Article
Oncology
Francesco De Sanctis, Alessia Lamolinara, Federico Boschi, Chiara Musiu, Simone Caligola, Rosalinda Trovato, Alessandra Fiore, Cristina Frusteri, Cristina Anselmi, Ornella Poffe, Tiziana Cestari, Stefania Cane, Silvia Sartoris, Rosalba Giugno, Giulia Del Rosario, Barbara Zappacosta, Francesco Del Pizzo, Matteo Fassan, Erica Dugnani, Lorenzo Piemonti, Emanuela Bottani, Ilaria Decimo, Salvatore Paiella, Roberto Salvia, Rita Teresa Lawlor, Vincenzo Corbo, Youngkyu Park, David A. Tuveson, Claudio Bassi, Aldo Scarpa, Manuela Iezzi, Stefano Ugel, Vincenzo Bronte
Summary: PDAC tumors exhibit strong immunosuppressive characteristics that limit the success of immunotherapy. Research shows that reprogramming the tumor microenvironment by intervening in RNS production can enhance the efficacy of immune-based treatments.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Walther Brochier, Orian Bricard, Pierre G. Coulie
Summary: T cells play a crucial role in the immune response against tumors by recognizing tumor-specific antigens presented by HLA molecules on tumor cells. Immune checkpoint therapy (ICT) can reactivate existing tumor-specific T cells, even without identifying the specific antigens. To minimize the activation of non-tumor-specific T cells, immunizations targeting tumor-specific antigens are considered. However, identifying these antigens is challenging for certain tumors. In this review, we discuss the current understanding of human tumor-specific and tumor-associated antigens and their potential use in cancer immunotherapy.
CLINICAL CANCER RESEARCH
(2023)
Article
Immunology
Qiao Liu, Lisha Wang, Huayu Lin, Zhiming Wang, Jialin Wu, Junyi Guo, Shuqiong Wen, Ling Ran, Zhengliang Yue, Xingxing Su, Qing Wu, Jianfang Tang, Zhirong Li, Li Hu, Lifan Xu, Lilin Ye, Qizhao Huang
Summary: Cytotoxic CD8(+) T cells are the main focus of anti-tumor immunity and immunotherapy research, but transferred tumor-specific CD8(+) T cells have limited effect on suppressing tumor growth. On the other hand, CD4(+) T cells play an important role in curtailing tumor metastasis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Ranran Shi, Yubing Li, Ling Ran, Yu Dong, Xiuman Zhou, Jingwen Tang, Lu Han, Mingshuang Wang, Liwei Pang, Yuanming Qi, Yahong Wu, Yanfeng Gao
Summary: Researchers identified three HLA-A2-restricted neoepitopes that could induce specific antitumor T cell responses in non-MSI-H colorectal cancer, showing promise for potential immunotherapy. The combination of adoptive T cell therapy based on these neoepitopes with immune checkpoint inhibitors, such as anti-PD-1, could provide a promising treatment strategy for non-MSI-H colorectal cancer.
SCIENCE CHINA-LIFE SCIENCES
(2022)
Article
Cell Biology
Karolin I. Wagner, Laura M. Mateyka, Sebastian Jarosch, Vincent Grass, Simone Weber, Kilian Schober, Monika Hammel, Teresa Burrell, Behnam Kalali, Holger Poppert, Henriette Beyer, Sophia Schambeck, Stefan Holdenrieder, Andrea Strotges-Achatz, Verena Haselmann, Michael Neumaier, Johanna Erber, Alina Priller, Sarah Yazici, Hedwig Roggendorf, Marcus Odendahl, Torsten Tonn, Andrea Dick, Klaus Witter, Hrvoje Mijocevic, Ulrike Protzer, Percy A. Knolle, Andreas Pichlmair, Claudia S. Crowell, Markus Gerhard, Elvira D'Ippolito, Dirk H. Busch
Summary: This study isolated TCR repertoires specific for SARS-CoV-2 epitopes restricted to common HLA class I molecules in convalescent individuals. SARS-CoV-2-specific CD8(+) T cells were found to be detectable up to 12 months after infection. The TCR repertoires were diverse, with heterogeneous functional avidity and cytotoxicity towards virus-infected cells.
Article
Oncology
Kai Chen, Yongsu Ma, Xinxin Liu, Xiejian Zhong, Di Long, Xiaodong Tian, Lei Zheng, Yinmo Yang
Summary: This study analyzed the residual lesion of a PDAC patient with high microsatellite instability (MSI-H) using single-cell RNA sequencing. The results showed the presence of a proliferating tumor subcluster, activated pancreatic stellate cells (PSCs), and exhausted T cells in the residual lesion after neoadjuvant treatment with chemotherapy and immunotherapy.
Article
Gastroenterology & Hepatology
Rui Yan, Jianjian Li, Zeru Xiao, Xiaona Fan, Heshu Liu, Ying Xu, Ruya Sun, Jian Liu, Jiannan Yao, Guangyu An, Yan Shi, Yang Ge
Summary: This study found that the gastrointestinal cancer stem cell marker DCLK1 is strongly associated with poor outcomes in colorectal cancer. In vivo experiments confirmed that DCLK1 promotes tumor growth and inhibits the host's antitumor response by recruiting T-cell-suppressive MDSCs. These findings provide a precise therapeutic target for related clinical interventions.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Review
Pharmacology & Pharmacy
Chandra Kishore, Priyanka Bhadra
Summary: 5-Fluorouracil (5-FU) is the first-line chemotherapy drug for colorectal cancer, but patients often develop resistance to it. Immunotherapy has shown promise in treating colorectal cancer, especially in providing long-term remission for some metastatic CRC patients.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Oncology
Jitske van den Bulk, Manon van der Ploeg, Marieke E. Ijsselsteijn, Dina Ruano, Ruud van der Breggen, Rebekka Duhen, Koen C. M. J. Peeters, Arantza Farina-Sarasqueta, Els M. E. Verdegaal, Sjoerd H. van der Burg, Thomas Duhen, Noel F. C. C. de Miranda
Summary: Expression of CD103 and CD39 can specifically identify neoantigen-specific CD8(+) T cells in colorectal cancers (CRCs) with low mutation burden.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Immunology
Vanaja Konduri, Damilola Oyewole-Said, Jonathan Vazquez-Perez, Scott A. Weldon, Matthew M. Halpert, Jonathan M. Levitt, William K. Decker
Summary: NK1.1 and its human homolog CD161 are expressed on various immune cells and play different roles in NK cells, T cells, and NKT cells. CD161-expressing CD8(+) T cells, initially studied in viral infections, have potential implications in tumor immunology, although their exact role is not well understood.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Alex Olvera, Samandhy Cedeno, Anuska Llano, Beatriz Mothe, Jorge Sanchez, Gemma Arsequell, Christian Brander
Summary: Post-translational protein modifications, particularly glycosylation, may impact T cell epitope recognition presented by HLA molecules, but this aspect has been overlooked in HIV research. Studies demonstrated that glycosylation can affect T cell recognition of viral peptides in individuals with chronic HIV infection, indicating the potential importance of glyco-epitope specific T cell immunity in understanding host immune responses against viral infections. New methodologies are needed to accurately assess the role of glycosylation in altering T cell immunity to viral infections.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Ippei Date, Terutsugu Koya, Takuya Sakamoto, Misa Togi, Haruhiko Kawaguchi, Asuka Watanabe, Tomohisa Kato, Shigetaka Shimodaira
Summary: This study demonstrates that human platelet lysate (HPL) can enhance the viability, yield, and purity of interferon-alpha-induced dendritic cells (IFN-DCs), leading to increased antigen-specific cytotoxic T lymphocytes (CTLs) production. Additionally, HPL-induced IFN-DCs show elevated cytokine production and improved endocytic and proteolytic activities, suggesting a novel approach for dendritic cell-based immunotherapies.
Article
Endocrinology & Metabolism
Yan Weng, Lin Wang, Xiao-Yi Wang, Xin-Xiang Fan, Li Yan, Zhi-Hua Li, Shao-Ling Zhang
Summary: This article reports a case of adrenocortical carcinoma (ACC) in which the patient responded well to a combination of mitotane, etoposide, paraplatin (EP-M), and sintilimab. The findings suggest that this treatment option may be promising for patients with similar molecular profiles.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Medicine, Research & Experimental
Neal P. Smith, Bert Ruiter, Yamini V. Virkud, Ang A. Tu, Brinda Monian, James J. Moon, J. Christopher Love, Wayne G. Shreffler
Summary: This study utilized a combination of biological and statistical approaches to define potentially antigen-specific CDR3 repertoires in unselected individuals through FACS of antigen-activated memory CD4(+) T cells and TCR beta sequencing. Application of this method to peanut-allergic individuals identified a library of unique CDR3 beta sequences with similarities to validated antigen-specific repertoires. Further analysis revealed public sequences with high levels of convergent recombination and network analysis showed these sequences to be core with more edges than private counterparts, indicating potential for use in T cell-mediated disorders and biomarker discovery.
Article
Immunology
Antonio J. Martin-Galiano, Francisco Diez-Fuertes, Michael J. McConnell, Daniel Lopez
Summary: The study found that the impact of emerging COVID-19 virus variants on cytotoxic immune protection is not significant, as most of the common HLA class I alleles in the population contain enough epitopes to handle these variants.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemical Research Methods
Greta Forlani, Justine Michaux, HuiSong Pak, Florian Huber, Elodie Lauret Marie Joseph, Elise Ramia, Brian J. Stevenson, Michael Linnebacher, Roberto S. Accolla, Michal Bassani-Sternberg
Summary: The study revealed the diversity of HLA ligandome in GBM cell lines and the significant impact of CIITA expression on HLA-II presentation machinery compared to IFN gamma treatment. It contributes to the identification of novel HLA-I and HLA-II ligands derived from known GBM-associated tumor antigens and suggests that CIITA-expressing GBM cells acquire an antigen presenting cell-like phenotype.
MOLECULAR & CELLULAR PROTEOMICS
(2021)
Article
Oncology
Lili Lu, Yuru Shang, Christina Susanne Mullins, Xianbin Zhang, Michael Linnebacher
Summary: From 2000 to 2016, there was a significant increase in the incidence of pNEN in the US, especially among early-stage patients. While there was improvements in prognosis during 2010-2016, late-stage pNEN patients still had a high risk of death.
Article
Neurosciences
Annett Madadi, Jakob Wolfart, Falko Lange, Hannes Brehme, Michael Linnebacher, Anja U. Braeuer, Andreas Buettner, Thomas Freiman, Christian Henker, Anne Einsle, Simone Rackow, Rudiger Koehling, Timo Kirschstein, Steffen Mueller
Summary: This study found that glioma cells exhibit reduced expression of Kir4.1 channels, leading to impaired K+ buffering which may increase cell excitability and contribute to the epileptogenic nature of gliomas.
NEUROSCIENCE LETTERS
(2021)
Article
Oncology
Carina Arnold, Philipp Demuth, Nina Seiwert, Simon Wittmann, Kerstin Boengler, Birgit Rasenberger, Markus Christmann, Magdalena Huber, Thomas Brunner, Michael Linnebacher, Joerg Fahrer
Summary: Colorectal cancer is a common tumor with increasing incidence and mortality in younger adults. This study identifies devimistat as a promising compound for colorectal cancer therapy, which shows synergistic effects with established antineoplastic drugs in vitro and in vivo.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Cell Biology
Nicole Kiweler, Schwarz Helena, Alexandra Nguyen, Stephanie Matschos, Christina Mullins, Andrea Piee-Staffa, Christina Brachetti, Wynand P. Roos, Guenter Schneider, Michael Linnebacher, Walburgis Brenner, Oliver H. Kraemer
Summary: The expression of HDAC2 in colon cancer cells affects their response to the chemotherapy drug 5-FU and is associated with ATM-mediated sensitivity to 5-FU.
CELL BIOLOGY AND TOXICOLOGY
(2023)
Article
Biology
Falko Lange, Jakob Venus, Daria Shams Esfand Abady, Katrin Porath, Anne Einsle, Tina Sellmann, Valentin Neubert, Gesine Reichart, Michael Linnebacher, Ruediger Koehling, Timo Kirschstein
Summary: In electric fields, glioblastoma cells are capable of galvanotactic migration, and the PI3K/AKT pathway plays a critical role in this process.
Article
Oncology
Ulrike Pfohl, Juergen Loskutov, Sanum Bashir, Ralf Kuhn, Patrick Herter, Markus Templin, Soulafa Mamlouk, Sergei Belanov, Michael Linnebacher, Florian Buertin, Marcus Vetter, Christoph Reinhard, Lena Wedeken, Christian R. A. Regenbrecht
Summary: This research investigated the impact of loss-of-function of the SMAD4 gene on the sensitivity to MEK inhibitors in colorectal cancer using CRISPR technology. It identified a mutation signature related to the TGF-beta/BMP signaling pathway and found a gene signature (SFAB) that can predict sensitivity to MEK inhibitors.
Article
Biochemistry & Molecular Biology
Viktoriya B. Boncheva, Michael Linnebacher, Said Kdimati, Hannah Draper, Laurence Orchard, Ken Mills, Gerald O'Sullivan, Mark Tangney, Barbara-Ann Guinn
Summary: A Crohn's-like lymphoid reaction (CLR) is observed in about 15% of colorectal cancer (CRC) patients and is associated with favourable outcomes. By immunoscreening, the heavy chain of IgG3 (IGHG3) and a novel antigen named UOB-COL-7 were solely recognised by sera from CRC CLR patients. These findings demonstrate the potential of SEREX-identified CRC CLR antigens to act as biomarkers for CRC.
Article
Biochemistry & Molecular Biology
Randy Przybylla, Christina Susanne Mullins, Mathias Krohn, Stefan Oswald, Michael Linnebacher
Summary: This study established a platform of colorectal cancer patient-derived cell lines for evaluation of human intestinal drug absorption and metabolism, which could be superior tools for predicting oral drug absorption and intestinal drug-drug interactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Julia Hoernschemeyer, Timo Kirschstein, Gesine Reichart, Christin Sasse, Jakob Venus, Anne Einsle, Katrin Porath, Michael Linnebacher, Ruediger Koehling, Falko Lange
Summary: Glioblastoma is a common and aggressive primary brain tumor with multiple genetic and epigenetic alterations. Small-molecule kinase inhibitors regorafenib and MK-2206, as well as dactolisib, showed effective results in all preclinical tumor models, while trametinib was found to be highly resistant.
Article
Oncology
Su Zhaoran, Christina Susanne Linnebacher, Michael Linnebacher
Summary: This study is the first to describe the significantly upregulated expression of the SEC23A gene in stomach adenocarcinoma (STAD). It also identified an association with disease progression, patients' prognosis, and infiltrating immune cell types and their activity. SEC23A is proposed as an independent prognostic factor with a putative role in immune response regulation in STAD.
Article
Oncology
Ramy Ashry, Al-Hassan M. Mustafa, Kristin Hausmann, Michael Linnebacher, Susanne Strand, Wolfgang Sippl, Matthias Wirth, Oliver H. Kraemer
Summary: Tumors in the pancreas and colon are still a clinical challenge. Different gene expression profiles between cancer cells and normal cells can be targeted by drugs that modulate protein acetylation. KH16 is a novel compound that induces hyperacetylation, leading to cell death in tumor cells while sparing normal cells. It shows superior efficacy compared to clinically established drugs. Further studies can focus on KH16 and similar compounds for cancer therapy.
Article
Cell Biology
Randy Przybylla, Mathias Krohn, Marie-Luise Sellin, Marcus Frank, Stefan Oswald, Michael Linnebacher
Summary: The commonly used in vitro model for ADME purposes, the Caco-2 cell line, has limitations in predicting intestinal drug absorption due to differences in gene and protein expression. This study evaluated low-passaged patient-derived colorectal cancer cell lines and found three lines with higher similarity to jejunal epithelial tissue cells and higher regulatory potential of drug transporters compared to the Caco-2 model.
Article
Biology
Falko Lange, Katrin Porath, Tina Sellmann, Anne Einsle, Robert Jaster, Michael Linnebacher, Ruediger Koehling, Timo Kirschstein
Summary: Migration of colorectal cancer cells greatly contributes to the progression of the disease. Direct-current electrical fields, known as galvanotaxis, could be a driving factor for directional migration. In this study, we investigated the migration of colorectal cancer cells in electrical fields and found that three out of five cell lines exhibited preferred cathodal migration. We determined that voltage-gated calcium channels and intracellular signaling pathways such as MEK and AKT played important roles in galvanotaxis.
Article
Biochemistry & Molecular Biology
Sandra Schwarz, Michael Linnebacher
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
