Review
Immunology
Zena N. Willsmore, Ben G. T. Coumbe, Silvia Crescioli, Sara Reci, Ayushi Gupta, Robert J. Harris, Alicia Chenoweth, Jitesh Chauhan, Heather J. Bax, Alexa McCraw, Anthony Cheung, Gabriel Osborn, Ricarda M. Hoffmann, Mano Nakamura, Roman Laddach, Jenny L. C. Geh, Alastair MacKenzie-Ross, Ciaran Healy, Sophia Tsoka, James F. Spicer, Debra H. Josephs, Sophie Papa, Katie E. Lacy, Sophia N. Karagiannis
Summary: CTLA-4 and PD-1 are immune checkpoint molecules that are targets of antibody immunotherapies for malignant melanoma. Combination therapy with immune checkpoint inhibitors may have better outcomes compared to monotherapy in certain patient groups, but also presents challenges and increased rates of adverse events.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Oncology
Simon Fietz, Romina Zarbl, Dennis Niebel, Christian Posch, Peter Brossart, Gerrit H. Gielen, Sebastian Strieth, Torsten Pietsch, Glen Kristiansen, Friedrich Bootz, Jennifer Landsberg, Dimo Dietrich
Summary: CTLA4 methylation is a predictive biomarker for response to anti-CTLA-4 immunotherapy, significantly associated with progressive tumors and progression-free survival.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Multidisciplinary Sciences
Brianna M. Lax, Joseph R. Palmeri, Emi A. Lutz, Allison Sheen, Jordan A. Stinson, Lauren Duhamel, Luciano Santollani, Alan Kennedy, Adrienne M. Rothschilds, Stefani Spranger, David M. Sansom, K. Dane Wittrup
Summary: Anti-CTLA-4 antibodies have limited long-term benefit in tumor regression. We engineered a nonantagonistic CTLA-4 binding domain and found that both CTLA-4 antagonism and intratumoral Treg depletion are needed for maximum efficacy in anti-CTLA-4 therapy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Immunology
B. Leticia Rodriguez, Limo Chen, Yanli Li, Shucheng Miao, David H. Peng, Jared J. Fradette, Lixia Diao, Jessica M. Konen, Frank R. Rojas Alvarez, Luisa M. Solis, Xiaohui Yi, Aparna Padhye, Laura A. Gibson, Joshua K. Ochieng, Xiaofei Zhou, Jing Wang, Don L. Gibbons
Summary: The resistance to immune checkpoint blockade (ICB) therapy in non-small cell lung cancer (NSCLC) is associated with infiltrating monocytes, and controlling the differentiation process of monocytes can enhance the therapeutic potential of ICB.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Prachi Bhave, Tasnia Ahmed, Serigne N. Lo, Alexander Shoushtari, Anne Zaremba, Judith M. Versluis, Joanna Mangana, Michael Weichenthal, Lu Si, Thierry Lesimple, Caroline Robert, Claudia Trojanello, Alexandre Wicky, Richard Heywood, Lena Tran, Kathleen Batty, Florentia Dimitriou, Anna Stansfeld, Clara Allayous, Julia K. Schwarze, Meghan J. Mooradian, Oliver Klein, Inderjit Mehmi, Rachel Roberts-Thomson, Andrea Maurichi, Hui-Ling Yeoh, Adnan Khattak, Lisa Zimmer, Christian U. Blank, Egle Ramelyte, Katharina C. Kaehler, Severine Roy, Paolo A. Ascierto, Olivier Michielin, Paul C. Lorigan, Douglas B. Johnson, Ruth Plummer, Celeste Lebbe, Bart Neyns, Ryan Sullivan, Omid Hamid, Mario Santinami, Grant A. McArthur, Andrew M. Haydon, Georgina Long, Alexander M. Menzies, Matteo S. Carlino
Summary: Acral melanoma is a rare subtype with poor prognosis, and there is a lack of prospective clinical trial evidence on the efficacy of checkpoint inhibitors in this population. The study found that initial anti-PD-1/ipilimumab combination had a significantly higher ORR compared to anti-PD-1 alone, but this benefit did not translate to improved OS in this retrospective cohort. Primary site did not impact treatment outcomes.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Tuba N. Gide, Ines Pires da Silva, Camelia Quek, Peter M. Ferguson, Marcel Batten, Ping Shang, Tasnia Ahmed, Alexander M. Menzies, Matteo S. Carlino, Robyn P. M. Saw, John F. Thompson, Richard A. Scolyer, Georgina V. Long, James S. Wilmott
Summary: While immune checkpoint inhibitors targeting CTLA-4 and PD-1 have improved outcomes for many patients with metastatic melanoma, there remains a subset of patients who do not respond. This study identified two distinct groups of non-responders based on their gene expression profiles, highlighting the importance of a personalized approach for identifying effective treatments for anti-PD-1 resistant patients.
Article
Immunology
Ying Zhang, Xiaolong Wu, Amit Sharma, Hans Weiher, Matthias Schmid, Glen Kristiansen, Ingo G. H. Schmidt-Wolf
Summary: The study found that anti-CD40 antibody can increase the number of CD3+CD56+ effector cells in CIK cells by promoting the maturation and activation of dendritic cells. In addition, anti-CD40 antibody can also increase the expression of CTLA-4 in CIK cells. For the antitumor response of DC-CIK cells against renal cell carcinoma cells, anti-CD40 antibody is superior to anti-CTLA-4 antibody. The CTLA-4 inhibitor ipilimumab can significantly increase the proportion of CD3+CD56+ cells in DC-CIK cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Lauren J. Brown, Alison Weppler, Prachi Bhave, Clara Allayous, J. Randall Patrinely, Patrick Ott, Shahneen Sandhu, Andrew Haydon, Celeste Lebbe, Douglas B. Johnson, Georgina V. Long, Alexander A. Menzies, Matteo S. Carlino
Summary: This study retrospectively analyzed 55 patients with advanced melanoma who received combination therapy of ipilimumab and anti-PD1, showing that in patients with pre-existing autoimmune diseases not on immunosuppression, the safety and efficacy of combination therapy were similar to previously reported trials. However, there may be a risk of flare of pre-existing autoimmune diseases in certain patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Katie M. Campbell, Meelad Amouzgar, Shannon M. Pfeiffer, Timothy R. Howes, Egmidio Medina, Michael Travers, Gabriela Steiner, Jeffrey S. Weber, Jedd D. Wolchok, James Larkin, F. Stephen Hodi, Silvia Boffo, Lisa Salvador, Daniel Tenney, Tracy Tang, Marshall A. Thompson, Christine N. Spencer, Daniel K. Wells, Antoni Ribas
Summary: Immune checkpoint inhibitors (ICIs) such as CTLA-4 and PD-1-blocking antibodies have significant effects on tumor immune cell infiltration. In this study, we analyzed molecular datasets from 514 patients with advanced melanoma to explore the features of anti-PD-1 response. We found that prior anti-CTLA-4 therapy is associated with genomic and transcriptomic differences in anti-PD-1 responders, suggesting that the tumor microenvironment plays a role in predicting the response to PD-1 blockade therapy.
Article
Oncology
Yasuhiro Nakamura, Kenjiro Namikawa, Yukiko Kiniwa, Hiroshi Kato, Osamu Yamasaki, Shusuke Yoshikawa, Takeo Maekawa, Shigeto Matsushita, Tatsuya Takenouchi, Takashi Inozume, Yasuo Nakai, Satoshi Fukushima, Shintaro Saito, Atsushi Otsuka, Noriki Fujimoto, Taiki Isei, Natsuki Baba, Taisuke Matsuya, Ryo Tanaka, Takahide Kaneko, Masazumi Onishi, Yutaka Kuwatsuka, Kotaro Nagase, Takehiro Onuma, Motoo Nomura, Yoshiyasu Umeda, Naoya Yamazaki
Summary: This study compared the efficacy of PD-1 and PD-1+CTLA-4 for the treatment of advanced AM in Japanese patients. The results showed no significant differences in ORR, PFS, and OS between the two groups in PSM patients. In NAM patients, the PD-1+CTLA-4 group had significantly higher ORR and longer PFS, and PD-1+CTLA-4 was identified as an independent predictor of favorable PFS in NAM patients.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Oncology
Megan M. Y. Hong, Saman Maleki Vareki
Summary: Immunotherapy has revolutionized the treatment of advanced cancers by utilizing the immune system to target tumor cells. CTLA-4-targeting agents can release the brakes on the immune system to promote anti-tumor immune responses. While anti-CTLA-4 therapy can confer long-lasting clinical benefits, patient response rates remain relatively low.
Article
Biotechnology & Applied Microbiology
Lei Lv, Qinqin Wei, Zhiwen Wang, Yujia Zhao, Ni Chen, Qiyi Yi
Summary: NLRC5 plays a tumor suppressor role in melanoma by modulating the tumor immune microenvironment. Its expression is regulated by various factors and is closely associated with clinical characteristics, immune features, and treatment efficacy in melanoma. Targeting the NLRC5 pathway may improve immunotherapy effectiveness for melanoma patients.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Immunology
Han Gao, Rui-zhi Chang, Xiao-ping Chen, Wan-guang Zhang, Bixiang Zhang, Xin Luo, Ze-yang Ding
Summary: This is a case report on hepatocellular carcinoma (HCC) associated with hepatitis B. The study found that HCC patients with asymptomatic hyperamylasemia may benefit from combined immunotherapy with anti-CTLA-4 and PD-1 antibodies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Kristina Witt, Susan Evans-Axelsson, Andreas Lundqvist, Martin Johansson, Anders Bjartell, Rebecka Hellsten
Summary: The combination of STAT3 inhibition with anti-CTLA-4 therapy enhances antitumoral activity in prostate cancer, reducing intratumoral Treg frequency.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Oncology
Melissa L. Bastacky, Hong Wang, Dylan Fortman, Zahra Rahman, Gerard P. Mascara, Timothy Brenner, Yana G. Najjar, Jason J. Luke, John M. Kirkwood, Hassane M. Zarour, Diwakar Davar
Summary: This study of 190 metastatic melanoma patients treated with single-agent anti-PD-1 ICI therapy found that 60% experienced at least one immune-related adverse event (irAEs), with irAE occurrence significantly associated with response to anti-PD-1 therapy. Patients with multiple irAEs exhibited distinct patterns, and obesity was distinctly associated with irAE development, while age and gender showed no significant association.
FRONTIERS IN ONCOLOGY
(2021)
Article
Pharmacology & Pharmacy
Remya Valsalakumari, Sunil Kumar Yadava, Marzena Szwed, Abhilash D. Pandya, Gunhild Mari Maelandsmo, Maria Lyngaas Torgersen, Tore-Geir Iversen, Tore Skotland, Kirsten Sandvig, Jyotsnendu Giri
Summary: The study found that LNCs-PTX were taken up by MDA-MB-468 cells more effectively than the other two cell lines. Additionally, the cytotoxicity of LNCs-PTX on cells was primarily attributed to endocytosis mechanisms involving Cdc42/GRAF-dependent endocytosis and macropinocytosis.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Biotechnology & Applied Microbiology
Pierre Dillard, Hakan Koksal, Solrun Melkorka Maggadottir, Anna Winge-Main, Sylvie Pollmann, Mathilde Menard, Marit Renee Myhre, Gunhild M. Maelandsmo, Vivi Ann Florenes, Gustav Gaudernack, Gunnar Kvalheim, Sebastien Walchli, Else Marit Inderberg
Summary: A novel hTERT-specific TCR sequence, named Radium-4, was isolated from a pancreatic cancer patient vaccinated with a long hTERT peptide, showing promising efficacy in killing malignant tumor cells without toxicity to normal hematopoietic cells. This TCR has a high population coverage and represents an attractive candidate for immunotherapy of solid tumors.
Article
Oncology
Anna Barkovskaya, Craig M. Goodwin, Kotryna Seip, Bylgja Hilmarsdottir, Solveig Pettersen, Clint Stalnecker, Olav Engebraaten, Eirikur Briem, Channing J. Der, Siver A. Moestue, Thorarinn Gudjonsson, Gunhild M. Maelandsmo, Lina Prasmickaite
Summary: By utilizing CRISPR-Cas9 technology, researchers identified differences in genetic vulnerabilities between epithelial and mesenchymal phenotype cells, providing crucial insights for discovering actionable targets and promising therapeutic combinations.
MOLECULAR ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Karianne Giller Fleten, J. Johannes Eksteen, Brynjar Mauseth, Ketil Andre Camilio, Terje Vasskog, Baldur Sveinbjornsson, Oystein Rekdal, Gunhild M. Maelandsmo, Kjersti Flatmark
Summary: The study found that oncolytic peptides showed promising activity in treating CRC and produced good therapeutic effects in mouse models. Experimental evidence demonstrated that these oncolytic peptides can trigger lasting anticancer immune responses and prevent the occurrence of liver metastases, making them potentially promising drugs for the treatment of colorectal cancer in the future.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Multidisciplinary
Abhilash D. Pandya, Tore-Geir Iversen, Siver Moestue, Maria T. Grinde, Yrr Morch, Sofie Snipstad, Andreas K. O. Aslund, Geir F. Oy, Wanja Kildal, Olav Engebraten, Kirsten Sandvig, Tore Skotland, Gunhild M. Maelandsmo
Summary: PEBCA nanoparticles showed the highest uptake in breast cancer xenografts and lymph nodes, making them the most promising for drug delivery. They also increased infiltration of anti-tumorigenic M1 macrophages in tumors and shifted the M1/M2 macrophage ratio, suggesting potential for modulating immune responses for enhanced therapeutic effects.
Article
Biochemistry & Molecular Biology
Mateusz A. Krzyscik, Malgorzata Zakrzewska, Vigdis Sorensen, Geir Frode Oy, Skjalg Brunheim, Ellen M. Haugsten, Gunhild M. Maelandsmo, Antoni Wiedlocha, Jacek Otlewski
Summary: Despite being the second leading cause of death worldwide, cancer still lacks a fully effective therapy, highlighting the urgent need for new targeted anticancer drugs. Researchers have developed novel protein-drug conjugates that successfully inhibit tumor growth in a mouse model of human breast cancer.
Article
Oncology
Sigurdur Trausti Karvelsson, Arnar Sigurdsson, Kotryna Seip, Maria Tunset Grinde, Qiong Wang, Freyr Johannsson, Gunhild Mari Maelandsmo, Siver Andreas Moestue, Ottar Rolfsson, Skarphedinn Halldorsson
Summary: The study reveals that the epithelial-to-mesenchymal transition induces metabolic changes in breast epithelial cells, including re-routing of the TCA cycle, increased lipid biosynthesis, and decreased glycolytic rates. The alterations in GSH synthesis modulate the sensitivity of breast epithelial cells to mTOR inhibitors.
MOLECULAR CANCER RESEARCH
(2021)
Article
Endocrinology & Metabolism
Caroline E. Nunes-Xavier, Wanja Kildal, Andreas Kleppe, Havard E. Danielsen, Hakon Waehre, Roberto Llarena, Gunhild M. Maelandsmo, Oystein Fodstad, Rafael Pulido, Jose I. Lopez
Summary: This study identified distinct clinical relevance of the two immune checkpoint proteins PD-L1 and B7-H3 in prostate cancer, with B7-H3 potentially serving as a significant therapeutic target.
Article
Multidisciplinary Sciences
Lisa Svartdal Normann, Miriam Ragle Aure, Suvi-Katri Leivonen, Mads Haugland Haugen, Vesa Hongisto, Vessela N. Kristensen, Gunhild Mari Maelandsmo, Kristine Kleivi Sahlberg
Summary: HER2-positive breast cancer patients that do not respond to targeted treatment have a poor prognosis. Through a high-throughput screen, it was found that certain miRNA mimics can sensitize HER2+ breast cancer cells to targeted therapy, with miR-101-5p showing a correlation with better prognosis in patients. This suggests the potential of combining targeted drugs with miRNAs to improve current treatments for HER2+ breast cancers.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Marta Nyakas, Karianne Giller Fleten, Mads Haugland Haugen, Nikolai Engedal, Christina Sveen, Inger Nina Farstad, Vivi Ann Florenes, Lina Prasmickaite, Gunhild Mari Maelandsmo, Kotryna Seip
Summary: This study investigated the therapeutic potential of combining an AXL inhibitor (AXLi) and a clinically relevant BRAF inhibitor (BRAFi) for the treatment of metastatic melanoma. The results showed that AXL was expressed in the majority of melanoma lymph node metastases. In vitro experiments demonstrated that the combination of AXLi and BRAFi resulted in the largest reduction in cell viability. Moreover, pre-clinical studies using AXL(high) melanoma models showed a therapeutic benefit of adding AXLi to the BRAF-targeted therapy. Mechanistic insights revealed that AXLi potentiated BRAFi-induced apoptosis, stimulated ferroptosis, and inhibited autophagy. Overall, this study suggests that combining AXLi with standard therapy could improve the therapeutic outcome in metastatic melanoma.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Caroline E. Nunes-Xavier, Janire Mingo, Maite Emaldi, Karine Flem-Karlsen, Gunhild M. Maelandsmo, Oystein Fodstad, Roberto Llarena, Jose I. Lopez, Rafael Pulido
Summary: This study revealed heterogeneous expression of PDH complex components in PCa tumors, with PDH complex components being related to AR signaling and PDK2 expression associated with poor PCa prognosis. These findings highlight the potential of targeting PDH complex components for intervention in PCa.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Alexander N. Shoushtari, Anthony J. Olszanski, Marta Nyakas, Thomas J. Hornyak, Jedd D. Wolchok, Victor Levitsky, Lukasz Kuryk, Thomas B. Hansen, Magnus Jaderberg
Summary: This study investigated the efficacy of ONCOS-102 (an oncolytic adenovirus expressing GM-CSF) combined with anti-PD-1 therapy in patients with anti-PD-1-resistant melanoma. The results showed that the combination treatment was well tolerated and resulted in clinical benefit by promoting T-cell infiltration, particularly cytotoxic CD8+ T cells, in the tumor microenvironment.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Caroline Robert, Matteo S. Carlino, Catriona Mcneil, Antoni Ribas, Jean-Jacques Grob, Jacob Schachter, Marta Nyakas, Damien Kee, Teresa M. Petrella, Arnold Blaustein, Michal Lotem, Ana Arance, Adil I. Daud, Omid Hamid, James Larkin, James Anderson, Clemens Krepler, Dmitri Grebennik, Georgina V. Long
Summary: Clinical trials often have multiple end points that mature at different times. Clinical Trial Updates provide a platform to publish additional results from studies where the primary end point has already been reported. This article presents the 7-year follow-up and efficacy results of pembrolizumab in advanced melanoma patients.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Vigdis Nygaard, Anne Hansen Ree, Vegar Johansen Dagenborg, Anne-Lise Borresen-Dale, Bjorn Edwin, Asmund Avdem Fretland, Krzysztof Grzyb, Mads H. Haugen, Gunhild M. Maelandsmo, Kjersti Flatmark
Summary: A mesenchymal subgroup with an immunosuppressive phenotype, characterized by high expression of immune checkpoints HAVCR2/TIM-3 and VISTA, as well as the M2 macrophage marker CD163, was identified in colorectal cancer liver metastases. These findings suggest potential novel opportunities for immune-based therapy approaches in microsatellite stable colorectal cancer.
CANCER RESEARCH COMMUNICATIONS
(2023)
Article
Oncology
Margherita Ambrosini, Marzia Del Re, Paolo Manca, Andrew Hendifar, Alexander Drilon, Guilherme Harada, Anne Hansen Ree, Samuel Klempner, Gunhild Mari Maelandsmo, Kjersti Flatmark, Hege G. Russnes, James M. Cleary, Harshabad Singh, Elisa Sottotetti, Antonia Martinetti, Giovanni Randon, Andrea Sartore-Bianchi, Iolanda Capone, Massimo Milione, Maria Di Bartolomeo, Filippo Pietrantonio
Summary: This study collected data from patients with GI cancers and ALK rearrangements, showing remarkable responses and clinical benefit with ALK inhibitors. Despite the low frequency, ALK rearrangements play an important role in personalized treatment for GI cancers.
JCO PRECISION ONCOLOGY
(2022)
