Article
Cell Biology
Melissa G. Lechner, Zikang Zhou, Aline T. Hoang, Nicole Huang, Jessica Ortega, Lauren N. Scott, Ho -Chung Chen, Anushi Y. Patel, Rana Yakhshi-Tafti, Kristy Kim, Willy Hugo, Pouyan Famini, Alexandra Drakaki, Antoni Ribas, Trevor E. Angell, Maureen A. Su
Summary: Autoimmune toxicity is an increasing challenge in using immune checkpoint inhibitors for cancer treatment. This study investigated the immune infiltrates in ICI-thyroiditis patients and identified a dominant population of cytotoxic CD8+ T cells. The researchers also found that interleukin-21 played a crucial role in the formation of these thyrotoxic CD8+ T cells and validated the findings in a mouse model. These findings provide insights into the mechanisms and potential therapeutic targets for individuals with IRAEs.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Ryma Toumi, Yevgeniy Yuzefpolskiy, Adithya Vegaraju, Hanxi Xiao, Kendall A. Smith, Surojit Sarkar, Vandana Kalia
Summary: This study demonstrates that paracrine IL-2 is crucial for optimal primary expansion, effector and memory differentiation, and metabolic function in CD8 T cells, while autocrine IL-2 is uniquely required during primary expansion to program robust secondary expansion potential in memory-fated cells. Additionally, IL-2 production by antigen-specific CD8 T cells is largely independent of CD4 licensing of dendritic cells in inflammatory infections with robust DC activation.
Article
Immunology
Farhad Sabbaghi, Lorenz Ullner, Toszka Bohn, Jennifer Hahlbrock, Tobias Bopp, Edgar Schmitt, Matthias Klein, Michael Stassen
Summary: IL-9 is involved in various immune responses and is produced by different cell types. The study shows that NFATc2 has contradictory effects on IL-9 expression in different cell types and presents evidence of the critical role of autocrine IL-3 in BMMC for IL-9 production.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Oncology
Ryo Koyama-Nasu, Motoko Y. Kimura, Masahiro Kiuchi, Ami Aoki, Yangsong Wang, Yukiyoshi Mita, Ichita Hasegawa, Yukihiro Endo, Atsushi Onodera, Kiyoshi Hirahara, Shinichiro Motohashi, Toshinori Nakayama
Summary: This study reveals that CD69 regulates the differentiation process of tumor-specific CD8+ T cells through controlling the expression of transcription factor TOX. Lack of CD69 promotes the generation of functional terminally differentiated CD8+ T cells. Combined use of anti-CD69 and anti-PD-1 shows efficient antitumor effect.
CANCER IMMUNOLOGY RESEARCH
(2023)
Article
Immunology
Yuying Liu, Nannan Zhou, Li Zhou, Jing Wang, Yabo Zhou, Tianzhen Zhang, Yi Fang, Jinwei Deng, Yunfeng Gao, Xiaoyu Liang, Jiadi Lv, Zhenfeng Wang, Jing Xie, Yuanbo Xue, Huafeng Zhang, Jingwei Ma, Ke Tang, Yiliang Fang, Feiran Cheng, Chengjuan Zhang, Bing Dong, Yuzhou Zhao, Peng Yuan, Quanli Gao, Haizeng Zhang, F. Xiao-Feng Qin, Bo Huang
Summary: IL-2 acts as an environmental cue to induce CD8(+) T cell exhaustion within tumor microenvironments by activating STAT5, inducing tryptophan hydroxylase 1, and subsequently causing T cell dysfunction.
Article
Multidisciplinary Sciences
Andrea Papait, Elsa Vertua, Patrizia Bonassi Signoroni, Anna Cargnoni, Marta Magatti, Francesca Romana Stefani, Jacopo Romoli, Antonietta Rosa Silini, Ornella Parolini
Summary: We found that hAMSCs from human term placenta can affect the development and fate of CD8 T cells through multiple mechanisms, providing new insights into the treatment of diseases characterized by altered activation of memory subsets.
Article
Multidisciplinary Sciences
Seon-Hee Kim, Eunjung Cho, Yu Kim, Chungyong Han, Beom K. Choi, Byoung S. Kwon
Summary: The study demonstrates that post-conditioning treatment with anti-CD4 can enhance the anti-tumor efficacy of adoptive T cell therapy (ACT) by promoting the expansion of IL-18R alpha(hi) CD8(+) T cells. This combination treatment accelerates proliferation and differentiation of tumor-reactive CD8(+) T cells and improves tumor suppression and host survival. The enrichment of polyfunctional IL-18R alpha(hi) CD8(+) T cells plays a key role in the induced tumor suppression, mediated by IL-18 signaling and TCR-MHC I interaction.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Shannon M. Kahan, Rakesh K. Bakshi, Jennifer T. Ingram, R. Curtis Hendrickson, Elliot J. Lefkowitz, David K. Crossman, Laurie E. Harrington, Casey T. Weaver, Allan J. Zajac
Summary: The ability to produce IL-2 identifies constituents of the expanded CD8 T cell effector pool with stem-like features, which exhibit superior protective powers. The production of IL-2 by cells attenuates the ability to receive IL-2 signals, limiting terminal effector formation and conferring superior protection. Non-producing effector cells, on the other hand, gain effector traits at the expense of memory formation. Despite distinct properties during the effector phase, IL-2-producing and non-producing CD8 T cells converge transcriptionally as memory matures, forming populations with equal recall abilities.
SCIENCE IMMUNOLOGY
(2022)
Article
Oncology
Yi Fang, Min Chen, Guangfei Li, Yue Yang, Peijie He, Jian Chen, Lei Cheng, Haitao Wu
Summary: The characteristics of fibroblast cells in head and neck precancerous lesion and their ability to secrete inflammatory cytokines and affect CD8(+)T cell functions were investigated. Fibroblasts in vocal fold leukoplakia and cancer-associated fibroblasts in head and neck squamous cell carcinoma displayed similar cellular functions and robust inflammatory cytokine secretions. Fibroblasts from vocal fold leukoplakia induced apoptosis, depletion of CD8(+) T cells, and recruitment of regulatory T cells. An autocrine loop involving IL-6, TGF-beta, and the IL-6/JAK2/STAT3 pathway was observed in vocal fold leukoplakia fibroblasts. Inhibition of this pathway with a monoclonal antibody targeting IL-6R showed promising results in suppressing the progression of oral leukoplakia in vitro and in vivo.
Article
Cell Biology
Mahrukh A. Huseni, Lifen Wang, Joanna E. Klementowicz, Kobe Yuen, Beatrice Breart, Christine Orr, Li-fen Liu, Yijin Li, Vinita Gupta, Congfen Li, Deepali Rishipathak, Jing Peng, Yasin Senbabaoglu, Zora Modrusan, Shilpa Keerthivasan, Shravan Madireddi, Ying-Jiun Chen, Eleanor J. Fraser, Ning Leng, Habib Hamidi, Hartmut Koeppen, James Ziai, Kenji Hashimoto, Marcella Fasso, Patrick Williams, David F. McDermott, Jonathan E. Rosenberg, Thomas Powles, Leisha A. Emens, Priti S. Hegde, Ira Mellman, Shannon J. Turley, Mark S. Wilson, Sanjeev Mariathasan, Luciana Molinero, Mark Merchant, Nathaniel R. West
Summary: IL-6 is identified as a correlate of poor response to atezolizumab in clinical trials of advanced kidney, breast, and bladder cancers. In pre-clinical models, combined blockade of PD-L1 and IL-6 receptor (IL6R) has synergistic regression effects on tumors and improves anti-tumor CD8+ cytotoxic T lymphocyte (CTL) responses. Agents targeting IL-6 signaling could be potential partners for combination with immune checkpoint inhibitors (ICIs) in cancer patients.
CELL REPORTS MEDICINE
(2023)
Article
Immunology
D. Alejandro Canaria, J. Alejandra Rodriguez, Luopin Wang, Franklin J. Yeo, Bingyu Yan, Mengbo Wang, Charlotte Campbell, Majid Kazemian, Matthew R. Olson
Summary: Tox is expressed in various T cell subtypes and promotes the differentiation of Th2 and Treg cells. Its overexpression induces the expression of genes involved in cell activation, cellular trafficking, and inflammation suppression. Tox regulates the transcription of these genes along with BATF, IRF4, and JunB.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Miao Ding, Yi Fei, Jianmin Zhu, Ji Ma, Guoqing Zhu, Ni Zhen, Jiabei Zhu, Siwei Mao, Fenyong Sun, Feng Wang, Qiuhui Pan
Summary: IL-27 directly improves the survival and cytotoxicity of adoptive T cells, promotes memory T cell differentiation in CD8(+) T cells, and enhances adoptive T cells' cancer immunity when delivered via tumor antigen-specific T cells.
Article
Immunology
Justus Ninnemann, Caroline Winsauer, Marina Bondareva, Anja A. Kuehl, Laura Lozza, Pawel Durek, Donata Lissner, Britta Siegmund, Stefan H. E. Kaufmann, Mir-Farzin Mashreghi, Sergei A. Nedospasov, Andrey A. Kruglov
Summary: Successful treatment of chronic inflammatory diseases requires both the cessation of inflammation and the promotion of tissue repair. Targeting tumor necrosis factor (TNF) can induce tissue repair in inflammatory bowel disease (IBD) patients, but the underlying molecular mechanisms have been unclear. Using an experimental colitis model, this study found that TNF interferes with tissue repair by inducing a soluble antagonist of IL-22. Furthermore, membrane-bound TNF expressed by T cells perpetuates colonic inflammation, while soluble TNF produced by epithelial cells inhibits colonic epithelial repair.
MUCOSAL IMMUNOLOGY
(2022)
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
Multidisciplinary Sciences
Fei Mo, Zhiya Yu, Peng Li, Jangsuk Oh, Rosanne Spolski, Liang Zhao, Caleb R. Glassman, Tori N. Yamamoto, Yun Chen, Filip M. Golebiowski, Dalton Hermans, Sonia Majri-Morrison, Lora K. Picton, Wei Liao, Min Ren, Xiaoxuan Zhuang, Suman Mitra, Jian-Xin Lin, Luca Gattinoni, Jonathan D. Powell, Nicholas P. Restifo, K. Christopher Garcia, Warren J. Leonard
Summary: Adoptive transfer of antigen-specific T cells is a significant advancement in cancer immunotherapy, and maintaining a stem-cell-like state before transfer is beneficial for therapeutic efficacy.