Review
Oncology
Christina Jensen, Neel Nissen, Claus S. Von Arenstorff, Morten A. Karsdal, Nicholas Willumsen
Summary: Despite the overall clinical success of ICIs for treating patients with solid tumors, a large number of patients do not benefit from this approach. The most prevalent biomarkers do not reliably predict response to ICIs across different solid tumor types, indicating a need for a broader view in predictive biomarkers. Fibrotic activity characterized by ECM and collagen production by CAFs may be a central common denominator of resistance to ICIs.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Review
Cell Biology
Oluwaseyi Adeuyan, Emily R. Gordon, Divya Kenchappa, Yadriel Bracero, Ajay Singh, Gerardo Espinoza, Larisa J. Geskin, Yvonne M. Saenger
Summary: The approval of immunotherapy for stage II-IV melanoma has highlighted the need for improved immune-based predictive and prognostic biomarkers. Several techniques are currently under investigation for the detection of prognostic and predictive immune biomarkers in melanoma.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Oncology
Ryan C. Augustin, Sarah Newman, Aofei Li, Marion Joy, Maureen Lyons, Mary P. Pham, Peter Lucas, Katelyn Smith, Cindy Sander, Brian Isett, Diwakar Davar, Yana G. Najjar, Hassane M. Zarour, John M. Kirkwood, Jason John Luke, Riyue Bao
Summary: In this study, we characterized acral melanoma (AM) and investigated its response to immune checkpoint inhibitors (ICIs). We found differential gene expression and pathway activation in a non-T cell-inflamed tumor microenvironment (TME) of AM, which may contribute to its poor response to ICIs.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Immunology
Yongmin Li, Fei Liu
Summary: Extracellular vesicles (EVs) play a crucial role in cell-to-cell communication as small particles secreted by various cell types. They have become attractive candidates for treating tumors, including melanoma, due to their involvement in multiple physiological and pathological processes. Targeting the tumor microenvironment (TME) through EVs-based therapy has emerged as a cutting-edge strategy for inhibiting melanoma progression and enhancing anti-tumor immunity. This review aims to summarize and discuss the therapeutic role of EVs that target TME components in melanoma, providing insights into promising clinical strategies for melanoma treatment.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Zhen Bian, Lei Shi, Koby Kidder, Ke Zen, Charlie Garnett-Benson, Yuan Liu
Summary: This study demonstrates that depleting SIRP alpha on intratumoral macrophages enhances the efficacy of radiotherapy to eliminate large, treatment-resistant colorectal and pancreatic tumors, inducing complete abscopal remission and long-lasting immune responses that prevent recurrence. This suggests that targeting SIRP alpha could serve as a promising strategy for treating a broad spectrum of cancers, including advanced stages with low immunogenicity and metastases.
NATURE COMMUNICATIONS
(2021)
Article
Medicine, Research & Experimental
Qian Zhang, Zi-Yi An, Wen Jiang, Wei-Lin Jin, Xin-Yang He
Summary: “Collagen, a major component of the extracellular matrix (ECM), plays a crucial role in tumor progression within the tumor microenvironment (TME). Recent studies have shown that collagen deposition in the TME affects tumor progression and interacts with tumor cells in complex ways. These findings highlight the potential of collagen as a target for cancer therapy.”
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Oncology
Gang Li, Xuran Zhu, Chao Liu
Summary: This study investigated immune cell infiltration in melanoma using different methods, finding higher infiltration in metastatic melanoma and a positive correlation with overall survival. Different immune infiltration patterns were identified, and TYRP1 was found to be negatively correlated with CD8A expression.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Anna Lorenz, Mateusz Kozlowski, Sebastian Lenkiewicz, Sebastian Kwiatkowski, Aneta Cymbaluk-Ploska
Summary: Melanoma of the vulva and vagina is a rare neoplasm with a poor prognosis. Immunotherapy, a rapidly developing cancer treatment method, has limited effectiveness for this rare type of melanoma.
Article
Oncology
Patrick Demkowicz, Renelle Pointdujour-Lim, Sofia Miguez, Yesung Lee, Bailey S. C. L. Jones, Christopher A. Barker, Marcus Bosenberg, David H. Abramson, Alexander N. Shoushtari, Harriet Kluger, Jasmine H. Francis, Mario Sznol, Mathieu F. Bakhoum
Summary: This study retrospectively analyzed clinical data of patients with metastatic uveal melanoma and found that female sex, treatment with immune checkpoint inhibitors, and the absence of liver metastasis were associated with better survival outcomes. These findings highlight the potential of immunotherapy in treating metastatic uveal melanoma.
Article
Biochemistry & Molecular Biology
Mari E. Strand, Maarten Vanhaverbeke, Michiel T. H. M. Henkens, Maurits A. Sikking, Karoline B. Rypdal, Bjorn Braathen, Vibeke M. Almaas, Theis Tonnessen, Geir Christensen, Stephane Heymans, Ida G. Lunde
Summary: Circulating biomarkers reflecting cardiac inflammation are needed to improve the diagnostics and guide the treatment of heart failure patients. The shedding of syndecan-4 from cardiac myocytes and fibroblasts was attenuated by immunomodulatory therapy. However, the levels of syndecan-4 did not reflect cardiac inflammatory status in patients with heart disease.
Article
Genetics & Heredity
Junyu Long, Dongxu Wang, Anqiang Wang, Peipei Chen, Yu Lin, Jin Bian, Xu Yang, Mingjun Zheng, Haohai Zhang, Yongchang Zheng, Xinting Sang, Haitao Zhao
Summary: The mutation-based gene set developed in this study can be used to reliably predict survival benefit across cancers in patients receiving ICI therapy. The gene set is closely associated with immune landscapes and can guide the selection of immunotherapy for cancer patients.
Article
Biology
Yin He, Xiaosheng Wang
Summary: This study aims to identify predictive biomarkers for immunotherapy response in melanoma by utilizing immunotherapy data and The Cancer Genome Atlas (TCGA) multi-omics data. The researchers identified known and novel molecular features associated with immunotherapy response at different levels, including genome, transcriptome, epigenome, and proteome. These findings provide potential biomarkers for predicting immunotherapy response and require further investigation.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Cell Biology
Han Zhao, Yun Chen, Peijun Shen, Lan Gong
Summary: This study analyzed the immune cell infiltration landscape of uveal melanoma using CIBERSORT and ESTIMATE algorithms, finding that patients with high ICI scores had poorer prognosis and increased expression levels of immune checkpoint-related genes. The study demonstrated that ICI scores are an independent prognostic biomarker and have value in predicting immunotherapeutic outcomes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Genetics & Heredity
Yanding Zhao, Yadong Dong, Yongqi Sun, Chao Cheng
Summary: This study identified two gene signatures capturing intrinsic and extrinsic features in melanoma using TCGA RNA-seq data. By decomposing gene expression into representative nodes, the study found nodes significantly associated with patient prognosis, leading to the definition of tumor-intrinsic and tumor-extrinsic signatures. These signatures were able to predict patient prognosis and were positively associated with patient response to immunotherapies.
FRONTIERS IN GENETICS
(2021)
Article
Oncology
Wolfram Samlowski, Camille Adajar
Summary: In patients with progressing melanoma after initial checkpoint inhibitor therapy, the addition of BRAF +/- MEK inhibitors to continued PD-1 antibody treatment as second line therapy showed substantial activity and manageable toxicity. This approach can induce durable complete responses in patients who have failed initial immunotherapy, suggesting further evaluation in suitable patients.
Letter
Dermatology
Signe Holm Nielsen, Solveig Skovlund Groen, Yiqiu Yao, Astrid-Helene Ravn Jorgensen, Valdemar Wendelboe Nielsen, Morten Karsdal, Kristoffer Gehring, Anne-Christine Bay-Jensen, Simon Francis Thomsen
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Oncology
Eva Ellebaek, Aimilia Schina, Henrik Schmidt, Charlotte Aaquist Haslund, Lars Bastholt, Inge Marie Svane, Marco Donia
Summary: This study found that initiation of immunotherapy in summer is associated with prolonged survival in patients with BRAF wild-type melanoma in Denmark.
PIGMENT CELL & MELANOMA RESEARCH
(2023)
Article
Transplantation
Daan Kremer, Firas F. Alkaff, Adrian Post, Tim J. Knobbe, Martin Tepel, Olivier Thaunat, Stefan P. Berger, Jacob van den Born, Federica Genovese, Morten A. Karsdal, Daniel G. K. Rasmussen, Stephan J. L. Bakker, Behalf Transplant Lines Investigators
Summary: This study found a strong association between plasma endotrophin and graft failure and mortality in kidney transplant recipients. The findings suggest that abnormal extracellular matrix turnover and fibrosis play a key role in the prognosis of kidney transplant recipients and highlight the need for interventional studies targeting the profibrotic state of these patients.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Orthopedics
I. Hellberg, V. -P. Karjalainen, M. A. J. Finnilä, E. Jonsson, A. Turkiewicz, P. Önnerfjord, V. Hughes, J. Tjörnstrand, M. Englund, S. Saarakkala
Summary: This study proposed a micro-computed tomography (mu CT) based 3D analysis of meniscal calcifications ex vivo, including a new grading system. The results showed that mu CT images can effectively depict meniscal calcifications, and the new grading system can accurately measure the severity of meniscal calcification. Two different patterns of degeneration were observed.
OSTEOARTHRITIS AND CARTILAGE
(2023)
Article
Medicine, General & Internal
Nicklas Juel Spindler, Gitte Fredberg Persson, Susann Theile, Dorte Lisbeth Nielsen, Estrid Hogdall, Gina Al-Farra, Helle Westergren Hendel, Torben Lorentzen, Inge Marie Svane, Henriette Lindberg, Rikke Lovendahl Eefsen
Summary: This study aims to investigate the efficacy of combining SBRT and CPI treatment in patients with mCRPC. A total of 80 evaluable patients who have progressed after multiple lines of treatment will be enrolled and receive ipilimumab and nivolumab combination therapy, with some patients also receiving SBRT. The primary endpoints are objective response rate and PSA response rate, and secondary endpoints include safety, radiographic progression-free survival, clinical benefit rate, duration of response, PSA-progression-free survival beyond 12 weeks, quality of life, and overall survival. The results will be published in an international peer-reviewed journal.
Letter
Gastroenterology & Hepatology
Emilie Dahl, Osama Abed, Jorgen Agnholt, Jacob Bjerrum, Anders Dige, Jens Kjeldsen, Inge Svane, Marco Donia, Jakob Seidelin
Summary: This article is linked to Dahl et al papers. To view these articles, visit...
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Oncology
Neel Maria Helvind, Marie Brinch-Moller Weitemeyer, Annette Hougaard Chakera, Helle Westergren Hendel, Eva Ellebaek, Inge Marie Svane, Mette Wanscher Kjaerskov, Sophie Bojesen, Helle Skyum, Soren Kjaer Petersen, Lars Bastholt, Christoffer Johansen, Pernille Envold Bidstrup, Lisbet Rosenkrantz Holmich
Summary: This study aimed to determine the impact of surveillance with routine FDG PET-CT on hazard, cumulative incidence, and absolute risk of overall, locoregional, and distant recurrence detection in patients with stage IIB to IIID cutaneous melanoma. The study found that patients with stage IIB to IIID melanoma followed with routine FDG PET-CT had a 51% increased hazard of distant recurrence detection within the first two years of surveillance.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Orthopedics
Martin Ryden, Karin Lindblom, Aida Yifter-Lindgren, Aleksandra Turkiewicz, Anders Aspberg, Viveka Tillgren, Martin Englund, Patrik Onnerfjord
Summary: Degenerative meniscus lesions have been associated with both osteoarthritis etiology and its progression. In this study, a human meniscus ex vivo model was established to study the meniscal response to cytokine treatment using proteomics. The results showed that IL1β treatment increased the release of cytokines, while OSM+TNF and TNF+IL6+sIL6R treatments induced catabolic effects, which may contribute to the development of osteoarthritis.
JOURNAL OF ORTHOPAEDIC RESEARCH
(2023)
Article
Biochemical Research Methods
Martin Ryden, Aleksandra Turkiewicz, Patrik Onnerfjord, Jon Tjornstrand, Martin Englund, Neserin Ali
Summary: This study aimed to characterize the degradome of knee osteoarthritis (OA) patients by analyzing proteolytic activity and differential abundance of cleavage products in synovial fluid (SF). Liquid chromatography mass spectrometry (LC-MS) was used to analyze SF samples from end-stage knee OA patients and controls, and a new database search was performed to identify non-tryptic and semi-tryptic peptides for degradomics studies in OA. Linear mixed models were used to estimate differences in peptide-level expression between the two groups. Known proteolytic events from the MEROPS peptidase database were mapped to the dataset to identify potential proteases and their substrates. A total of 429 differentially abundant peptides were identified, and metalloproteinases, chymase, and cathepsins were found to be the main proteolytic actors. The analysis indicated increased activity of these proteases regardless of their abundance.
Article
Oncology
Cathrine Lund Lorentzen, Julie Westerlin Kjeldsen, Eva Ehrnrooth, Mads Hald Andersen, Inge Marie Svane
Summary: Summary: This study presented the long-term follow-up results of the IDO/PD-L1 vaccine and nivolumab combination therapy in cohort A, showing promising efficacy with high overall response rates and durable responses. However, cohort B did not show significant clinical effects.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Gastroenterology & Hepatology
Mette J. Nielsen, Grace E. Dolman, Rebecca Harris, Peder Frederiksen, Jane Chalmers, Jane I. Grove, William L. Irving, Morten A. Karsdal, Keyur Patel, Diana Julie Leeming, Indra Neil Guha
Summary: This study investigated the prognostic value of the fibrogenesis marker PRO-C3 and the ALBI score in predicting clinical outcomes and mortality in two cohorts of compensated cirrhosis patients. The results showed that both PRO-C3 and ALBI were independently associated with liver-related clinical outcomes, suggesting that PRO-C3 may be a valuable predictor of treatment efficacy.
Article
Oncology
Anne Vest Soerensen, Jakob Kjellberg, Rikke Ibsen, Lars Bastholt, Henrik Schmidt, Inge Marie Svane
Summary: This study aimed to investigate the health care costs and loss of productivity after implementing new agents for metastatic melanoma. The results showed that the implementation of targeted therapy and checkpoint inhibitors increased medicine costs more than three-fold for long-term survivors. However, total health care costs excluding medicine costs were lower for long-term survivors in 2012-2016 compared to 2007-2011. Importantly, productivity increased for long-term survivors in 2012-2016.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Gastroenterology & Hepatology
Morten A. Karsdal, Kate Hallsworth, Jadine Scragg, Diana J. Leeming, Ida F. Villesen, Leah Avery, Laura Haigh, Olivier Govaere, Sarah Wichmann, Guy Taylor, Sophie Cassidy, Stuart Mcpherson, Quentin M. Anstee
Summary: The amount of fibroblast activity in patients with NAFLD can be defined by circulating biomarkers of collagen formation. The high-risk, high-fibrogenesis patient endotype with greater fibroblast activity exhibited a marked reduction in collagen fibrogenesis with a very low-calorie diet intervention, while fibrogenesis remained unchanged in the low activity group. The quantification of fibrogenesis biomarkers at baseline can predict the likelihood of treatment response.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Mohammed Ghiboub, Matthew Bell, Dovile Sinkeviciute, Rab K. Prinjha, Menno P. J. de Winther, Nicola R. Harker, David F. Tough, Wouter J. de Jonge
Summary: SP140 is a reader protein expressed in immune cells and is associated with autoimmune and inflammatory diseases. Inhibition of SP140 with GSK761 reduces the expression of inflammatory cytokines in macrophages and impairs the maturation of dendritic cells. The study suggests that targeting SP140 may be beneficial in autoimmune and inflammatory diseases.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)