Article
Immunology
Valerie Janelle, Mathieu Neault, Marie-Eve Lebel, Dave Maurice De Sousa, Salix Boulet, Ludovic Durrieu, Cedric Carli, Chloe Muzac, Sebastien Lemieux, Nathalie Labrecque, Heather J. J. Melichar, Frederick A. Mallette, Jean-Sebastien Delisle
Summary: The development of T-cell dysfunction upon repeated antigen exposure involves the accumulation of DNA damage and activation of the p38MAPK signaling pathway, leading to cellular senescence features including p16(INK4a) upregulation. However, targeting p16(INK4a) can improve T-cell functionality in exhausted CAR T cells, suggesting T-cell senescence as a potential target in immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Kenji Shimizu, Daisuke Sugiura, Il-mi Okazaki, Takumi Maruhashi, Tatsuya Takemoto, Taku Okazaki
Summary: PD-1 preferentially inhibits the expression of TCR-inducible genes when TCR:pMHC affinity is low, demonstrating a qualitative control of T cell responses by suppressing low-affinity T cells. Peptide-MHC affinities and MHC expression levels do not affect PD-1 sensitivity, suggesting that the strength of individual TCR signal is the key determinant of PD-1 sensitivity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Physical
Tianyuan Xue, Zhirang Zhang, Tianliang Fang, Baoqi Li, Yuan Li, Liyan Li, Yanghua Jiang, Fangfang Duan, Fanqiang Meng, Xin Liang, Xudong Zhang
Summary: In this study, cellular vesicles displaying anti-PD-1 single-chain variable fragment antibody and A(2a) adenosine receptor antagonist CPI-444 were prepared to reinvigorate T cell immunity and enhance anti-tumor activation.
Article
Multidisciplinary Sciences
Maite Duhalde Vega, Daniela Olivera, Gustavo Gastao Davanzo, Mauricio Bertullo, Veronica Noya, Gabriela Fabiano de Souza, Stefanie Primon Muraro, Icaro Castro, Ana Paula Arevalo, Martina Crispo, German Galliussi, Sofia Russo, David Charbonnier, Florencia Rammauro, Mathias Jeldres, Catalina Alamon, Valentina Varela, Carlos Batthyany, Mariela Bollati-Fogolin, Pablo Oppezzo, Otto Pritsch, Jose Luiz Proenca-Modena, Helder I. Nakaya, Emiliano Trias, Luis Barbeito, Ignacio Anegon, Maria Cristina Cuturi, Pedro Moraes-Vieira, Mercedes Segovia, Marcelo Hill
Summary: This study reveals the correlation between inflammation and dysfunctional T cell responses, showing that manipulating T cells can control certain viral infections. These findings provide new insights for supporting immunotherapy targeting critical viral diseases.
Article
Oncology
Jiang Liu, Degan Liu, Guangyin Hu, Jingjing Wang, Dadong Chen, Chuanjun Song, Yin Cai, Chentong Zhai, Wenjing Xu
Summary: This study investigated the predictive values of circulating CD8(+) T cells and CD8(+)T/CD4(+)T cell ratio in advanced gastric cancer patients receiving immunotherapy. The results showed that patients with higher percentages of CD8(+) T and CD8(+) Tm expressing PD-1, as well as a higher PD-1(+)CD8(+)T/PD-1(+)CD4(+)T cell ratio, had better survival outcomes. These findings provide preliminary evidence for screening the population that would benefit from immunotherapy.
CANCER CELL INTERNATIONAL
(2023)
Article
Biochemistry & Molecular Biology
Christiane Majer, Holger Lingel, Aditya Arra, Hans-Gert Heuft, Dirk Bretschneider, Silke Balk, Katrin Vogel, Monika C. Brunner-Weinzierl
Summary: Newborn CD4 T-cells show activation-induced events and produce Th1 cytokines in response to Staphylococcus aureus, indicating their ability to mount immediate and controlled antibacterial responses. The proliferation of neonatal T-helper cells is influenced by sex, IL-2 receptor expression, and the PD-1/PD-L1 axis. In addition, the regulation of multifunctional T-helper cells is exclusively mediated by the PD-1/PD-L1 axis in neonatal CD4 T-cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Lissete Sanchez-Magraner, Juan Gumuzio, James Miles, Nicole Quimi, Purificacion Martinez del Prado, Maria Teresa Abad-Villar, Fernando Pikabea, Laura Ortega, Carmen Etxezarraga, Salvador Martin-Algarra, Maria D. Lozano, Monica Saiz-Camin, Mikel Egurrola-Izquierdo, Inmaculada Barredo-Santamaria, Alberto Saiz-Lopez, Jenifer Gomez-Mediavilla, Nerea Segues-Merino, Maria Aranzazu Juaristi-Abaunz, Ander Urruticoechea, Erica J. Geraedts, Kim van Elst, Niels J. M. Claessens, Antoine Italiano, Christopher J. Applebee, Sandra del Castillo, Charles Evans, Fernando Aguirre, Peter J. Parker, Veronique Calleja
Summary: Immunomodulatory ligand-receptor interactions play a crucial role in cancer immunoevasion. A study on non-small cell lung carcinoma patients revealed the heterogeneity of PD-1/PD-L1 immune checkpoint engagement and its correlation with treatment response. The functional readout of PD-1/PD-L1 interaction can significantly improve patient stratification for immunotherapy.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Immunology
An-Liang Guo, Jin-Fang Zhao, Lin Gao, Hui-Huang Huang, Ji-Yuan Zhang, Chao Zhang, Jin-Wen Song, Ruo-Nan Xu, Xing Fan, Ming Shi, Yan-Mei Jiao, Fu-Sheng Wang
Summary: The study found that CD11c(+) CD8(+) T cells can effectively control viral replication during HIV-1 infection and have the potential to be used as an immunotherapeutic approach.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Carlos Martinez-Gomez, Marie Michelas, Clara-Maria Scarlata, Anna Salvioni, Carlos Gomez-Roca, Victor Sarradin, Francoise Lauzeral-Vizcaino, Virginie Feliu, Agnes Dupret-Bories, Gwenael Ferron, Jerome Sarini, Christel Devaud, Jean-Pierre Delord, Camille-Charlotte Balanca, Alejandra Martinez, Maha Ayyoub
Summary: This study identified a population of CD4 T cells expressing inhibitory receptors targeted by immunotherapy in the blood of cancer patients. It showed that high proportions of these cells prior to therapy were associated with a response to immunotherapy. The study also found that exhausted CD4 T cells, which contained low proportions of effector cytokine-producing cells, may play a role in clinical responsiveness to immunotherapy.
Article
Immunology
Shilpi Chandra, Gabriel Ascui, Thomas Riffelmacher, Ashu Chawla, Ciro Ramirez-Suastegui, Viankail C. Castelan, Gregory Seumois, Hayley Simon, Mallory P. Murray, Goo-Young Seo, Ashmitaa L. R. Premlal, Benjamin Schmiedel, Greet Verstichel, Yingcong Li, Chia-Hao Lin, Jason Greenbaum, John Lamberti, Raghav Murthy, John Nigro, Hilde Cheroutre, Christian H. Ottensmeier, Stephen M. Hedrick, Li-Fan Lu, Pandurangan Vijayanand, Mitchell Kronenberg
Summary: This study characterized the different populations of MAIT cells in mice and humans using single-cell RNA sequencing and other analyses. The study found that MAIT cells in different organs and tissues exhibit different transcriptomes and metabolic states. The study also identified environmental influences on MAIT cell subsets and function.
SCIENCE IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Elaine Lai-Han Leung, Run-Ze Li, Xing-Xing Fan, Lily Yan Wang, Yan Wang, Zebo Jiang, Jumin Huang, Hu-Dan Pan, Yue Fan, Hongmei Xu, Feng Wang, Haopeng Rui, Piu Wong, Hermi Sumatoh, Michael Fehlings, Alessandra Nardin, Paul Gavine, Longen Zhou, Yabing Cao, Liang Liu
Summary: Immune checkpoint blockade therapy has improved the survival rates of non-small cell lung cancer patients, but only a proportion of them benefit from it. The levels and functional properties of cytotoxic T cells, especially CD8(+)CD101(hi)TIM3(+) cells, determine the response to immunotherapy. Monitoring the peripheral blood samples of NSCLC patients undergoing anti-PD1 therapy can provide insights into the immunological landscape associated with a favorable response.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Sigrun R. Hofmann, Emil Carlsson, Franz Kapplusch, Ana L. Carvalho, Triantafillos Liloglou, Felix Schulze, Susanne Abraham, Sarah Northey, Susanne Russ, Anna E. A. Surace, Nobuya Yoshida, George C. Tsokos, Christian M. Hedrich
Summary: Effector CD4(+) T lymphocytes in psoriasis show increased IL-17 production and decreased expression of IL-2 and PD-1. CREM alpha is linked to low PD-1 levels and can trans-repress gene expression of PD-1 through DNA methylation. These findings suggest a potential molecular pathway for clinical development in psoriasis patients.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Oncology
Bin Zhang, Chun-Mei Wang, Hao-Xiang Wu, Feng Wang, Yang-Yang Chai, Ye Hu, Bing-Jing Wang, Zhou Yu, Rong-Hua Xia, Rui-Hua Xu, Xue-Tao Cao
Summary: In this study, the researchers found that higher expression of MFSD2A was associated with better response to anti-PD-1 immunotherapy in advanced gastric cancer patients. MFSD2A expression was lower in gastric cancer tissues compared to normal tissues, and its overexpression enhanced the efficacy of anti-PD-1 immunotherapy in vivo by reprogramming the tumor microenvironment. MFSD2A inhibited the release of transforming growth factor beta 1 from gastric cancer cells by suppressing cyclooxygenase 2, thus promoting anti-tumor T cell activation.
CANCER COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Lei Li, Jia-Ru Wei, Jun Dong, Qing-Guang Lin, Hong Tang, Yong-Xu Jia, Wanlin Tan, Qing-Yun Chen, Ting-Ting Zeng, Shan Xing, Yan-Ru Qin, Ying-Hui Zhu, Yan Li, Xin-Yuan Guan
Summary: PD-1/PD-L1 blockade therapies have shown significant clinical benefits for advanced cancer patients, but the effectiveness of treatment can be hindered by the up-regulation of laminin gamma 2 (Ln-gamma 2) in the tumor microenvironment, which is transcriptionally activated by transforming growth factor-beta 1 (TGF-beta 1) through JNK/AP1 signaling. Co-administration of a TGF-beta receptor inhibitor and chemotherapy drugs can enhance the anti-tumor activity of anti-PD-1 therapy.
Article
Oncology
Yunmei Dong, Zhen Wang, Fei Mao, Luyao Cai, Hongxia Dan, Lu Jiang, Xin Zeng, Taiwen Li, Yu Zhou, Qianming Chen
Summary: T-cell exhaustion plays a crucial role in oral carcinogenesis, and PD-1 blockade can prevent the progression of oral cancer.
Article
Multidisciplinary Sciences
Kenji Shimizu, Daisuke Sugiura, Il-mi Okazaki, Takumi Maruhashi, Tatsuya Takemoto, Taku Okazaki
Summary: PD-1 preferentially inhibits the expression of TCR-inducible genes when TCR:pMHC affinity is low, demonstrating a qualitative control of T cell responses by suppressing low-affinity T cells. Peptide-MHC affinities and MHC expression levels do not affect PD-1 sensitivity, suggesting that the strength of individual TCR signal is the key determinant of PD-1 sensitivity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Veterinary Sciences
Yulia Makusheva, Soo-Hyun Chung, Aoi Akitsu, Natsumi Maeda, Takumi Maruhashi, Xiao-Qi Ye, Tomonori Kaifu, Shinobu Saijo, Haiyang Sun, Wei Han, Ce Tang, Yoichiro Iwakura
Summary: Clec1A, a member of the C-type lectin receptor family, plays an important role in host defense against Aspergillus fumigatus by recognizing melanin on the fungal surface. This study found that Clec1a(-/-) mice developed milder symptoms in an animal model for multiple sclerosis, suggesting a novel function of Clec1A in the immune system. The reduced production of inflammatory cytokines may be responsible for the amelioration of the disease in Clec1a(-/-) mice.
EXPERIMENTAL ANIMALS
(2022)
Article
Immunology
Tomonori Kaifu, Rikio Yabe, Takumi Maruhashi, Soo-Hyun Chung, Hiroaki Tateno, Noriyuki Fujikado, Jun Hirabayashi, Yoichiro Iwakura
Summary: The inhibitory C-type lectin receptor DCIR interacts with asialo-biantennary N-glycans to negatively regulate osteoclastogenesis and antigen presentation by dendritic cells, which has important implications for autoimmune and bone metabolic diseases.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Immunology
Daisuke Sugiura, Il-mi Okazaki, Takeo K. Maeda, Takumi Maruhashi, Kenji Shimizu, Rieko Arakaki, Tatsuya Takemoto, Naozumi Ishimaru, Taku Okazaki
Summary: The study presents a method to enhance PD-1 function by targeting the PD-L1-CD80 duplex and demonstrates its effectiveness in alleviating symptoms of autoimmune diseases.
Article
Immunology
Takumi Maruhashi, Daisuke Sugiura, Il-Mi Okazaki, Kenji Shimizu, Takeo K. Maeda, Jun Ikubo, Harunori Yoshikawa, Katsumi Maenaka, Naozumi Ishimaru, Hidetaka Kosako, Tatsuya Takemoto, Taku Okazaki
Summary: The study identified stable pMHCII as a functional ligand of LAG-3 in both autoimmune and anti-cancer immunity, playing a crucial role in the suppressive activity of LAG-3.
Review
Immunology
Daisuke Sugiura, Kenji Shimizu, Takumi Maruhashi, Il-mi Okazaki, Taku Okazaki
Summary: PD-1 functions are strictly restricted during T-cell activation by the cis-interactions of PD-L1 and CD80, crucial for optimal T-cell responses. Sensitivity to PD-1 effects in T cells is essentially determined by intrinsic factors.
INTERNATIONAL IMMUNOLOGY
(2021)