Aftab A. Ansari, M. Eric Gershwin
Summary: By inhibiting the JAK/STAT signaling pathway, the development and progression of autoimmune cholangitis can be effectively blocked. This study found that ruxolitinib treatment can reduce inflammation, lower autoantibody levels, and alter macrophage polarization, which holds important immunological and clinical significance for cholangitis.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
