Review
Chemistry, Medicinal
Jinah Yeo, Minkyung Ko, Dong-Hee Lee, Yoon Park, Hyung-seung Jin
Summary: Although immune checkpoint blockade therapies have shown efficacy in multiple cancer indications, only a subset of patients benefit from them, highlighting the need for new approaches. TIGIT and CD226, as regulators of immune cells, have potential applications in cancer immunotherapy as they act on different pathways to modulate immune responses.
Article
Cell Biology
Xiaowen Zhou, Jiangfeng Du, Xiuman Zhou, Xiaoshuang Niu, Wanqiong Li, Chunxia Chen, Sifan Lv, Aijun Wu, Shanshan Gou, Yixuan Sun, Wenjie Zhai, Lu Qiu, Yuanming Qi, Wenshan Zhao, Yanfeng Gao
Summary: The study utilized molecular dynamics simulations and in silico mutagenesis to analyze the interaction between the immune checkpoint molecule TIGIT and its ligand PVR. It identified potential residues for interaction and predicted high affinity PVR mutants that showed enhanced inhibitory effects compared to wild type PVR in cancer immunotherapy.
CELL COMMUNICATION AND SIGNALING
(2021)
Article
Biochemistry & Molecular Biology
Xiuman Zhou, Ling Jiao, Yuzhen Qian, Qingyu Dong, Yixuan Sun, Wei V. Zheng, Wenshan Zhao, Wenjie Zhai, Lu Qiu, Yahong Wu, Hongfei Wang, Yanfeng Gao, Junhui Chen
Summary: Strategies that enhance both innate and adaptive immunity show promising applications in cancer immunotherapy. By targeting both CD47/SIRP alpha and TIGIT/PVR pathways, the anti-hypertensive drug azelnidipine has been found to effectively inhibit tumor growth in preclinical studies.
Article
Immunology
Florence Boissiere-Michot, Marie-Christine Chateau, Simon Thezenas, Severine Guiu, Angelique Bobrie, William Jacot
Summary: In triple negative breast cancer (TNBC), the overexpression of TIGIT and PVR is associated with clinical-pathological features and immune cell infiltration, and their high expression levels may be correlated with longer relapse-free survival.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yu-Xi Lin, Mien-Chie Hung, Jye-Lin Hsu, Jung-Mao Hsu
Summary: This study demonstrates that N-glycosylations of TIGIT are critical for its interaction with PVR, especially the N101 residue. These findings suggest that N-glycosylation sites on TIGIT, particularly residue N101, may be potential targets for PVR/TIGIT immune checkpoint blockade.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Oncology
Xian Shen, Wenyan Fu, Yongpeng Wei, Junle Zhu, Yue Yu, Changhai Lei, Jian Zhao, Shi Hu
Summary: TIGIT-Fc protein promotes tumor immunity by enhancing effector functions of CD8(+) T and NK cells, inducing Th1 development in CD4(+) T cells, and providing potent antibody-dependent cell-mediated cytotoxicity effects, suggesting it as a promising anticancer therapeutic strategy either alone or in combination with other checkpoint receptor blockers.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Oncology
Zhenlin Yang, Yue Peng, Jiachen Xu, Ping Chen, Zhenshan Zhao, Qingyuan Cai, Lin Li, He Tian, Guangyu Bai, Lei Liu, Shugeng Gao, Jie He
Summary: This study evaluated the expression of PVR/TIGIT and PD-L1/PD-1 in lung squamous cell carcinoma (LUSC) and found that co-expression of PVR/PD-L1 was an independent prognostic factor in LUSC patients, suggesting it may serve as a potential predictive biomarker for dual-targeting immunotherapy.
TRANSLATIONAL ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Anand Rotte, Srikumar Sahasranaman, Nageshwar Budha
Summary: Immune checkpoint blockers have improved survival chances in patients with metastatic cancer, but only a subset of patients respond to treatment. Inhibiting TIGIT has shown promise in pre-clinical and early clinical studies, but challenges remain in identifying beneficial patients and obtaining payer coverage.
Review
Oncology
Baokang Wu, Chongli Zhong, Qi Lang, Zhiyun Liang, Yizhou Zhang, Xin Zhao, Yang Yu, Heming Zhang, Feng Xu, Yu Tian
Summary: Immune checkpoint molecules, crucial for controlling immune responses, have been studied extensively and show promise in cancer therapy. A newly discovered cosignaling network involving various immune checkpoint receptors has the potential to enhance cancer immunotherapy by stimulating or inhibiting NK and T cell activation.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Kang Wu, Jun Zeng, Xulian Shi, Jiajia Xie, Yuqing Li, Haoxiang Zheng, Guoyu Peng, Guanghui Zhu, Dongdong Tang, Song Wu
Summary: The study identified a subset of Treg cells with high expression of TIGIT and IL-32 using single-cell sequencing. This subset of Treg cells suppressed the antitumor immune response and promoted bladder cancer metastasis. However, targeting TIGIT reversed immunosuppression, inhibited IL-32 secretion, and suppressed bladder cancer cell metastasis.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Yaping Chen, Hao Huang, Yuan Li, Wenlu Xiao, Yingting Liu, Rongzhang Chen, Yulan Zhu, Xiao Zheng, Changping Wu, Lujun Chen
Summary: Combination immunotherapy based on immune checkpoint inhibitors (ICIs) has shown great success in cancer treatment, and the combination of ablation and immunotherapy has potential for the treatment of liver metastasis of colorectal cancer (CRC). The expression of TIGIT was up-regulated after microwave ablation (MWA), and the combination of MWA and TIGIT blockade significantly promoted the expansion and functions of CD8(+) tumor-infiltrating lymphocytes (TILs) and reshaped myeloid cells in the tumor microenvironment (TME).
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Zhouhong Ge, Maikel P. Peppelenbosch, Dave Sprengers, Jaap Kwekkeboom
Summary: TIGIT is an inhibitory receptor expressed on multiple types of lymphocytes, and the efficacy of TIGIT blockade in cancer immunotherapy is currently under investigation. While single TIGIT blockade has limited anti-tumor efficacy, co-blockade with the PD-1/PD-L1 pathway leads to tumor rejection.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Jonathan D. Worboys, Katherine N. Vowell, Roseanna K. Hare, Ashley R. Ambrose, Margherita Bertuzzi, Michael A. Conner, Florence P. Patel, William H. Zammit, Judit Gali-Moya, Khodor S. Hazime, Katherine L. Jones, Camille Rey, Stipan Jonjic, Tihana Lenac Rovis, Gillian M. Tannahill, Gabriela Dos Santos Cruz De Matos, Jeremy D. Waight, Daniel M. Davis
Summary: This study demonstrates that TIGIT directly inhibits lymphocyte activation independently of CD226 by forming nanoclusters and interacting with TCR.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Ahmed Rishiq, Reem Bsoul, Ophir Pick, Ofer Mandelboim
Summary: The use of antibodies to block inhibitory receptors, such as anti-PD1 and CTLA4, has had a revolutionary impact on cancer treatment. However, there is still a need for additional therapies targeting other inhibitory receptors, as the majority of cancer patients do not respond to checkpoint treatment. In this study, it was found that mouse TIGIT interacts with and is inhibited by mPVR only, and the absence of TIGIT leads to better killing of tumors both in vitro and in vivo.
Review
Immunology
Junpeng Zhao, Liming Li, Huiqi Yin, Xiwei Feng, Qianjin Lu
Summary: Immune checkpoints, such as PD1 and CTLA-4, play a crucial role in immune cell regulation to prevent autoimmunity and maintain tolerance. Targeting these checkpoints has shown significant potential in cancer therapy. TIGIT, as another immune inhibitory receptor, may also be a promising target for both autoimmune diseases and cancers.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Letter
Hematology
Panagiotis Karagiannis, Winfried Alsdorf, Ann-Christin Tallarek, Martin E. Blohm, Jennyfer Oelrich, Jonas S. Waizenegger, Christine Wolschke, Kurt Hecher, Dominique Singer, Carsten Bokemeyer, Walter Fiedler
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Hematology
Laura K. Schmalbrock, Anna Dolnik, Sibylle Cocciardi, Eric Straeng, Frauke Theis, Nikolaus Jahn, Ekaterina Panina, Tamara J. Blaette, Julia Herzig, Sabrina Skambraks, Frank G. Ruecker, Verena Gaidzik, Peter Paschka, Walter Fiedler, Helmut R. Salih, Gerald Wulf, Thomas Schroeder, Michael Luebbert, Richard F. Schlenk, Felicitas Thol, Michael Heuser, Richard A. Larson, Arnold Ganser, Hendrik G. Stunnenberg, Saverio Minucci, Richard M. Stone, Clara D. Bloomfield, Hartmut Doehner, Konstanze Doehner, Lars Bullinger
Summary: This study investigated clonal evolution and resistance mechanisms in FLT3-ITD-mutated AML patients treated with midostaurin, revealing that some patients acquired mutations in signaling pathways, such as MAPK, after becoming FLT3-ITD negative, while others showed no FLT3-ITD mutational changes, suggesting alternative resistance mechanisms or loss of midostaurin inhibitory activity due to inadequate drug levels.
Article
Multidisciplinary Sciences
Thomas Theo Brehm, Marc van der Meirschen, Annette Hennigs, Kevin Roedl, Dominik Jarczak, Dominic Wichmann, Daniel Frings, Axel Nierhaus, Tim Oqueka, Walter Fiedler, Maximilian Christopeit, Christian Kraef, Alexander Schultze, Marc Luetgehetmann, Marylyn M. Addo, Stefan Schmiedel, Stefan Kluge, Julian Schulze zur Wiesch
Summary: Compared to patients with seasonal influenza, COVID-19 patients were younger, had fewer baseline comorbidities, but were more likely to experience severe illness and higher mortality rates.
SCIENTIFIC REPORTS
(2021)
Article
Hematology
Fabio Efficace, Uwe Platzbecker, Massimo Breccia, Francesco Cottone, Paola Carluccio, Prassede Salutari, Eros Di Bona, Erika Borlenghi, Francesco Autore, Luciano Levato, Olimpia Finizio, Valentina Mancini, Stefano D'Ardia, Richard F. Schlenk, Lorella Melillo, Monica Fumagalli, Walter Fiedler, Germana Beltrami, Nicola Stefano Fracchiolla, Massimo Bernardi, Paola Fazi, Ombretta Annibali, Karin Mayer, Maria Teresa Voso, Marco Vignetti
Summary: This study aims to compare the long-term health-related quality of life of APL patients treated with ATRA-ATO vs ATRA chemotherapy, with ATRA-ATO group showing better outcomes in role functioning and dyspnea.
Article
Biochemistry & Molecular Biology
Franziska Brauneck, Elisa Seubert, Jasmin Wellbrock, Julian Schulze zur Wiesch, Yinghui Duan, Tim Magnus, Carsten Bokemeyer, Friedrich Koch-Nolte, Stephan Menzel, Walter Fiedler
Summary: The study identified different NK cell subsets in AML patients, showing that CD56(dim)CD16(-) and CD56(bright)CD16(-) NK cells are predominant, with reduced CD56(dim)CD16(+) NK cells compared to healthy donors. TIGIT, PVRIG, CD39, and CD38 have different clustering patterns on these NK cell subsets and impact NK cell functionality.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Fabian Freisleben, Franziska Modemann, Jana Muschhammer, Hauke Stamm, Franziska Brauneck, Alexander Krispien, Carsten Bokemeyer, Karl N. N. Kirschner, Jasmin Wellbrock, Walter Fiedler
Summary: The study demonstrates that MBZ exhibits strong anti-leukemic effects on AML cells, including sensitizing the cells to chemotherapy and reducing GLI signaling activity by promoting proteasomal degradation of GLI transcription factors. Molecular dynamics simulations reveal a stable binding interaction of MBZ with HSP90. In off-label use, MBZ effectively reduced GLI signaling activity in refractory AML patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Franziska Modemann, Christian Niederwieser, Katja Weisel, Carsten Bokemeyer, Walter Fiedler, Susanne Ghandili
Summary: The study analyzed the clinical courses of COVID-19 and influenza A/B in patients with hematological malignancies, revealing that COVID-19 is more severe in these patients compared to influenza, with higher rates of acute respiratory distress syndrome and virus-associated mortality.
LEUKEMIA & LYMPHOMA
(2022)
Article
Oncology
Andrew H. Wei, Panayiotis Panayiotidis, Pau Montesinos, Kamel Laribi, Vladimir Ivanov, Inho Kim, Jan Novak, Don A. Stevens, Walter Fiedler, Maria Pagoni, Julie Bergeron, Stephen B. Ting, Jing-Zhou Hou, Achilles Anagnostopoulos, Andrew McDonald, Vidhya Murthy, Takahiro Yamauchi, Jianxiang Wang, Brenda Chyla, Yan Sun, Qi Jiang, Wellington Mendes, John Hayslip, Courtney D. DiNardo
Summary: The VIALE-C study compared the safety and efficacy of venetoclax or placebo plus low-dose cytarabine in patients with AML ineligible for intensive chemotherapy. After an additional 6-month follow-up, it was found that venetoclax significantly improved overall survival, complete response rates, and event-free survival compared to placebo, with comparable safety profiles.
BLOOD CANCER JOURNAL
(2021)
Correction
Oncology
Andrew H. Wei, Panayiotis Panayiotidis, Pau Montesinos, Kamel Laribi, Vladimir Ivanov, Inho Kim, Jan Novak, Don A. Stevens, Walter Fiedler, Maria Pagoni, Julie Bergeron, Stephen B. Ting, Jing-Zhou Hou, Achilles Anagnostopoulos, Andrew McDonald, Vidhya Murthy, Takahiro Yamauchi, Jianxiang Wang, Brenda Chyla, Yan Sun, Qi Jiang, Wellington Mendes, John Hayslip, Courtney D. DiNardo
BLOOD CANCER JOURNAL
(2021)
Article
Medicine, General & Internal
Franziska Brauneck, Pauline Weimer, Julian Schulze Zur Wiesch, Katja Weisel, Lisa Leypoldt, Gabi Vohwinkel, Britta Fritzsche, Carsten Bokemeyer, Jasmin Wellbrock, Walter Fiedler
Summary: This study aimed to characterize the phenotype of gamma delta T cells from patients with AML and MM compared to healthy donors. The results showed that BM-resident gamma delta T cells in AML and MM express TIGIT, PD-1, TIM-3 and CD39, suggesting potential for immunotherapeutic strategies by targeting these co-inhibitory receptors on gamma delta T cells.
FRONTIERS IN MEDICINE
(2021)
Article
Infectious Diseases
Franziska Modemann, Steffen Haerterich, Julian Schulze zur Wiesch, Holger Rohde, Nick Benjamin Lindeman, Carsten Bokemeyer, Walter Fiedler, Susanne Ghandili
Summary: Tigecycline treatment is more effective in combating infections in leukemia patients compared to standard treatment, resulting in lower rates of sepsis and infection-associated mortality.
Article
Oncology
Susanne Ghandili, Philipp H. von Kroge, Marcel Simon, Frank O. Henes, Holger Rohde, Armin Hoffmann, Nick Benjamin Lindeman, Carsten Bokemeyer, Walter Fiedler, Franziska Modemann
Summary: Infections pose a major threat to leukemia patients, even with broad-spectrum anti-infective treatment. Approximately half of all patients with acute leukemia still have detectable pathogens in bronchoalveolar samples. However, these detections do not frequently lead to changes in treatment.
Article
Cell Biology
Pauline Weimer, Jasmin Wellbrock, Tabea Sturmheit, Leticia Oliveira-Ferrer, Yi Ding, Stephan Menzel, Marius Witt, Louisa Hell, Barbara Schmalfeldt, Carsten Bokemeyer, Walter Fiedler, Franziska Brauneck
Summary: This study found a high prevalence of V δ1 T cells in the malignant ascites lymphocytes (MALs) and tumor infiltrating lymphocytes (TILs) of ovarian cancer patients. These cells exhibited different differentiation states, and V δ1 T cells in TILs showed the highest levels of expression for TIGIT, PD-1, and CD39, which provides hope for therapeutic strategies based on V δ1 T cells and these receptors.
Review
Oncology
Franziska Modemann, Susanne Ghandili, Stefan Schmiedel, Katja Weisel, Carsten Bokemeyer, Walter Fiedler
Summary: This article presents a review of the current literature on adult patients with acute leukemia (AL) infected with SARS-CoV-2. The mortality rate associated with SARS-CoV-2 in adult AL patients ranges from 20-52%, with acute myeloid leukemia (AML) patients having a particularly high COVID-19-related mortality. Most of the available data pertain to the pre-vaccination era and variants before Omicron. Treatment delay does not appear to increase the risk of relapse in AL patients, but therapy discontinuation is associated with worse outcomes in AML patients. Current recommendations suggest delaying systemic AL treatment in SARS-CoV-2-positive patients until they test negative, if immediate treatment is not required. Vaccination is recommended for all AL patients, with reported antibody responses ranging from 80-96%. Seronegative patients should also receive prophylactic administration of anti-SARS-CoV-2 monoclonal antibodies. Early antiviral therapy is recommended for AL patients infected with SARS-CoV-2 to prevent disease progression and expedite virus elimination.
Article
Hematology
Nils W. Engel, Jochim Reinert, Nora M. Borchert, Victoria Panagiota, Razif Gabdoulline, Felicitas Thol, Michael Heuser, Walter Fiedler
Summary: Isolated myeloid sarcoma is a rare malignancy where tumors form in various locations while the bone marrow remains unaffected. Clonal evolution and clonal hematopoiesis of indeterminate potential were observed in some cases with detectable mutations. Clinical presentation of patients suggested possible extramedullary blast trafficking to distal sites, avoiding the bone marrow.
ANNALS OF HEMATOLOGY
(2021)
