Review
Cell Biology
Adam Mor, Marianne Strazza
Summary: The emergence of immune checkpoint inhibitors has transformed the treatment of tumors, but challenges still remain such as non-responsive patients and immune-related adverse events. This review aims to bridge the gap between our understanding of PD-1 signaling, ICI-induced adverse events, and autoimmune diseases, and propose new therapeutic strategies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Immunology
Aditya Arra, Holger Lingel, Mandy Pierau, Monika C. C. Brunner-Weinzierl
Summary: PD-1 plays a crucial role in suppressing the differentiation and function of Tc17 cells, and blockade of PD-1 can effectively enhance tumor immune response. PD-1 signaling inhibits the expression of IL-17 and related transcription factors in Tc17 cells, and also suppresses the expression of IL-21 and IL-23 receptors specific to Tc17 cells. Inhibition of PD-1 leads to the conversion of Tc17 cells into Tc1 cells, which possess tumor control characteristics.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Karla M. Viramontes, Emily N. Neubert, Julia M. DeRogatis, Roberto Tinoco
Summary: PSGL-1 plays multiple regulatory roles in exhausted T cells, limiting their expansion in tumors and persistently infected hosts. It is also necessary for the long-term maintenance and optimal differentiation of exhausted T cells into specific subsets. Additionally, PSGL-1 restrains the reinvigoration potential of exhausted CD4(+) and CD8(+) T cells during ICI therapy. Targeting PSGL-1 may have therapeutic potential alone or in combination with other ICIs to reinvigorate exhausted T cells in patients with chronic infections or cancer.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Fanny Polesso, Michael W. Munks, Katherine H. Rott, Savannah Smart, Ann B. Hill, Amy E. Moran
Summary: Therapeutic antibodies blocking PD-1/PD-L1 interaction have shown success in cancer treatment, but different antibody isotypes and species can impact the outcome. This study demonstrates that anti-PD-1 therapy in mice may lead to unintended target cell depletion and emphasizes the importance of considering antibody clones in experimental design and interpretation. Competing anti-PD-1 clones can be used to detect PD-1-expressing cells despite the presence of blocking antibodies, providing valuable insights for future studies.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Antonia N. Policheni, Charis E. Teh, Alissa Robbins, Selma Tuzlak, Andreas Strasser, Daniel H. D. Gray
Summary: By investigating compound mutant mice, researchers discovered a cooperative relationship between AIRE and PD-1, the loss of which can lead to spontaneous and lethal autoimmune disease. These findings have important implications for our understanding of how immune checkpoint blockade and defects in central tolerance can synergize to elicit autoimmune diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
David Escors, Ana Bocanegra, Luisa Chocarro, Ester Blanco, Sergio Pineiro-Hermida, Maider Garnica, Leticia Fernandez-Rubio, Ruth Vera, Hugo Arasanz, Grazyna Kochan
Summary: PD-L1/PD-1 blockade immunotherapy has revolutionized cancer treatment, but its mechanisms and effectiveness are still not fully understood. This article reviews the evidence supporting the role of CD4 T cells in anti-tumor immunity and their potential as predictors of response to PD-L1/PD-1 blockade immunotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Kimberly Tang, Bruce C. Tiu, Guihong Wan, Shijia Zhang, Nga Nguyen, Bonnie Leung, Alexander Gusev, Kerry L. Reynolds, Shawn G. Kwatra, Yevgeniy R. Semenov
Summary: There is no increased risk of mortality for cancer patients with pre-existing autoimmune diseases when treated with immune checkpoint inhibitors (ICIs). In fact, a history of Hashimoto's disease and vitiligo is associated with decreased mortality.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2022)
Article
Immunology
Zihan Zhao, Siyang Liu, Rui Sun, Wenjie Zhu, Yulin Zhang, Tianyao Liu, Tianhang Li, Ning Jiang, Hongqian Guo, Rong Yang
Summary: Bladder cancer is a highly malignant tumor with limited improvement in prognosis and survival rates. Immune checkpoint inhibitors have revolutionized the treatment of bladder cancer, but their clinical application is limited by low response rates. This study investigated the combination of oxaliplatin and anti-PD-1 inhibitor in bladder cancer mouse models and found that this combination therapy was more efficient than medication alone.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Ning Shi, Yangyihua Zhou, Yujun Liu, Ran Zhang, Xingjun Jiang, Caiping Ren, Xiang Gao, Longlong Luo
Summary: In this study, a novel bispecific antibody YG-003D3 targeting PD-1 and LAG-3 was designed, showing strong anti-tumor activity by activating immune cells more effectively. The antibody maintained similar affinity and thermal stability to the parental antibody, and could target multiple cells simultaneously to release the 'brake system of immune checkpoints'. The antibody also exhibited better ability to activate PBMC and alter the proportion of immune cells in the tumor microenvironment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Markus Zeisbrich, Nina Chevalier, Bettina Sehnert, Marta Rizzi, Nils Venhoff, Jens Thiel, Reinhard E. Voll
Summary: This study reveals a deficiency of the immunoinhibitory checkpoint PD-L1 in monocytes from AAV patients. Reduced expression of CMTM6 leads to increased lysosomal degradation of PD-L1, providing insufficient negative signaling to T cells. Correcting this defect by targeting lysosomal function may offer a novel strategy for treating AAV.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Tom Hofland, Anne W. J. Martens, Jaco A. C. van Bruggen, Renate de Boer, Sjoerd Schetters, Ester B. M. Remmerswaal, Frederike J. Bemelman, Mark-David Levin, Adriaan D. Bins, Eric Eldering, Arnon P. Kater, Sanne H. Tonino
Summary: The study identified CXCR5(+)PD-1(+) CD8 T cells in human peripheral blood and LN, which could play a crucial role during PD-1 ICB, indicating their potential importance in human immune therapy.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yun-Hui Jeon, Namhee Lee, Jiyoon Yoo, Solchan Won, Suk-kyung Shin, Kyu-Hwan Kim, Jun-Gyu Park, Min-Gang Kim, Hang-Rae Kim, Keunhee Oh, Dong-Sup Lee
Summary: Oncolytic virotherapy can enhance tumor-specific T cell responses and decrease immunosuppression, converting cold tumors into hot tumors and leading to response to combination PD-1 treatment. In addition, oncolytic vaccinia virus can induce long-term durable anticancer immunity.
Article
Pharmacology & Pharmacy
Tawit Suriyo, Mayuree Fuangthong, Charlermchai Artpradit, Teerapat Ungtrakul, Thaniya Sricharunrat, Fatma Taha, Jutamaad Satayavivad
Summary: The PD-L1/PD-1 axis inhibits T-cell-mediated immune response in intrahepatic cholangiocarcinoma (CCA), leading to immune evasion. Using an anti-PD-1 antibody may be a potential therapeutic strategy, but further research is needed for validation.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Oncology
Wenhua Xu, Linqing Wu, Mei Xu, Jia Luo, Gang Chen
Summary: Alcohol consumption in women increases the risk of breast cancer, with ethanol being the main causal factor. This study using a mouse model found that ethanol exposure enhances mammary tumor formation and inhibits T cell anti-tumor function, while inhibition of the PD-1/PD-L1 pathway can mitigate ethanol-enhanced tumorigenesis.
FRONTIERS IN ONCOLOGY
(2022)
Article
Rheumatology
Eriho Yamaguchi, Keiichiro Kadoba, Ryu Watanabe, Takeshi Iwasaki, Koji Kitagori, Shuji Akizuki, Kosaku Murakami, Ran Nakashima, Motomu Hashimoto, Masao Tanaka, Akio Morinobu, Hajime Yoshifuji
Summary: This study compared the clinical characteristics and outcomes between patients with giant cell arteritis (GCA) with or without large vessel involvement (LVI). The results showed that GCA without LVI had more active disease, severer vascular damage, and worse survival.
MODERN RHEUMATOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Mengyuan Li, Yimei Lai, Binfeng Chen, Chaohuan Guo, Mianjing Zhou, Siyuan Zhao, Shuyi Wang, Jin Li, Niansheng Yang, Hui Zhang
Summary: This study identifies nicotinamide phosphoribosyltransferase (NAMPT) as a key regulator of IFNy production in CD4+ T cells in lupus nephritis (LN). NAMPT promotes aerobic glycolysis and mitochondrial respiration, leading to increased IFNy production. Inhibition of NAMPT suppresses IFNy production and reduces kidney damage in lupus mice.
Editorial Material
Critical Care Medicine
Richard H. Kimura, Husham Sharifi, Bin Shen, Gerald J. Berry, H. Henry Guo
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Immunology
Huimin Zhang, Rohit R. Jadhav, Wenqiang Cao, Isabel N. Goronzy, Tuantuan V. Zhao, Jun Jin, Shozo Ohtsuki, Zhaolan Hu, Jose Morales, William J. Greenleaf, Cornelia M. Weyand, Jorg J. Goronzy
Summary: Immune aging is a combination of cellular defects and low-inflammatory state. TCR activation in older adults accelerates remodeling of the epigenome and induces transcription factor networks favoring effector cell differentiation. Reduced HELIOS expression directs T cell fate decisions toward inflammatory effector cells that infiltrate tissue in older adults.
Article
Immunology
Jason D. Goldman, Stephanie M. Pouch, Ann E. Woolley, Sarah E. Booker, Courtney T. Jett, Cole Fox, Gerald J. Berry, Kelly E. Dunn, Chak-Sum Ho, Michelle Kittleson, Dong Heun Lee, Deborah J. Levine, Charles C. Marboe, Gary Marklin, Raymund R. Razonable, Sarah Taimur, Helen S. Te, Judith A. Anesi, Cynthia E. Fisher, Marty T. Sellers, Anil J. Trindade, R. Patrick Wood, Lorenzo Zaffiri, Marilyn E. Levi, David Klassen, Marian G. Michaels, Ricardo M. La Hoz, Lara Danziger-Isakov
Summary: This study compared organ utilization and recipient outcomes between SARS-CoV-2 nucleic acid test-positive (NAT+) and negative (NAT-) donors. The results showed lower organ utilization for NAT+ donors, but similar short-term outcomes of death and graft loss, with no SARS-CoV-2 transmission events.
TRANSPLANT INFECTIOUS DISEASE
(2023)
Article
Immunology
Ryu Watanabe, Kosaku Murakami, Toshimitsu Fujisaki, Hiromu Ito, Koichi Murata, Wataru Yamamoto, Takayuki Fujii, Hideo Onizawa, Akira Onishi, Masao Tanaka, Akio Morinobu, Motomu Hashimoto
Summary: The long-term effects of tocilizumab on joint destruction in rheumatoid arthritis patients were evaluated in this study. The results showed that patients who achieved structural remission were relatively younger, had a higher proportion of anti-citrullinated protein antibody positivity, and lower levels of C-reactive protein and erythrocyte sedimentation rate. Multivariate logistic regression analysis demonstrated that the baseline erythrocyte sedimentation rate level was significantly associated with structural remission.
IMMUNOLOGICAL MEDICINE
(2023)
Article
Cell Biology
Qin Zeng, Shuyi Wang, Mengyuan Li, Shuang Wang, Chaohuan Guo, Xinyuan Ruan, Ryu Watanabe, Yimei Lai, Yuefang Huang, Xiaoyu Yin, Chuanzhao Zhang, Binfeng Chen, Niansheng Yang, Hui Zhang
Summary: In this study, researchers find that spleen Fibroblastic Reticular Cells (FRCs) release acetylcholine (ACh) which is a key factor in controlling autoreactive B cell responses in Systemic Lupus Erythematosus (SLE). CD36-mediated lipid uptake in B cells enhances mitochondrial oxidative phosphorylation in SLE. The inhibition of fatty acid oxidation reduces autoreactive B cell responses and improves SLE in lupus mice. The ablation of CD36 in B cells impairs lipid uptake and autoreactive B cell differentiation during autoimmune induction. Mechanistically, spleen FRC-derived ACh promotes lipid influx and generation of autoreactive B cells through CD36.
Article
Gastroenterology & Hepatology
Aaron Yeoh, Chiraag Kulkarni, Emily Ryan, Gerald Berry, George Triadafilopoulos
DIGESTIVE DISEASES AND SCIENCES
(2023)
Letter
Immunology
Sarah E. Booker, Courtney Jett, Cole Fox, Judith A. Anesi, Gerald J. Berry, Kelly E. Dunn, Cynthia E. Fisher, Jason D. Goldman, Chak-Sum Ho, Michelle Kittleson, Dong Heun Lee, Deborah J. Levine, Charles C. Marboe, Gary Marklin, Carlos Martinez, Raymund R. Razonable, Marty T. Sellers, Sarah Taimur, Helen S. Te, Anil J. Trindade, R. Patrick Wood, Ann E. Woolley, Lorenzo Zaffiri, David K. Klassen, Marian G. Michaels, Stephanie M. Pouch, Lara Danziger-Isakov, Ricardo M. La Hoz
TRANSPLANT INFECTIOUS DISEASE
(2023)
Article
Cell Biology
Wenqiang Cao, Ines Sturmlechner, Huimin Zhang, Jun Jin, Bin Hu, Rohit R. Jadhav, Fengqin Fang, Cornelia M. Weyand, Jorg J. Goronzy
Summary: Naive CD4+ T cells are more resistant to age-related loss than naive CD8+ T cells, indicating the presence of mechanisms that preferentially protect naive CD4+ T cells during aging. The study reveals that TRIB2 is more abundant in naive CD4+ T cells and suppresses AKT activation to prevent quiescence exit. Loss of TRIB2 leads to increased AKT activity, accelerated proliferation, and differentiation in response to IL-7. Transcription of TRIB2 is controlled by lineage-determining transcription factors ThPOK and RUNX3. Deletion of Zbtb7b (encoding ThPOK) and Cbfb (obligatory RUNT cofactor) attenuates the difference in lymphopenia-induced proliferation between naive CD4+ and CD8+ cells. In older adults, decreased expression of ThPOK and TRIB2 in naive CD4+ T cells causes loss of naivety. These findings highlight the importance of TRIB2 in regulating T cell homeostasis and provide insights into the differential resilience of CD8+ T cells to age-related changes.
Article
Cell Biology
Shozo Ohtsuki, Chenyao Wang, Ryu Watanabe, Hui Zhang, Mitsuhiro Akiyama, Melanie C. Bois, Joseph J. Maleszewski, Kenneth J. Warrington, Gerald J. Berry, Jorg J. Goronzy, Cornelia M. Weyand
Summary: Loss of function of inhibitory immune checkpoints can lead to autoimmune disease, such as giant cell arteritis (GCA). In this study, a defective CD155-CD96 immune checkpoint was found in GCA patients, resulting in the retention of CD155 in the endoplasmic reticulum (ER) of macrophages. Antigen-presenting cells with low CD155 expression induced the expansion of tissue invasive CD4+CD96+ T cells that released interleukin-9 (IL-9). The dysregulated immune response caused vessel wall destruction, which could be suppressed by anti-IL-9 antibodies in a GCA mouse model.
CELL REPORTS MEDICINE
(2023)
Editorial Material
Urology & Nephrology
Francesco Peyronel, Augusto Vaglio
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Medicine, Research & Experimental
George S. Liu, Gerald J. Berry, Scott G. Soltys, Nikolas H. Blevins
Summary: This is a case report of a rare glomangiopericytoma presenting as a mass in the middle ear, involving the ossicles and extending into the mastoid antrum without bony destruction. The patient underwent three surgeries and stereotactic radiosurgery, achieving local control 12 months after radiation. Facial nerve function and hearing were preserved. This is the first report of a glomangiopericytoma presenting as a primary temporal bone lesion. Treatment with surgery and stereotactic radiosurgery is an effective approach for achieving local control and functional preservation.
Article
Cell Biology
Yuki Sato, Abhinav Jain, Shozo Ohtsuki, Hirohisa Okuyama, Ines Sturmlechner, Yoshinori Takashima, Kevin-Phu C. Le, Melanie C. Bois, Gerald J. Berry, Kenneth J. Warrington, Jorg J. Goronzy, Cornelia M. Weyand
Summary: Autoimmune vasculitis can lead to serious complications and is often refractory to immunosuppressive therapy. Recent studies have identified a CD4(+) T cell population with stem cell-like features in vasculitic arteries, which plays a crucial role in maintaining granulomatous infiltrates and promoting chronic inflammation. Targeting these stem-like CD4(+) T cells may provide new therapeutic strategies for autoimmune vasculitis.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Letter
Rheumatology
Ryu Watanabe, Motomu Hashimoto, Akio Morinobu
ANNALS OF THE RHEUMATIC DISEASES
(2023)