Article
Engineering, Biomedical
Xuewei Luo, Guicheng Du, Yufei Long, Mengchao Zheng, Bingye Chen, Weiting Li, Guoliang Yan, Zhongquan Qi, Tianshu Lan
Summary: This study aims to investigate whether DC-derived exosomes (DEX) containing donor antigens (H2b) and high levels of PD-L1 expression can suppress graft rejection. It is demonstrated that DEXPDL1+ can present donor antigens and PD-L1 co-inhibitory signals to H2b-reactive T cells, prolonging the survival of heart grafts from B6 (H2b) mice. Furthermore, DEXPDL1+ treatment provides a new vehicle for presenting co-inhibitory signals to donor-specific T cells.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Oncology
Min Deng, Shao-Hua Li, Xu Fu, Xiao-Peng Yan, Jun Chen, Yu-Dong Qiu, Rong-Ping Guo
Summary: The study revealed a correlation between high expression of PD-L1 in tumors of ICC patients and poor overall survival, while the number of CD8+ T cells was associated with poor overall survival and disease-free survival.
CANCER CELL INTERNATIONAL
(2021)
Article
Chemistry, Multidisciplinary
Jiajia Qi, Tingting Ding, Tiannan Liu, Xin Xia, Shihong Wu, Jiang Liu, Qianming Chen, Dunfang Zhang, Hang Zhao
Summary: A supramolecular hydrogel called inosine-phenylenediboronic-isoguanosine (IPBisoG) has been successfully developed, which demonstrates excellent stability and self-healing properties. The hydrogel can achieve gradual and sequential release of inosine and PD-L1 blocker, enhancing the efficacy of local immunotherapy. The use of the hydrogel also triggers systemic immune responses.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Article
Medicine, General & Internal
Chunyi Shen, Zhen Zhang, Yonggui Tian, Feng Li, Lingxiao Zhou, Wenyi Jiang, Li Yang, Bin Zhang, Liping Wang, Yi Zhang
Summary: The study demonstrated that combining SFN with CAR-T cells enhanced cytotoxicity and antitumor functions by modulating the PD-1/PD-L1 pathway, suggesting a promising strategy for cancer immunotherapy.
Article
Oncology
Guoliang Deng, Lisha Zhou, Binglin Wang, Xiaofan Sun, Qinchang Zhang, Hongqi Chen, Ning Wan, Hui Ye, Xiaoqi Wu, Dongdong Sun, Yang Sun, Haibo Cheng
Summary: This study reveals that Cycloastragenol (CAG) has anti-tumor effects by promoting tumor cell-surface antigen presentation and enhancing the killing function of CD8(+) T cells. Mechanistically, CAG binds to cathepsin B, inhibiting the lysosomal degradation of MHC-I and promoting its aggregation on the cell membrane, which enhances the presentation of tumor antigens. Furthermore, the combination of CAG and PD-1 antibodies enhances the tumor-killing ability of CD8(+) T cells.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Medicine, Research & Experimental
Keywan Mortaezaee, Jamal Majidpoor
Summary: CD8+ T cells play a crucial role in combating cancer, but their infiltration and effector function are often impaired in cancer patients, leading to defective immunity and resistance to immunotherapy. The exclusion and exhaustion of CD8+ T cells are major factors contributing to the limited durability of immune checkpoint inhibitor therapy. Identifying and targeting factors responsible for defective CD8+ T cell infiltration and function could provide a promising supplementary approach in patients undergoing anti-PD-1/PD-L1 therapy. Recent development of bispecific antibodies against PD-(L)1 and key factors within the tumor microenvironment holds great potential in enhancing the effectiveness and safety of cancer immunotherapy.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Immunology
Hongbing Yang, Margarida Rei, Simon Brackenridge, Elena Brenna, Hong Sun, Shaheed Abdulhaqq, Michael K. P. Liu, Weiwei Ma, Prathiba Kurupati, Xiaoning Xu, Vincenzo Cerundolo, Edward Jenkins, Simon J. Davis, Jonah B. Sacha, Klaus Frueh, Louis J. Picker, Persephone Borrow, Geraldine M. Gillespie, Andrew J. McMichael
Summary: HLA-E plays a crucial role in immune response, and vaccine-induced HLA-E-restricted HIV-1-specific T cells have the potential to suppress HIV-1 replication.
SCIENCE IMMUNOLOGY
(2021)
Article
Hematology
Akio Onishi, Shigeo Fuji, Shigehisa Kitano, Akiko Miyagi Maeshima, Kinuko Tajima, Junko Yamaguchi, Ichiro Kawashima, Akihisa Kawajiri, Tomonari Takemura, Ayumu Ito, Takashi Tanaka, Keiji Okinaka, Yoshihiro Inamoto, Saiko Kurosawa, Sung-Won Kim, Wataru Munakata, Dai Maruyama, Kensei Tobinai, Takahiro Fukuda
Summary: This study aims to identify the association between the expression profile of immune checkpoint proteins on ATLL cells and clinical outcomes. The analysis shows that CTLA-4, PD-1, and PD-L1 expressions were adverse prognostic factors in patients with aggressive ATLL.
ANNALS OF HEMATOLOGY
(2022)
Article
Oncology
Topias Karjula, Hanna Elomaa, Anne Niskakangas, Olli Mustonen, Iiris Puro, Teijo Kuopio, Maarit Ahtiainen, Jukka-Pekka Mecklin, Toni T. Seppala, Erkki-Ville Wirta, Eero Sihvo, Juha P. Vayrynen, Fredrik Yannopoulos, Olli Helminen
Summary: The study found that CD3(+) and CD8(+) T-cell density and PD-1/PD-L1 expression have prognostic value in pulmonary metastases of colorectal cancer. T-cell infiltration is higher in pulmonary metastases compared to primary tumors. High CD3(+) and CD8(+) cell density are associated with better survival, while high PD-L1 expression is associated with favorable prognosis.
Article
Immunology
Xiao-Jun Guo, Jia-Cheng Lu, Hai-Ying Zeng, Rong Zhou, Qi-Man Sun, Guo-Huan Yang, Yan-Zi Pei, Xian-Long Meng, Ying-Hao Shen, Peng-Fei Zhang, Jia-Bin Cai, Pei-Xin Huang, Ai-Wu Ke, Ying-Hong Shi, Jian Zhou, Jia Fan, Yi Chen, Liu-Xiao Yang, Guo-Ming Shi, Xiao-Yong Huang
Summary: The study found that in ICC tumors, CTLA-4(+) lymphocyte density was elevated compared to peritumoral hepatic tissues, and patients with high CTLA-4(+) tumor-infiltrating lymphocytes (TILs(CTLA-4 High)) had lower overall survival rates and higher cumulative recurrence rates. High FOXP3(+) TILs (TILs(FOXP3 High)) were associated with poorer prognoses, and the density of CTLA-4(+) TILs was positively correlated with FOXP3(+) TILs. High PD-L1 expression in tumors (Tumor(PD-L1 High)) and/or TILs(CTLA-4 High) were also linked to worse outcomes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Allergy
Zhi-Chao Wang, Yin Yao, Cai-Ling Chen, Cui-Lian Guo, Hong-Xia Ding, Jia Song, Zhe-Zheng Wang, Nan Wang, Xue-Li Li, Bo Liao, Yang Yang, Di Yu, Zheng Liu
Summary: PD-1(high) CXCR5(-)CD4(+) T cells contribute to local immunoglobulin production independent of ectopic lymphoid tissues in nasal polyps.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Oncology
Jie Yang, Jierong Chen, Hu Liang, Yahui Yu
Summary: This study found that PD-L1 is highly expressed in exosomes from the plasma of NPC patients and NPC cells. Exosomal PD-L1 binds to PD-1 on CD8+ T-cell surface, attenuates the cytotoxic function of CD8+ T cells, and promotes immune evasion in NPC.
Article
Biotechnology & Applied Microbiology
Chiara M. M. Cattaneo, Thomas Battaglia, Jos Urbanus, Ziva Moravec, Rhianne Voogd, Rosa de Groot, Koen J. J. Hartemink, John B. A. G. Haanen, Emile E. E. Voest, Ton N. N. Schumacher, Wouter Scheper
Summary: A genetic neoantigen screening system is developed to identify CD4(+) and CD8(+) T cell-recognized neoantigens across patients' complete HLA genotypes.
NATURE BIOTECHNOLOGY
(2023)
Article
Immunology
Kun Hee Lee, So Jung Kim, Jin Seok Woo, Seung Yoon Lee, Jooyeon Jhun, Jeonghyeon Moon, Yoon Ju Jung, Mi-La Cho, Kyo Young Song
Summary: This study found a correlation between immune phenotypes in gastric cancer patients and both normal tissues and peripheral blood, suggesting the potential importance of peripheral blood analysis for prognostic assessment.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Julie Niogret, Helene Berger, Cedric Rebe, Romain Mary, Elise Ballot, Caroline Truntzer, Marion Thibaudin, Valentin Derangere, Christophe Hibos, Lea Hampe, David Rageot, Theo Accogli, Philippe Joubert, Bertrand Routy, James Harker, Frederique Vegran, Francois Ghiringhelli, Fanny Chalmin
Summary: Tfh cells play an important role in antitumor immune response, especially in a CD8(+)-dependent manner, by producing interleukin-21 to support the function of exhausted T cells. Their accumulation in tumor sites and draining lymph nodes is closely associated with treatment efficacy and patient survival.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Margarete M. Karg, Lukas John, Nasrin Refaian, Christian Buettner, Tanja Rottmar, Jonas Sommer, Barbara Bock, Yazid J. Resheq, Bruce R. Ksander, Ludwig M. Heindl, Andreas Mackensen, Jacobus J. Bosch
Summary: This study identifies midkine as a survival factor that drives liver metastasis and therapeutic resistance in uveal melanoma.
MOLECULAR CANCER RESEARCH
(2022)
Article
Hematology
Martin Boettcher, Konstantinos Panagiotidis, Heiko Bruns, Martina Stumpf, Simon Voelkl, Stefanie Geyh, Barbara Dietel, Thomas Schroeder, Andreas Mackensen, Dimitrios Mougiakakos
Summary: BM stroma acts as a protective niche for AML cells, and upregulation of S100A8/A9 after stromal contact increases therapeutic resistance in AML cells.
Article
Multidisciplinary Sciences
Silja Richter, Martin Boettcher, Simon Voelkl, Andreas Mackensen, Evelyn Ullrich, Benedikt Jacobs, Dimitrios Mougiakakos
Summary: This study found that reconstituting immune cells undergo metabolic changes after autologous stem cell transplantation, including increased proliferative activity and upregulation of glycolytic and fatty acid oxidation machinery. This metabolic activation is more pronounced in T-cells of advanced differentiation stages, CD56(bright) NK cells, and CD14(++)CD16(+) intermediate monocytes. Furthermore, persistent metabolic activation is associated with poor disease course in lymphoma patients within the first year following transplantation.
SCIENTIFIC REPORTS
(2022)
Article
Pharmacology & Pharmacy
Johannes Heck, Ann-Kathrin Rath, Katrin Wons, Carsten Schumacher, Anna Kutschenko, Nina Noltemeyer, Sarana Ulaganathan, Luca J. Vossiek, Hemme Hijma, Jeroen van Smeden, Christoph Schroeder, Dirk O. Stichtenoth, Heiner Wedemeyer, Christoph Schindler, Jacobus J. Bosch
Summary: In the midst of the COVID-19 pandemic, support from students in clinical trials for documentation has become crucial. Facing challenges in training due to social-distancing regulations, a panel of experts from Germany and the Netherlands developed a Students' guide to documentation in clinical trials to provide necessary training materials and define quality standards.
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Review
Oncology
Igor Radanovic, Naomi Klarenbeek, Robert Rissmann, Geert Jan Groeneveld, Emilie M. J. van Brummelen, Matthijs Moerland, Jacobus J. Bosch
Summary: This study investigated the utilization of immuno-oncology compounds in clinical trials with healthy volunteers and the evaluation of pharmacodynamic endpoints. The study found that while these trials are not widely conducted, they offer advantages such as early dose selection and prevention of non-therapeutic dosing regimens for cancer patients. The focus is on safety and pharmacodynamic endpoints.
FRONTIERS IN ONCOLOGY
(2022)
Letter
Hematology
Hannah Reimann, Anita N. Kremer, Viktoria Blumenberg, Katja Schmidt, Michael Aigner, Benedikt Jacobs, Nina Eisenhauer, Alina Kaempf, Wolf Roesler, Soraya Kharboutli, Dimitrios Mougiakakos, Vanessa Lang, Christopher Lischer, Pascal Irrgang, Moritz Leppkes, Julio Vera Gonzalez, Gerhard Kroenke, Andreas E. Kremer, Matthias Tenbusch, Heiko Bruns, Thomas Harrer, Fabian Mueller, Georg Schett, Andreas Mackensen, Marion Subklewe, Simon Voelkl
Review
Oncology
Judit Rial Saborido, Simon Voelkl, Michael Aigner, Andreas Mackensen, Dimitrios Mougiakakos
Summary: CAR T cell therapy has revolutionized cancer treatment, but exhaustion and metabolic dysfunction of CAR T cells hinder their efficacy. Tumor cells and their microenvironment can affect T cell metabolism, making metabolic modulation a promising approach to enhance CAR T cell therapy.
Letter
Rheumatology
Christina Bergmann, Fabian Mueller, Joerg H. W. Distler, Andrea-Hermina Gyoerfi, Simon Voelkl, Michael Aigner, Sascha Kretschmann, Hannah Reimann, Thomas Harrer, Nadine Bayerl, Sebastian Boeltz, Andreas Wirsching, Jule Taubmann, Wolf Roesler, Bernd Spriewald, Jochen Wacker, Armin Atzinger, Michael Uder, Torsten Kuwert, Andreas Mackensen, Georg Schett
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Hematology
F. Karl, C. Liang, R. Boettcher-Loschinski, A. Stoll, C. Flamann, S. Richter, C. Lischer, S. Voelkl, B. Jacobs, M. Boettcher, R. Jitschin, H. Bruns, T. Fischer, E. Holler, W. Roesler, T. Dandekar, A. Mackensen, D. Mougiakakos
Summary: Allo-SCT is a curative treatment for hematologic malignancies, relying on the graft-versus-leukemia (GVL) effect of donor T cells. Oxidative stress caused by DNA damage weakens the function of T cells and hampers the GVL effect. High levels of 8-hydroxydeoxyguanosine (8-OHdG), a biomarker for oxidative stress, were associated with enhanced T-cell activation, premature exhaustion, increased relapse risk, and shorter overall survival. Enhancing DNA repair in reconstituting T cells could improve GVL efficacy.
Letter
Medicine, General & Internal
Fabian Mueller, Sebastian Boeltz, Johannes Knitza, Michael Aigner, Simon Voelkl, Soraya Kharboutli, Hannah Reimann, Jule Taubmann, Sascha Kretschmann, Wolf Roesler, Bernhard Manger, Jochen Wacker, Dimitrios Mougiakakos, Samir Jabari, Rolf Schroeder, Michael Uder, Frank Roemer, Gerhard Kroenke, Andreas Mackensen, Georg Schett
Article
Oncology
Rebecca Baur, Franziska Karl, Romy Boettcher-Loschinski, Andrej Stoll, Simon Voelkl, Andreas Giessl, Cindy Flamann, Heiko Bruns, Ursula Schloetzer-Schrehardt, Martin Boettcher, Denis M. Schewe, Thomas Fischer, Regina Jitschin, Andreas Mackensen, Dimitrios Mougiakakos
Summary: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment option for certain hematological malignancies. However, allo-HSCT can also lead to graft-versus-host disease (GvHD) and disease relapse. Recent studies have found that extracellular vesicles (EVs) expressing PD-L1 can suppress T-cell responses and contribute to GvHD and disease relapse in allo-HSCT patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Biology
Lara Goesmann, Nasrin Refaian, Jacobus J. Bosch, Ludwig M. Heindl
Summary: This study aims to provide a detailed understanding of the tumor microenvironment of uveal melanoma (UM) to identify new therapeutic targets. The main findings are that blood vessels are predominantly located in the middle of the tumor, while immune cells are mainly found in the outer section. The high presence of LAG-3 and Galectine-3 in the UM serves as potential therapeutic targets.
Article
Public, Environmental & Occupational Health
Johannes Heck, Christoph Hoener zu Siederdissen, Olaf Krause, Sebastian Schroeder, Martin Schulze Westhoff, Patrick-Pascal Strunz, Carsten Schumacher, Dirk O. Stichtenoth, Jacobus J. Bosch, Thorben Pape, Felix Koop, Benjamin Krichevsky
Summary: ED physicians' decisions on HIV-PEP were highly consistent with national guidelines, and the proportion of patients seeking HIV-PEP in the emergency department was low. It is necessary to train ED physicians on HIV transmission risk assessment and indications/contraindications for HIV-PEP.
INTERNATIONAL HEALTH
(2023)
Article
Biology
Christine Mau, Heike Rudolf, Frederic Strobl, Benjamin Schmid, Timo Regensburger, Ralf Palmisano, Ernst H. K. Stelzer, Leila Taher, Ezzat El-Sherif
Summary: This article addresses the question of how genes are regulated in terms of timing and spatial pattern during development. By studying the AP patterning of the beetle Tribolium, the authors established a model system to investigate dynamic and temporal pattern formation at the enhancer level. They discovered dynamic enhancers and static enhancers that play a balancing role in regulating gene expression during embryonic pattern formation.
Article
Multidisciplinary Sciences
Kai Rejeski, Ariel Perez, Gloria Iacoboni, Viktoria Blumenberg, Veit L. Buecklein, Simon Voelkl, Olaf Penack, Omar Albanyan, Sophia Stock, Fabian Mueller, Philipp Karschnia, Agnese Petrera, Kayla Reid, Rawan Faramand, Marco L. Davila, Karnav Modi, Erin A. Dean, Christina Bachmeier, Michael von Bergwelt-Baildon, Frederick L. Locke, Wolfgang Bethge, Lars Bullinger, Andreas Mackensen, Pere Barba, Michael D. Jain, Marion Subklewe
Summary: Study reveals that intermittent neutrophil recovery after CAR-T cell therapy is associated with better survival outcomes, while aplastic recovery is associated with unfavorable expansion and tumor burden. Serum proteomics analysis shows that prolonged neutrophil aplasia occurs in patients with baseline systemic immune dysregulation, characterized by markers of endothelial dysfunction, increased inflammatory cytokines, macrophage activation, and T cell suppression. The association between neutrophil recovery and survival outcomes highlights critical interactions between host hematopoiesis and the immune state stimulated by CAR-T infusion.