Review
Immunology
Ali Razaghi, Mickael Durand-Dubief, Nele Brusselaers, Mikael Bjornstedt
Summary: PD-1 and PD-L1 play crucial roles in immune regulation and can be targeted for cancer treatment. Blocking PD-1/PD-L1 can enhance tumor recognition by activated T cells and combining it with type I interferon (IFN) can further improve therapeutic efficacy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Lingyi Fu, Sen Li, WeiWei Xiao, Kuai Yu, Shuo Li, Sujing Yuan, Jianfei Shen, Xingjun Dong, Ziqian Fang, Jianeng Zhang, Siyu Chen, Wende Li, Hua You, Xiaojun Xia, Tiebang Kang, Jing Tan, Gong Chen, An-Kui Yang, YuanHong Gao, Penghui Zhou
Summary: The study demonstrated that Dgka mediates T-cell dysfunction during anti-PD-1 therapy. Inhibiting Dgka can delay T-cell exhaustion and enhance the efficacy of anti-PD-1 therapy. Additionally, the expression of DGKA in cancer cells promotes tumor growth via the AKT signaling pathway.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Cell Biology
Weixin Chen, Jia Ming Nickolas Teo, Siu Wah Yau, Melody Yee -Man Wong, Chun-Nam Lok, Chi-Ming Che, Asif Javed, Yuanhua Huang, Stephanie Ma, Guang Sheng Ling
Summary: This study reveals that type I interferons (IFN-Is) enhance the exhaustion of CD8+ T cells in tumors, resulting in poor response to immune checkpoint blockade therapy. CD8+ T cells without IFN-I signaling show less exhaustion features and have a stronger response to immune checkpoint blockade therapy. Mechanistically, chronic IFN-I stimulation disrupts lipid metabolism and redox balance, promoting lipid peroxidation and metabolic and functional exhaustion of CD8+ T cells.
Article
Dentistry, Oral Surgery & Medicine
So Mi Jeon, Je Sun Lim, Su Hwan Park, Hyung Joon Kim, Hyung-Ryong Kim, Jong-Ho Lee
Summary: PD-L1 and PD-1 signaling negatively regulate the osteo-/odontogenic differentiation of hDPSCs. Blocking PD-1 signaling enhances osteo-/odontogenic differentiation of hDPSCs, suggesting it as a potential therapeutic strategy.
INTERNATIONAL JOURNAL OF ORAL SCIENCE
(2022)
Article
Oncology
Luiza Martins Nascentes Melo, Dayana Herrera-Rios, Daniel Hinze, Stefanie Loeffek, Irem Oezel, Roberta Turiello, Juliane Klein, Sonia Leonardelli, Isa-Vanessa Westedt, Yahya Al-Matary, Sara Egea-Rodriguez, Alexandra Brenzel, Maja Bau, Antje Sucker, Eva Hadaschik, Florian Wirsdoerfer, Helmut Hanenberg, Niklas Uhlenbrock, Daniel Rauh, Joanna Pozniak, Florian Rambow, Jean-Christophe Marine, Maike Effern, Nicole Glodde, Dirk Schadendorf, Jadwiga Jablonska, Michael Hoelzel, Iris Helfrich
Summary: This study identified HSD11B1 as a negative feedback mechanism that limits the efficacy of PD-1 blockade, and showed that HSD11B1 inhibitors can enhance the effectiveness of immunotherapy for melanoma. Additionally, high levels of HSD11B1 were associated with poor responses to immune checkpoint inhibitors in patients with advanced melanoma.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Multidisciplinary Sciences
Nitin Roper, Moises J. Velez, Alberto Chiappori, Yoo Sun Kim, Jun S. Wei, Sivasish Sindiri, Nobuyuki Takahashi, Deborah Mulford, Suresh Kumar, Kris Ylaya, Christopher Trindade, Irena Manukyan, Anna-Leigh Brown, Jane B. Trepel, Jung-Min Lee, Stephen Hewitt, Javed Khan, Anish Thomas
Summary: This study identifies elevated Notch signaling as a significant predictor of clinical benefit in immune checkpoint blockade (ICB) for relapsed small cell lung cancer (SCLC) patients. Activation of Notch signaling induces a low NE phenotype, leading to increased expression of antigen processing and presentation machinery (APM) genes and improved intrinsic tumor immunity.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
John D. Klement, Priscilla S. Redd, Chunwan Lu, Alyssa D. Merting, Dakota B. Poschel, Dafeng Yang, Natasha M. Savage, Gang Zhou, David H. Munn, Padraic G. Fallon, Kebin Liu
Summary: This study found that tumor cell surface PD-L1 does not suppress cytotoxic T lymphocyte activity and has no effect on primary tumor growth. However, deletion of tumor cell surface PD-L1 decreases lung metastasis in a CTL-dependent manner. Depletion of myeloid cells or knocking out PD-1 in myeloid cells impairs PD-L1 promotion of tumor lung metastasis. Single-cell RNA sequencing revealed that PD-L1 engages myeloid cells PD-1 to activate SHP2 and repress the IFN-I-STAT1-CXCL9 pathway to impair CTL recruitment in lung metastasis.
Article
Medicine, Research & Experimental
Lucas A. Horn, Paul L. Chariou, Sofia R. Gameiro, Haiyan Qin, Masafumi Iida, Kristen Fousek, Thomas J. Meyer, Margaret Cam, Dallas Flies, Solomon Langermann, Jeffrey Schlom, Claudia Palena
Summary: Collagens in the ECM play dual roles in tumor immune infiltration by acting as a physical barrier and ligand for immune inhibitory receptors. TGF-beta contributes to ECM shaping by stimulating collagen production and remodeling. Targeting ECM components along with immune checkpoint blockade therapy shows promising results in achieving high cure rates and long-term tumor-specific protection.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Oncology
Yu Yuan, Abdalla Adam, Chen Zhao, Honglei Chen
Summary: Immune checkpoint blockade targeting PD-1/PD-L1 has shown promising therapeutic efficacy in various tumors, but resistance can hinder its effectiveness. This review examines the role of PD-L1 in therapy resistance, particularly through the PD-1/PD-L1 pathway, and highlights potential combination therapies to overcome this resistance.
Review
Pharmacology & Pharmacy
Zikun Peng, Ming Li, Huayi Li, Qinglei Gao
Summary: Immune checkpoint inhibitors (ICIs) have revolutionized treatment in oncology, but have shown modest efficacy in ovarian cancer. This review summarizes clinical trials of PD-1/PD-L1 blockade in ovarian cancer, categorizes resistance mechanisms, and introduces candidate approaches to enhance the efficacy of anti-PD-1/PD-L1 antibodies by rewiring the tumor microenvironment (TME).
DRUG DISCOVERY TODAY
(2023)
Article
Oncology
Qingsheng Li, Phuong T. Ngo, Nejat K. Egilmez
Summary: The study demonstrates that resistance to anti-PD-1 treatment in murine lung cancer models may be due to an increase in IL-17 production, which desensitizes CD8(+) T-cells to therapy. Conversely, neutralizing IL-17 can enhance CD8(+) T-cell activity and reduce tumor burden. Activation of CD8(+) T-cells is crucial for tumor eradication in therapy, and the ratio of CD8(+)/RORc(+) cells in pre-therapy tumor biopsy samples correlates with response to immune checkpoint blockade in NSCLC patients.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Oncology
Weijian Wu, Huiying Xu, Chenyang Liao, Youqiao Wang, Ruirui Wu, Jiaxin Wu, Wenlv Zheng, Yunzhi Li, Chaoying Jin, Yuxuan Zhao, Junmin Quan, Xin Yue, Xianzhang Bu
Summary: This study reveals that USP14 is one of the major suppressors of IFN production and impairs the activation of IRF3. Blockade of USP14 enhances STING signaling activation and promotes radiation-induced adaptive immune responses.
Review
Oncology
Tian Tian, Zhaoming Li
Summary: Blocking therapy targeting programmed death receptor 1 (PD-1) or programmed death ligand 1 (PD-L1) has revolutionized the treatment of malignant tumors, but patient response rates are low and drug resistance is a major concern. Combining this therapy with Tim-3 blockade may offer a promising approach to overcoming resistance in cancer immunotherapy.
FRONTIERS IN ONCOLOGY
(2021)
Review
Immunology
Karima Landelouci, Shruti Sinha, Genevieve Pepin
Summary: Fanconi Anemia (FA) is a genome instability syndrome caused by mutations in repair genes, leading to congenital abnormalities, premature aging, and bone marrow failure. There is a close relationship between genome instability, inflammation, and the production of type-I Interferon. Understanding the molecular mechanisms of type-I Interferon activation in FA may lead to the discovery of therapeutic targets for the associated inflammation and premature aging.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Oncology
Steven B. Maron, Walid Chatila, Henry Walch, Joanne F. Chou, Nicholas Ceglia, Ryan Ptashkin, Richard Kinh Gian Do, Viktoriya Paroder, Neeta Pandit-Taskar, Jason S. Lewis, Tiago Biachi De Castria, Shalom Sabwa, Fiona Socolow, Lara Feder, Jasmine Thomas, Isabell Schulze, Kwanghee Kim, Arijh Elzein, Viktoria Bojilova, Matthew Zatzman, Umesh Bhanot, Rebecca J. Nagy, Jeeyun Lee, Marc Simmons, Michal Segal, Geoffrey Yuyat Ku, David H. Ilson, Marinela Capanu, Jaclyn F. Hechtman, Taha Merghoub, Sohrab Shah, Nikolaus Schultz, David B. Solit, Yelena Y. Janjigian
Summary: The study highlights the clinical significance of identifying baseline intrapatient heterogeneity and serial ctDNA monitoring in HER2-positive esophagogastric cancer patients. These factors can be used to identify early evidence of treatment resistance, guiding proactive therapy escalation or deescalation.
CLINICAL CANCER RESEARCH
(2023)
Review
Oncology
Amir Ajoolabady, Daolin Tang, Guido Kroemer, Jun Ren
Summary: Hepatocellular carcinoma is a prevalent form of liver cancer, with genetic, environmental, and behavioral factors influencing its development. Ferroptosis, a form of nonapoptotic cell death, has potential for suppressing hepatocellular carcinoma. However, malignant cells can develop mechanisms to resist ferroptosis.
BRITISH JOURNAL OF CANCER
(2023)
Review
Biochemistry & Molecular Biology
Carlos Lopez-Otin, Maria A. Blasco, Linda Partridge, Manuel Serrano, Guido Kroemer
Summary: Aging is driven by hallmarks that manifest with age, accelerate aging when accentuated experimentally, and can be decelerated, stopped, or reversed with therapeutic interventions. The twelve proposed hallmarks of aging include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. These hallmarks are interconnected with each other and with the recently proposed hallmarks of health.
Review
Cell Biology
Carlos Lopez-Otin, Federico Pietrocola, David Roiz-Valle, Lorenzo Galluzzi, Guido Kroemer
Summary: Both aging and cancer share similar characteristics, known as hallmarks, some of which are common metahallmarks. While some aging hallmarks suppress cancer development, others have context-dependent effects. The relationship between aging-associated nutrient-sensing and cancer-related cellular metabolism alterations is complex. Understanding the interplay between aging and cancer has significant implications for cancer morbidity and mortality in the elderly and for therapeutic strategies.
Article
Cell Biology
Maria Castedo, Antoine Lafarge, Guido Kroemer
Summary: Deletion or inhibition of the PARP1 gene protects mice against cerebral ischemia and Parkinson's disease, while PARP1 inhibitors are used to eradicate vulnerable cancer cells. Excessive activation of PARP1 is involved in a specific cell death pathway called parthanatos, and inhibition of PARP1 in cancer cells amplifies DNA damage to a lethal level. Therefore, PARP1 plays a context-dependent role in cell fate decisions. Additionally, PARP1 appears to have an ambiguous role in organismal aging.
Article
Multidisciplinary Sciences
Stephanie Solier, Sebastian Mueller, Tatiana Caneque, Antoine Versini, Arnaud Mansart, Fabien Sindikubwabo, Leeroy Baron, Laila Emam, Pierre Gestraud, G. Dan Pantos, Vincent Gandon, Christine Gaillet, Ting-Di Wu, Florent Dingli, Damarys Loew, Sylvain Baulande, Sylvere Durand, Valentin Sencio, Cyril Robil, Francois Trottein, David Pericat, Emmanuelle Naeser, Celine Cougoule, Etienne Meunier, Anne-Laure Begue, Helene Salmon, Nicolas Manel, Alain Puisieux, Sarah Watson, Mark A. Dawson, Nicolas Servant, Guido Kroemer, Djillali Annane, Raphael Rodriguez
Summary: Inflammation is a complex physiological process that involves immune cells clearing sources of injury. Excessive inflammation is associated with infection and several diseases. The cell surface glycoprotein CD44 mediates the uptake of metals, including copper, and affects the metabolic and epigenetic states involved in inflammation.
Review
Cardiac & Cardiovascular Systems
Mahmoud Abdellatif, Peter P. Rainer, Simon Sedej, Guido Kroemer
Summary: In this Review, Kroemer and colleagues summarize eight molecular hallmarks of cardiovascular ageing, including disabled macroautophagy, loss of proteostasis, genomic instability, epigenetic alterations, mitochondrial dysfunction, cell senescence, dysregulated neurohormonal signalling and inflammation. Targeting these hallmarks therapeutically can attenuate residual cardiovascular risk in older individuals.
NATURE REVIEWS CARDIOLOGY
(2023)
Article
Oncology
Julie Le Naour, Guido Kroemer
Summary: Accumulating evidence suggests that TLR agonists have favorable immune-activating effects and can be used as immunological adjuvants for cancer immunosurveillance. Several TLR agonists have been approved for oncological applications and extensively investigated. Clinical trials are ongoing to evaluate the combination of TLR agonists with other cancer treatments. Antibodies targeting tumor-enriched surface proteins conjugated with TLR agonists are also being developed to stimulate anticancer immune response within the tumor microenvironment. This review summarizes recent preclinical and clinical advances in TLR agonists for anticancer immunotherapy.
Article
Oncology
Vincent Carbonnier, Julie Le Naour, Thomas Bachelot, Erika Vacchelli, Fabrice Andre, Suzette Delaloge, Guido Kroemer
Summary: Formyl peptide receptor-1 (FPR1) is involved in pathogen recognition, inflammation control and cancer immunosurveillance. A single nucleotide polymorphism (SNP), rs867228, in FPR1 accelerates age at diagnosis of specific carcinomas, including luminal B breast cancer, by 4.9 years. Genetic analysis of 215 patients with metastatic luminal B breast cancer confirmed that rs867228 accelerates age of diagnosis by 6.3 years. Detection of rs867228 may be useful in breast cancer screening to start examinations at a younger age.
Article
Cell Biology
Mathilde Coulet, Sylvie Lachkar, Marion Leduc, Marc Trombe, Zelia Gouveia, Franck Perez, Oliver Kepp, Guido Kroemer, Stephane Basmaciogullari
Summary: In this study, a selective hook system called RUSH was used to identify cell secretion modulators in U2OS cells. They created a U2OS cell line that expressed a modified antibody bait and a streptavidin hook, which allowed the antibody to be retained in the endoplasmic reticulum (ER). Biotin was used to trigger the release of the antibody from the ER, resulting in its secretion.
Article
Medicine, Research & Experimental
Nicolas Gonzalo Nunez, Fiamma Berner, Ekaterina Friebel, Susanne Unger, Nina Wyss, Julia Martinez Gomez, Mette-Triin Purde, Rebekka Niederer, Maximilian Porsch, Christa Lichtensteiger, Rafaela Kramer, Michael Erdmann, Christina Schmitt, Lucie Heinzerling, Marie-Therese Abdou, Julia Karbach, Dirk Schadendorf, Lisa Zimmer, Selma Ugurel, Niklas Kluemper, Michael Hoelzel, Laura Power, Stefanie Kreutmair, Mariaelena Capone, Gabriele Madonna, Lacin Cevhertas, Anja Heider, Teresa Amaral, Omar Hasan Ali, David Bomze, Florentia Dimitriou, Stefan Diem, Paolo Antonio Ascierto, Reinhard Dummer, Elke Jaeger, Christoph Driessen, Mitchell Paul Levesque, Willem van de Veen, Markus Joerger, Martin Frueh, Burkhard Becher, Lukas Flatz
Summary: In this study, a multi-omics approach was used to characterize the systemic immune compartment of melanoma or non-small cell lung cancer patients before and during immune checkpoint inhibitor (ICI) treatment. Potential predictive biomarkers for ICI-induced immune-related adverse events (irAEs) were identified, including early increase in CXCL9/CXCL10/CXCL11 and interferon-g (IFN-g) 1 to 2 weeks after treatment initiation, as well as early expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+ CD8+ T cells.
Article
Oncology
Laurence Zitvogel, Lisa Derosa, Guido Kroemer
Summary: In patients with multiple myeloma, mRNA-based vaccination schemes failed to generate detectable SARS-CoV-2 Omicron-neutralizing antibodies in approximately 60% of the cases and S1-RBD-specific CD8+ T cells in 80% of the cases. Patients who experienced breakthrough infections had very low levels of live-virus neutralizing antibodies and lacked follicular T helper cells.
BLOOD CANCER DISCOVERY
(2023)
Review
Cell Biology
Lea Montegut, Mahmoud Abdellatif, Omar Motino, Frank Madeo, Isabelle Martins, Victor Quesada, Carlos Lopez-Otin, Guido Kroemer
Summary: Acyl coenzyme A binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), is an ancient protein that plays a role in fatty acid metabolism and has been found to have anti-aging effects. Inhibition of ACBP can extend lifespan and improve healthspan in multiple species.
Article
Oncology
Carola Berking, Elisabeth Livingstone, Dirk Debus, Carmen Loquai, Michael Weichenthal, Ulrike Leiter, Felix Kiecker, Peter Mohr, Thomas K. Eigentler, Janina Remy, Katharina Schober, Markus V. Heppt, Imke von Wasielewski, Dirk Schadendorf, Ralf Gutzmer
Summary: The outcome of advanced melanoma patients has greatly improved over the past 15 years. Targeted therapies blocking BRAF or inhibiting immune checkpoints have shown significant efficacy in improving overall survival. The COMBI-r study confirms the efficacy of dabrafenib plus trametinib in routine clinical practice and provides additional data in patients with brain metastases or previous treatments.
Article
Biochemistry & Molecular Biology
Susan Costantini, Gabriele Madonna, Elena Di Gennaro, Francesca Capone, Palmina Bagnara, Mariaelena Capone, Silvia Sale, Carmine Nicastro, Lidia Atripaldi, Giuseppe Fiorentino, Roberto Parrella, Vincenzo Montesarchio, Luigi Atripaldi, Paolo A. Ascierto, Alfredo Budillon
Summary: SARS-CoV-2 infection has a wide range of clinical manifestations, from asymptomatic to severe forms. The patients with the highest mortality rate exhibit a cytokine storm, similar to cancer-related inflammation. SARS-CoV-2 infection also leads to metabolic changes, which are closely linked to cancer metabolism. Understanding the correlation between perturbed metabolism and inflammatory responses is crucial.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Philipp Jansen, Jean Le 'Clerc Arrastia, Daniel Otero Baguer, Maximilian Schmidt, Jennifer Landsberg, Joerg Wenzel, Michael Emberger, Dirk Schadendorf, Eva Hadaschik, Peter Maass, Klaus Georg Griewank
Summary: This study highlights the enormous potential of artificial intelligence in pathology, showing that it can aid in the identification of rare cutaneous adnexal tumors and potentially become a standard tool in routine diagnostics.
EUROPEAN JOURNAL OF CANCER
(2024)