Review
Biochemistry & Molecular Biology
Imke Atreya, Markus F. Neurath
Summary: The successful treatment of advanced colorectal cancer remains a challenge due to low immunogenicity. Enhancing the accumulation of cytolytic effector T lymphocytes and other cellular mediators is targeted for improved outcomes. Studying the molecular mechanisms and cellular interactions in the tumor microenvironment is crucial for identifying new therapeutic targets.
Article
Oncology
Maarit Ahtiainen, Hanna Elomaa, Juha P. Vayrynen, Erkki-Ville Wirta, Teijo Kuopio, Olli Helminen, Toni T. Seppala, Ilmo Kellokumpu, Jukka-Pekka Mecklin
Summary: Metastasis is the main cause of cancer mortality, with the liver and lungs being the most common sites for colorectal cancer (CRC) metastases. High immune cell infiltration and PD-L1 positivity were found to almost double in metastases compared to primary tumors, and high ICS in the least immune-infiltrated metastases of pMMR CRC patients was confirmed to have prognostic value. The differences in immune contexture between primary tumors and metastases may have implications for treatment strategies for advanced CRC patients.
Article
Gastroenterology & Hepatology
Alessia Potenza, Chiara Balestrieri, Martina Spiga, Luca Albarello, Federica Pedica, Francesco Manfredi, Beatrice Claudia Cianciotti, Claudia De Lalla, Oronza A. Botrugno, Cristina Faccani, Lorena Stasi, Elena Tassi, Silvia Bonfiglio, Giulia Maria Scotti, Miriam Redegalli, Donatella Biancolini, Barbara Camisa, Elena Tiziano, Camilla Sirini, Monica Casucci, Chiara Iozzi, Danilo Abbati, Fabio Simeoni, Dejan Lazarevic, Ugo Elmore, Guido Fiorentini, Giulia Di Lullo, Giulia Casorati, Claudio Doglioni, Giovanni Tonon, Paolo Dellabona, Riccardo Rosati, Luca Aldrighetti, Eliana Ruggiero, Chiara Bonini
Summary: This study described the functional phenotype of T cells in primary and metastatic colorectal cancers using high-dimensional flow cytometry, RNA sequencing, and immunohistochemistry. It also developed CRC-specific engineered T cells using lentiviral vectors and CRISPR/Cas9 genome editing technologies.
Review
Biochemistry & Molecular Biology
Monika Zajkowska, Barbara Mroczko
Summary: The liver plays crucial functions in the human body, but it is susceptible to damage from various factors, leading to liver diseases such as primary liver cancer. Chemokines have been found to play a significant role in the development of liver cancer, making them useful in detecting and monitoring the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Costanza Ballaro, Valeria Quaranta, Gianluigi Giannelli
Summary: Colorectal cancer is a common malignancy with a high mortality rate, mainly caused by colorectal liver metastasis. Communication between cancer cells and the environment plays a crucial role in creating a favorable tumor microenvironment, and this communication is mediated by soluble molecules such as cytokines. This review highlights the involvement of various cytokines in the development of colorectal liver metastases and emphasizes the complex nature of the cytokine milieu and its therapeutic implications.
Review
Biochemistry & Molecular Biology
Daniel-Clement Osei-Bordom, Sivesh Kamarajah, Niki Christou
Summary: In the clinical management of liver metastasis of colorectal cancer, surgeons and oncologists categorize the metastasis into resectable and non-resectable groups to initiate tailored therapeutics. The combination of targeted therapies and biotherapies around these two entities is being actively explored to determine the ideal conditions for their application to improve patient survival and quality of life.
Article
Oncology
Chong Zhang, Xiang-Yu Wang, Jie-Liang Zuo, Xue-Fu Wang, Xiao-Wen Feng, Bo Zhang, Yi-Tong Li, Chen-He Yi, Peng Zhang, Xiao-Chen Ma, Zhen-Mei Chen, Yue Ma, Jia-Hao Han, Bao-Rui Tao, Rui Zhang, Tian-Qi Wang, Li Tong, Wang Gu, Si-Yu Wang, Xiao-Fei Zheng, Wen-Kang Yuan, Zi-Jie Kan, Jie Fan, Xiang-Yang Hu, Jun Li, Chao Zhang, Jin-Hong Chen
Summary: Tertiary lymphoid structures (TLSs) in colorectal cancer liver metastases (CRCLM) are found to be associated with prognosis. The study analyzed data from 603 CRCLM patients and found that higher intratumor TLSs score is correlated with better prognosis, while higher peritumor TLSs score is correlated with poorer survival. Additionally, the study also found a correlation between immune cell composition within TLSs and TLSs score.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Immunology
Julien Viot, Syrine Abdeljaoued, Angelique Vienot, Evan Seffar, Laurie Spehner, Adeline Bouard, Kamal Asgarov, Jean-Rene Pallandre, Elodie Renaude, Elodie Klajer, Chloe Molimard, Franck Monnien, Frederic Bibeau, Celia Turco, Bruno Heyd, Paul Peixoto, Eric Hervouet, Romain Loyon, Alexandre Doussot, Christophe Borg, Marie Kroemer
Summary: This study assessed the prognostic value of CD226 in tumor-infiltrating lymphocytes (TILs) derived from colorectal cancer (CRC) liver metastases. The results showed that CD226 expression on CD8(+) T cells is associated with the immune context and has independent prognostic value in CRC liver metastases.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Gastroenterology & Hepatology
Kevin M. Sullivan, Xiuyun Jiang, Prajna Guha, Christopher Lausted, Jason A. Carter, Cynthia Hsu, Kevin P. Labadie, Karan Kohli, Heidi L. Kenerson, Sara K. Daniel, Xiaowei Yan, Changting Meng, Arezou Abbasi, Marina Chan, Y. David Seo, James O. Park, Ian Nicholas Crispe, Raymond S. Yeung, Teresa S. Kim, Taranjit S. Gujral, Qiang Tang, Steven C. Katz, Venu G. Pillarisetty
Summary: Neutralizing the effects of IL-10 in human CRLM has shown to enhance T-cell-mediated carcinoma cell death, increase the proportion of CD8(+) T cells, and increase the HLA-DR expression of macrophages. Blocking IL-10 signaling also rescues CAR-T cell function from myeloid cell-mediated immunosuppression and augments CEA-specific CAR-T cell activation and cytotoxicity.
Article
Multidisciplinary Sciences
William W. Ho, Igor L. Gomes-Santos, Shuichi Aoki, Meenal Datta, Kosuke Kawaguchi, Nilesh P. Talele, Sylvie Roberge, Jun Ren, Hao Liu, Ivy X. Chen, Patrik Andersson, Sampurna Chatterjee, Ashwin S. Kumar, Zohreh Amoozgar, Qixian Zhang, Peigen Huang, Mei Rosa Ng, Vikash P. Chauhan, Lei Xu, Dan G. Duda, Jeffrey W. Clark, Mikael J. Pittet, Dai Fukumura, Rakesh K. Jain
Summary: Liver metastasis of mismatch repair-proficient (pMMR) CRCs is unresponsive to immune checkpoint blockade (ICB) therapy, while the same tumors are sensitive to ICB therapy when grown subcutaneously. Dendritic cells play a crucial role in increasing the efficacy of immuno-therapies against pMMR CRC liver metastases, as evidenced by increased infiltration and improved survival in mouse models. Compared to subcutaneous tumors, orthotopic liver metastases of pMMR CRCs show a paucity of activated T cells and dendritic cells, indicating the importance of utilizing orthotopic tumor models in guiding human clinical trials.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, Research & Experimental
Yangsong He, Yanan Han, A-Hui Fan, Danxiu Li, Boda Wang, Kun Ji, Xin Wang, Xiaodi Zhao, Yuanyuan Lu
Summary: This study compares the expression profile of immune cells in liver metastases and primary tumors in colorectal cancer patients. The researchers found differences in the spatial distribution of immune cells between these two types of tumors, with more immunosuppressive cells present in liver metastases, particularly macrophages with a CD68(-)CD163(+) phenotype.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Review
Cell Biology
Lavanya Goodla, Xiang Xue
Summary: This brief review discusses the involvement of three representative cytokines (TNF-alpha, IL-6 and IL-1 beta), a lipid molecule PGE2 and two chemokines (CXCL1 and CXCL2) in the process of CRC liver metastases.
Article
Surgery
Jenna N. Whitrock, Stephen J. Hartman, Shimul A. Shah
Summary: In patients with unresectable liver metastases from colorectal cancer, chemotherapy alone is associated with significant mortality. Liver transplant is emerging as a promising treatment alternative for appropriately selected patients. Several key clinical trials, including SECA-I and SECA-II, have demonstrated promising survival outcomes, and further trials are ongoing to evaluate the safety of this approach.
Review
Biochemistry & Molecular Biology
Carolin Czauderna, Kim Luley, Nikolas von Bubnoff, Jens U. Marquardt
Summary: Liver metastases are the most common site of metastasis in colorectal cancer. Current treatment approaches involve systemic therapies and surgical/interventional strategies, with the use of predictive and prognostic biomarkers leading to improved survival rates. Treatment selection based on patient status, tumor characteristics, and molecular/genetic status is recommended for better outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Physiology
H. L. Notbohm, F. Moser, J. Goh, J. F. Feuerbacher, W. Bloch, M. Schumann
Summary: The immune system's role in exercise responses and adaptations is important, but the impact of fluctuating hormone concentrations across the menstrual cycle on these processes is unknown. This systematic review with meta-analysis compared immune and inflammatory parameters between menstrual cycle phases. The findings suggest that certain parameters of innate immunity, such as leukocytes, monocytes, granulocytes, neutrophils, and leptin concentrations, are higher in the luteal phase compared to the follicular phase at rest. The exercise-induced response of these parameters also indicate a higher pro-inflammatory response in the luteal phase. However, more research is needed to understand the exercise responses in different hormonal profiles.
Article
Multidisciplinary Sciences
Maria Xydia, Raheleh Rahbari, Eliana Ruggiero, Iain Macaulay, Maxime Tarabichi, Robert Lohmayer, Stefan Wilkening, Tillmann Michels, Daniel Brown, Sebastiaan Vanuytven, Svetlana Mastitskaya, Sean Laidlaw, Niels Grabe, Maria Pritsch, Raffaele Fronza, Klaus Hexel, Steffen Schmitt, Michael Mueller-Steinhardt, Niels Halama, Christoph Domschke, Manfred Schmidt, Christof von Kalle, Florian Schuetz, Thierry Voet, Philipp Beckhove
Summary: Regulatory T cells in breast cancer do not show clonal relationship with their circulating counterpart, but share a common origin with intratumoral antigen-experienced conventional T cells.
NATURE COMMUNICATIONS
(2021)
Article
Nutrition & Dietetics
Daniel Boakye, Lina Jansen, Ben Schoettker, Eugene H. J. M. Jansen, Niels Halama, Haifa Maalmi, Xin Gao, Jenny Chang-Claude, Michael Hoffmeister, Hermann Brenner
Summary: The study found a correlation between 25(OH)D and total thiol concentration in colorectal cancer patients, with the relationship between 25(OH)D and patient prognosis depending on antioxidant capacity levels. The survival advantage of adequate vitamin D in CRC patients is most pronounced among those with low antioxidant capacity.
AMERICAN JOURNAL OF CLINICAL NUTRITION
(2021)
Article
Oncology
Fee Klupp, Malte Sass, Frank Bergmann, Elias Khajeh, Omid Ghamarnejad, Matthias Hassenpflug, Arianeb Mehrabi, Yakup Kulu
Summary: The study investigated the association between the expression of EGFRs and their ligands in tumors with response to cetuximab therapy in mCRC patients. However, the results showed that there was no significant correlation between the expression levels of EGFRs and their ligands with the treatment response. Therefore, EGFR or EGFR ligand expression does not predict treatment response in CRC patients with liver metastases following cetuximab therapy.
Article
Biochemistry & Molecular Biology
Fee Klupp, Christoph Kahlert, Clemens Franz, Niels Halama, Nikolai Schleussner, Naita M. Wirsik, Arne Warth, Thomas Schmidt, Alexis B. Ulrich
Summary: Granulin is overexpressed in colorectal cancer patients and is significantly associated with impaired overall survival, indicating its potential as a prognostic biomarker. Downregulation of Granulin by siRNA can significantly reduce the invasive capabilities of HCT-116 cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Azaz Ahmed, Sophia Koehler, Rosa Klotz, Nathalia Giese, Thilo Hackert, Christoph Springfeld, Inka Zoernig, Dirk Jaeger, Niels Halama
Summary: Pancreatic ductal adenocarcinoma (PDA) patients with tertiary lymphoid structures (TLS) have better prognosis. TLS-positive tissues show higher density of CD8(+) T cells and CD20(+) B cells, as well as higher levels of IL2 in the peritumoral stroma. Serum IL2 levels may serve as a potential marker for TLS prediction.
Article
Biology
Christopher J. Neufeldt, Berati Cerikan, Mirko Cortese, Jamie Frankish, Ji-Young Lee, Agnieszka Plociennikowska, Florian Heigwer, Vibhu Prasad, Sebastian Joecks, Sandy S. Burkart, David Y. Zander, Baskaran Subramanian, Rayomand Gimi, Seetharamaiyer Padmanabhan, Radhakrishnan Iyer, Mathieu Gendarme, Bachir El Debs, Niels Halama, Uta Merle, Michael Boutros, Marco Binder, Ralf Bartenschlager
Summary: SARS-CoV-2 infection can lead to severe symptoms and long-lasting lung damage or death. This is often associated with high levels of pro-inflammatory cytokines and low antiviral responses. A specific activation of NF-kappa B and block of IRF3 nuclear translocation were observed in infected cells. The inflammatory response is mediated by cGAS-STING activation and can be attenuated through STING-targeting drugs.
COMMUNICATIONS BIOLOGY
(2022)
Article
Oncology
Georg Martin Haag, Christoph Springfeld, Barbara Gruen, Leonidas Apostolidis, Stefanie Zschaebitz, Mareike Dietrich, Anne-Katrin Berger, Tim Frederik Weber, Inka Zoernig, Marina Schaaf, Lisa Waberer, Daniel Wilhelm Muller, Salah-Eddin Al-Batran, Niels Halama, Dirk Jaeger
Summary: This study investigated the safety and efficacy of pembrolizumab and maraviroc in refractory colorectal cancer. The results showed that this treatment was feasible with low toxicity, but had limited clinical activity in mismatch repair proficient colorectal cancer patients.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Kuailu Lin, Franziska Baenke, Xixi Lai, Martin Schneider, Dominic Helm, Heike Polster, Venkatesh S. Rao, Nicole Ganig, Fang Cheng Wong, Lena Seifert, Adrian M. Seifert, Beatrix Jahnke, Nicole Kretschmann, Tjalf Ziemssen, Fee Klupp, Thomas Schmidt, Martin Schneider, Yi Han, Tim F. Weber, Verena Plodeck, Heiner Nebelung, Nathalie Schmitt, Felix Korell, Bruno C. Koehler, Carina Riediger, Juergen Weitz, Nuh N. Rahbari, Christoph Kahlert
Article
Multidisciplinary Sciences
Thomas Walle, Joscha A. Kraske, Boyu Liao, Benedicte Lenoir, Carmen Timke, Emilia von Bohlen Und Halbach, Florian Tran, Paul Griebel, Dorothee Albrecht, Azaz Ahmed, Meggy Suarez-Carmona, Alejandro Jimenez-Sanchez, Tizian Beikert, Alexandra Tietz-Dahlfuss, Ayse Nur Menevse, Gabriele Schmidt, Manuela Brom, Jens H. W. Pahl, Wiebke Antonopoulos, Matthias Miller, Ramon Lopez Perez, Felix Bestvater, Nathalia A. Giese, Philipp Beckhove, Philip Rosenstiel, Dirk Jaeger, Oliver Strobel, Dana Pe'er, Niels Halama, Juergen Debus, Adelheid Cerwenka, Peter E. Huber
Summary: NK cells play a central role in the radiation-induced immune response, enhancing tumor control through the secretion of CXCL8/IL-8 and recruiting immune cells. This discovery suggests a rational cancer treatment strategy combining NK cells with radiotherapy.
Article
Oncology
Xin-Wen Zhang, Alexander Wald, Martin Salzmann, Niels Halama, Jessica C. Hassel
Summary: Paraneoplastic leukemoid reaction (PLR) is a rare phenomenon associated with poor prognosis and rapid disease progression in metastasized melanoma. This study analyzed the cytokine concentrations in patients' serum samples during PLR and performed immunohistochemical staining on tumor tissue. The results showed a correlation between tumor burden and neutrophilia, as well as an increase in proinflammatory cytokines, proangiogenic cytokines, and immune stem cell growth factors during PLR. These findings provide a basis for further functional analysis and targeted therapeutic approaches against PLR.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Immunology
Azaz Ahmed, Rosa Klotz, Sophia Koehler, Nathalia Giese, Thilo Hackert, Christoph Springfeld, Dirk Jaeger, Niels Halama
Summary: This study investigated the immune features of the stroma in PDA patients, revealing a significant association of IL9 and IL18 with patient survival outcomes. IL9 was linked to an anti-tumoral cytokine network, while IL18 was associated with exhausted T cells. Patients with PDA showed higher serum levels of IL9 and lower levels of IL18 compared to healthy controls.
FRONTIERS IN IMMUNOLOGY
(2022)
Letter
Medicine, General & Internal
Juri Fuchs, Anastasia Murtha-Lemekhova, Jan Pfeiffenberger, Alexander Fichtner, Patrick Guenther, Niels Halama, Philipp Mayer, Daniel Hornuss, Rosa Klotz, Pascal Probst, Katrin Hoffmann
Summary: This article introduces a multidisciplinary project aiming to establish evidence-based therapies for rare liver diseases. They will use systematic reviews and meta-analyses, combined with case reports and small patient series, to develop guidelines for rare liver conditions affecting pediatric and adult populations.
SYSTEMATIC REVIEWS
(2022)
Correction
Oncology
Thomas Walle, Sunanjay Bajaj, Joscha A. Kraske, Thomas Rosner, Christiane S. Cussigh, Katharina A. Kalber, Lisa Jasmin Muller, Sophia Boyoung Strobel, Jana Burghaus, Stefan M. Kallenberger, Christoph K. Stein-Thoringer, Maximilian Jenzer, Antonia Schubert, Steffen Kahle, Anja Williams, Birgit Hoyler, Lin Zielske, Renate Skatula, Stefanie Sawall, Mathias F. Leber, Russell Z. Kunes, Johannes Krisam, Carlo Fremd, Andreas Schneeweiss, Jurgen Krauss, Leonidas Apostolidis, Anne Katrin Berger, Georg M. Haag, Stefanie Zschabitz, Niels Halama, Christoph Springfeld, Romy Kirsten, Jessica C. Hassel, Dirk Jager, Guy Ungerechts
Article
Oncology
Thomas Walle, Sunanjay Bajaj, Joscha A. Kraske, Thomas Roesner, Christiane S. Cussigh, Katharina A. Kaelber, Lisa Jasmin Mueller, Sophia Boyoung Strobel, Jana Burghaus, Stefan Kallenberger, Christoph Stein-Thoeringer, Maximilian Jenzer, Antonia Schubert, Steffen Kahle, Anja Williams, Birgit Hoyler, Lin Zielske, Renate Skatula, Stefanie Sawall, Mathias F. Leber, Russell Z. Kunes, Johannes Krisam, Carlo Fremd, Andreas Schneeweiss, Juergen Krauss, Leonidas Apostolidis, Anne Katrin Berger, Georg M. Haag, Stefanie Zschaebitz, Niels Halama, Christoph Springfeld, Romy Kirsten, Jessica C. Hassel, Dirk Jaeger, Guy Ungerechts, Stefan M. Kallenberger, Christoph K. Stein-Thoeringer, Omar Abdelrahim, Elena Busch, Patrick Derigs, Katharina Dischinger, Fouad Mitri, Kerstin Schmidt, Irfan A. Bhatti, Barbara Gruen, Nicolas Hohmann, Lena Woydack, Xin-Wen Zhang, Dyke Ferber, Andreas Mock, Tillmann Pompecki, Timo Schank, Jurgen Krauss
Summary: Walle & Bajaj et al. analyzed the occurrence of cytokine release syndrome (CRS) in cancer patients receiving immune-checkpoint inhibitors (ICIs) after COVID-19 vaccination. They found that although elevated cytokines levels were common, they did not result in detectable CRS symptoms.
Article
Clinical Neurology
Maria T. Panayotacopoulou, Ismini Papageorgiou, Marianna Pagida, Alexandra E. Katsogridaki, Margarita Chrysanthou-Piterou, Nektarios A. Valous, Niels Halama, Efstratios Patsouris, Anastasia E. Konstantinidou
Summary: Perinatal hypoxia-ischemia can lead to a significant reduction of tyrosine hydroxylase in dopaminergic neurons of neonates, while microglia activation may occur before neuronal death. The expression and morphology of microglia can be affected by the severity and duration of perinatal hypoxia-ischemia, which may predispose neonates to neuropsychiatric disorders later in life.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2022)