Article
Oncology
Maud Plaschka, Valentin Benboubker, Maxime Grimont, Justine Berthet, Laurie Tonon, Jonathan Lopez, Myrtille Le-Bouar, Brigitte Balme, Garance Tondeur, Arnaud de la Fouchardiere, Lionel Larue, Alain Puisieux, Yenkel Grinberg-Bleyer, Nathalie Bendriss-Vermare, Bertrand Dubois, Christophe Caux, Stephane Dalle, Julie Caramel
Summary: This study reveals that ZEB1 expression in melanoma cells is associated with decreased CD8(+) T cell infiltration, leading to tumor immune evasion and resistance to immune checkpoint blockade. ZEB1 directly represses the secretion of T cell-attracting chemokines, such as CXCL10, and targeting ZEB1 may enhance the efficacy of immunotherapy in melanoma.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Immunology
Yihao Mao, Yuqiu Xu, Jiang Chang, Wenju Chang, Yang Lv, Peng Zheng, Zhiyuan Zhang, Zhiqiang Li, Qi Lin, Wentao Tang, Dexiang Zhu, Meiling Ji, Guodong He, Qingyang Feng, Jianmin Xu
Summary: This study explores the immune phenotypes and immune escape mechanisms of colorectal cancer (CRC) and provides inspiration for further research on CRC immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Neurosciences
Xu Guo, Gang Wang
Summary: This review explores the mechanisms by which glioma cells suppress antitumor immune responses and produce escape, with a focus on immune cell differentiation and function in the tumor microenvironment. A deeper understanding of immune response and evasion mechanisms in glioma is needed to develop more effective treatment modalities.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Review
Oncology
Yunbo He, Jinliang Huang, Qiaorong Li, Weiping Xia, Chunyu Zhang, Zhi Liu, Jiatong Xiao, Zhenglin Yi, Hao Deng, Zicheng Xiao, Jiao Hu, Huihuang Li, Xiongbing Zu, Chao Quan, Jinbo Chen
Summary: The status and composition of gut microbiota have a profound impact on human antitumor immunity by influencing immune cells and inflammatory factors. Protecting and optimizing gut microbiota can improve the efficacy of immunotherapy, bringing new hope for cancer treatment.
Review
Pharmacology & Pharmacy
Chunping Liu, Dongyue He, Longmei Li, Shihui Zhang, Lei Wang, Zhijin Fan, Yichao Wang
Summary: This review aims to explore the role of extracellular vesicles (EVs) in immune escape in pancreatic cancer (PC) and their potential in cancer immunotherapy. Despite significant progress in clinical trials of immunotherapies for various cancers, the effectiveness of immunotherapy is still low in PC, possibly due to immune evasion mechanisms. Therefore, investigating the role of EVs in immune escape in PC is crucial for developing more effective immunotherapies.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Yubiao Lin, Kaida Huang, Zhezhen Cai, Yide Chen, Lihua Feng, Yingqin Gao, Wenhui Zheng, Xin Fan, Guoqin Qiu, Jianmin Zhuang, Shuitu Feng
Summary: This study provides assistance for personalized therapy for gastric cancer through exosome-based classification. The results show that exosome-relevant phenotype B has a poorer prognosis, an inflamed tumor microenvironment, and higher responses to the anti-CTLA4 inhibitor. The exosome-based gene signature can independently and accurately predict gastric cancer prognosis, which is linked to stromal activation and immunosuppression.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Marit J. van Elsas, Camilla Labrie, Anders Etzerodt, Pornpimol Charoentong, Jordi J. C. van Stigt Thans, Thorbald Van Hall, Sjoerd H. van der Burg
Summary: A small population of CD163(hi) tissue-resident macrophages is identified to be responsible for primary and secondary resistance against T-cell-based immunotherapies. While these CD163(hi) M2 macrophages are resistant to Csf1r-targeted therapies, in-depth characterization and identification of the underlying mechanisms driving immunotherapy resistance allows the specific targeting of this subset of macrophages, thereby creating new opportunities for therapeutic intervention with the aim to overcome immunotherapy resistance.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Neurosciences
Shi Feng, Yonggang Zhang, Hua Zhu, Zhihong Jian, Zhi Zeng, Yingze Ye, Yina Li, Daniel Smerin, Xu Zhang, Ning Zou, Lijuan Gu, Xiaoxing Xiong
Summary: This study investigates the effect of cuproptosis on the immune microenvironment and its predictive power in prognosis and immunotherapy response in gliomas. The findings suggest that high levels of cuproptosis in glioma patients are associated with worse prognosis and immunosuppression. A cuproptosis-related signature, named CuproScore, shows strong prognostic and predictive ability for response to immunotherapy and chemotherapy drug sensitivity.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Oncology
Wei Zhang, Xin-yu Qiao, Qian Li, Chun Cui, Chen-meng Qiao, Yan-qin Shen, Wei-jiang Zhao
Summary: TRPM8 is strongly associated with tumor physiology and immunity and has the potential to be a treatment target or biomarker for determining the prognosis of a specific type of cancer.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hiroki Mukai, Nagisa Miki, Hikari Yamada, Haruka Goto, Taiko Kawakami, Akari Suzuki, Kazuhiko Yamamoto, Yusuke Nakanishi, Kyoko Takahashi
Summary: This study identified a new immune-escape mechanism for tumors involving the secretion of Panx1-dependent extracellular traps by apoptotic tumor cells. Inhibition of this mechanism may offer a new therapeutic target for cancer treatment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Danilo Galizia, Silvia Minei, Elena Maldi, Giovanna Chila, Alessio Polidori, Marco Carlo Merlano
Summary: Most head and neck squamous cell carcinomas (HNSCCs) are caused by lifestyle factors such as smoking or virus infections including HPV and EBV. Despite improvements in surgical, radiation, and chemotherapy treatments, recurrent/metastatic (R/M) disease remains a challenge in clinical practice. While immunotherapy has shown promise in a small percentage of patients, the majority still do not benefit. Recent preclinical and clinical studies have explored the HNSCC tumor immune microenvironment (TIME) and identified important differences between smoking-associated and virus-associated HNSCCs, which impact immune escape mechanisms and response to immunotherapy.
Review
Immunology
Ricardo M. Sainz, Jorge Humberto Rodriguez-Quintero, Maria Constanza Maldifassi, Brendon M. Stiles, Erik Wennerberg
Summary: While the expression of P2X7 receptor on tumor cells promotes cancer growth and metastasis, its expression by the host immune system is essential for coordinating immune responses against cancer. However, there are conflicting roles of P2X7 receptor in regulating immune responses to tumors, making it challenging to develop P2X7 receptor modulators for cancer treatment. This review discusses the prognostic value of P2X7 receptor in cancer, current approaches targeting P2X7 receptor in tumor models, and how tumors manipulate immune responses through P2X7 receptor to promote immune escape. Alternative strategies to overcome tumor immune escape via P2X7 receptor for enhancing immunotherapeutic strategies in cancer patients are also discussed.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Zaoqu Liu, Yuyuan Zhang, Chengcheng Shi, Xueliang Zhou, Kaihao Xu, Dechao Jiao, Zhenqiang Sun, Xinwei Han
Summary: The study identified three distinct tumor immunological microenvironment (TIME) phenotypes in hepatocellular carcinoma, each with different clinical outcomes, immune escape mechanisms, and genomic alterations. These findings may offer strategies to improve the efficacy of immunotherapy. Time index (TI) was proposed as a novel prognostic and immunotherapeutic signature to guide personalized immunotherapy and clinical management of HCC.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Review
Cell Biology
Claudia Galassi, Martina Musella, Nicoletta Manduca, Ester Maccafeo, Antonella Sistigu
Summary: Cancer stem cells (CSCs) have the ability to evade immune surveillance and are located at the apex of tumor aggressiveness and therapy resistance. Understanding the immunobiology of CSCs is crucial for identifying new therapeutic opportunities in cancer treatment.
Review
Immunology
Agnete S. T. Engelsen, Maria L. Lotsberg, Raefa Abou Khouzam, Jean-Paul Thiery, James B. Lorens, Salem Chouaib, Stephane Terry
Summary: The development and implementation of Immune Checkpoint Inhibitors (ICI) have significantly improved the survival of metastatic cancer patients, but low response rates and limited understanding of mechanisms regulating anti-tumor immunity remain major concerns. AXL, a receptor tyrosine kinase, has been identified as a potential molecular target to overcome therapy resistance and improve ICI efficacy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Stefano Testa, Ole A. W. Haabeth, Timothy R. Blake, Trevor J. Del Castillo, Debra K. Czerwinski, Ranjani Rajapaksa, Paul A. Wender, Robert M. Waymouth, Ronald Levy
Summary: Charge-altering releasable transporters (CARTs) containing fingolimod were synthesized to enhance mRNA delivery and expression in lymphocytes through ligand-receptor interaction. The fingolimod-conjugated CARTs showed superior transfection of activated T and B lymphocytes in vitro and increased mRNA delivery to specific cell populations in the spleen in vivo.
Article
Oncology
Peter McLaughlin, Antonio J. Grillo-Lopez, Brain K. Link, Ronald Levy, Myron S. Czuczman, Michael E. Williams, Meyer R. Heyman, Isabelle Bence-Bruckler, Christine A. White, Fernando Cabanillas, Vinay Jain, Anthony D. Ho, John Lister, Key Wey, David Shen, Brain K. Dallaire
Summary: In this study, the chimeric anti-CD20 antibody IDEC-C2B8 was used to treat patients with relapsed low grade or follicular lymphoma. The response rate was 48%, comparable to single-agent cyto-toxic chemotherapy. Further research is needed to determine the efficacy of this agent and its potential use in combination with standard chemotherapy.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Biochemical Research Methods
Timothy R. Blake, Ole A. W. Haabeth, Adrienne Sallets, Rebecca L. McClellan, Trevor J. Del Castillo, Jose G. Vilches-Moure, Wilson C. Ho, Paul A. Wender, Ronald Levy, Robert M. Waymouth
Summary: Targeted delivery of nucleic acid therapeutics to the lungs shows promise for treating pulmonary diseases. New lysine-derived CART-mRNA complexes (K-CARTs/mRNA) demonstrate selective protein expression in the lungs without additives or targeting ligands. The ability to direct protein expression selectively in the spleen or lungs by simple changes to the CART structure opens new opportunities in research and gene therapy.
BIOCONJUGATE CHEMISTRY
(2023)
Review
Hematology
Robert Zeiser, Yi-Bin Chen, Nader N. Youssef, Francis Ayuk
Summary: Acute graft-versus-host disease (aGVHD) is a severe complication after allogeneic haematopoietic cell transplantation, with gastrointestinal (GI) tract involvement (GI aGVHD) being a major cause of morbidity and mortality. Despite systemic steroids being the standard treatment for aGVHD, around 50% of patients do not respond to steroids, leading to poor outcomes. This review discusses the role of glucagon-like peptide 2 (GLP-2) in protecting and maintaining GI epithelial cells, as well as the potential use of the GLP-2 analogue apraglutide as an adjunctive treatment for GI aGVHD.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Robert Zeiser
Summary: This study summarizes the treatment approach for chronic graft-versus-host disease (cGVHD) and finds that adding ibrutinib to first-line therapy is not recommended. Currently, glucocorticoid monotherapy remains the standard treatment for cGVHD.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Niroz Abu-Saleh, Chiung-Chi Kuo, Wei Jiang, Ronald Levy, Shoshana Levy
Summary: Metastases are decreased in CD81KO mice. Moreover, a specific anti-CD81 antibody, 5A6, can inhibit metastasis in vivo and invasion and migration in vitro. Removing cholesterol or the intracellular domains of CD81 doesn't affect 5A6's inhibitory effect. The uniqueness of 5A6 is attributed to its recognition of a specific epitope on CD81's large extracellular loop. Finally, several CD81 membrane-associated partners, such as integrins and transferrin receptors, may contribute to the antimetastatic attributes of 5A6.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Editorial Material
Clinical Neurology
Robert Zeiser, Marco Prinz
Summary: This scientific commentary discusses the neurological effects of immune checkpoint inhibitor-related neurotoxicity, based on the study by Farina et al.
BRAIN COMMUNICATIONS
(2023)
Article
Biophysics
Norbert Hollaender, Ekkehard Glimm, Jennifer Gauvin, Tommaso Stefanelli, Robert Zeiser
Summary: Overall response rate (ORR) and best overall response rate (BOR) are commonly used as key endpoints to evaluate the efficacy of treatments for chronic graft versus host disease (cGvHD). This study introduced the probability of being in response (PBR) as a novel measure and demonstrated that Ruxolitinib showed better response rates and longer response duration compared to the best available therapy (BAT). PBR is a clinically interpretable measurement and can be a useful endpoint for assessing cGvHD treatments.
BONE MARROW TRANSPLANTATION
(2023)
Review
Hematology
Viktor Fetsch, Robert Zeiser
Summary: The use of CAR T cells has greatly impacted the treatment of B-cell malignancies, but it has not yet been widely adopted for myeloid malignancies like AML or MPNs. This article discusses the challenges in using CAR T cells for myeloid malignancies and presents novel approaches to enhance their efficacy and reduce toxicity.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Radu-Florian Gherman, Sophie Ewald, Gabriele Ihorst, Tim Strussmann, Robert Zeiser, Ralph Waesch, Hartmut Bertz, Daiana Stolz, Justus Duyster, Juergen Finke, Reinhard Marks, Monika Engelhardt, Jesus Duque-Afonso
Summary: This study retrospectively analyzed the outcomes of 396 patients undergoing autologous hematopoietic stem cell transplantation with BEAM or TEAM conditioning protocols. The results showed that BEAM conditioning was associated with worse survival outcomes in patients with impaired pulmonary function, while PD before transplantation was the only significant factor in patients treated with TEAM.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2023)
Review
Immunology
Robert Zeiser, Olle Ringden, Behnam Sadeghi, Gil Gonen-Yaacovi, Oscar G. Segurado
Summary: Graft versus host disease (GVHD) is a common clinical complication that can occur at any period post allogeneic hematopoietic stem cell transplantation. There is currently no consensus on the management of steroid-refractory acute GVHD and the prognosis for these patients remains poor. Recent advancements in cell therapies, particularly the use of decidua stromal cells (DSCs), have shown promising results in the treatment of acute GVHD.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Gila Mostufi-Zadeh-Haghighi, Pia Veratti, Kyra Zodel, Gabriele Greve, Miguel Waterhouse, Robert Zeiser, Michael L. Cleary, Michael Luebbert, Jesus Duque-Afonso
Summary: This study focused on the characterization of the TGF beta signaling pathway in B-acute lymphoblastic leukemia (ALL) and resistance to the multi-kinase inhibitor dasatinib. The results showed that TGF beta signaling negatively regulates cell growth in B-cell precursor-ALL and in dasatinib-resistant ALL cells. The upregulation of the TGF beta pathway was identified in dasatinib-resistant pre-BCR+/E2A-PBX1(+) ALL cells, and dasatinib partially blocked TGF beta-induced SMAD3 phosphorylation in B-cell precursor ALL cell lines and dasatinib-resistant pre-BCR+/E2A-PBX1(+) ALL cells.
Article
Biochemistry & Molecular Biology
Susan M. Grimes, Heon Seok Kim, Sharmili Roy, Anuja Sathe, Carlos Ayala, Xiangqi Bai, Alison F. Almeda-Notestine, Sarah Haebe, Tanaya Shree, Ronald Levy, Billy T. Lau, Hanlee P. Ji
Summary: In this study, a single-cell method was developed to determine the genotypes of somatic alterations in coding regions of messenger RNAs and integrate these transcript-based variants with their corresponding cell transcriptomes. Nanopore adaptive sampling on single-cell complementary DNA libraries was used to validate coding variants in target gene transcripts, and short-read sequencing was used to characterize the cell types harboring the mutations. CRISPR edits for 16 targets were identified using a cancer cell line, and known variants in the cell line were validated using a 352-gene panel. Variants in primary cancer samples were validated using target gene panels ranging from 161 to 529 genes. A gene rearrangement was also identified in one patient, with the rearrangement occurring in two distinct tumor sites.
Article
Oncology
Miriam Mozaffari Jovein, Gabriele Ihorst, Jesus Duque-Afonso, Ralph Waesch, Hartmut Bertz, Claudia Wehr, Justus Duyster, Robert Zeiser, Juergen Finke, Florian Scherer
Summary: This study evaluated the long-term outcomes of 220 AML patients after primary induction failure (PIF) who underwent allogeneic hematopoietic stem cell transplantation (HCT). The results showed that immediate allogeneic HCT after PIF provides long-term survival and cure in a high-risk population.
BLOOD CANCER JOURNAL
(2023)
Article
Hematology
Omer Jamy, Robert Zeiser, Yi-Bin Chen
Summary: Acute graft-versus-host disease (aGVHD) is a severe complication after allogeneic hematopoietic cell transplant, and the traditional prophylactic and treatment strategies have been reshaped by the approval of new drugs and the emergence of new therapies. Ongoing clinical trials and future goals in this field are discussed, along with the limitations of current trial designs and endpoints.