Review
Biochemistry & Molecular Biology
David Escors, Ana Bocanegra, Luisa Chocarro, Ester Blanco, Sergio Pineiro-Hermida, Maider Garnica, Leticia Fernandez-Rubio, Ruth Vera, Hugo Arasanz, Grazyna Kochan
Summary: PD-L1/PD-1 blockade immunotherapy has revolutionized cancer treatment, but its mechanisms and effectiveness are still not fully understood. This article reviews the evidence supporting the role of CD4 T cells in anti-tumor immunity and their potential as predictors of response to PD-L1/PD-1 blockade immunotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Immunology
Katherine Kedzierska, Thi H. O. Nguyen
Summary: The study by Wherry and colleagues examines how anti-PD-1 immunotherapy affects influenza vaccination outcomes in cancer patients, specifically looking at its impact on seroconversion and quantitative and qualitative aspects of antibodies and follicular T helper cell responses.
Article
Oncology
J. Tobias, P. Steinberger, M. Drinic, U. Wiedermann
Summary: Inhibition of the PD-1/PD-L1 pathway with monoclonal antibodies has transformed cancer therapy, but has limitations such as lack of response in many patients and high costs. Small peptides that interfere with PD-1/PD-L1 interaction offer an interesting alternative. Peptides representing PD-1 or PD-L1 sequences can be combined with cancer antigen-derived peptides to induce an effective antitumor immune response.
Article
Medicine, Research & Experimental
Camille-Charlotte Balanca, Anna Salvioni, Clara-Maria Scarlata, Marie Michelas, Carlos Martinez-Gomez, Carlos Gomez-Roca, Victor Sarradin, Marie Tosolini, Carine Valle, Frederic Pont, Gwenael Ferron, Laurence Gladieff, Sebastien Vergez, Agnes Dupret-Bories, Eliane Mery, Philippe Rochaix, Jean-Jacques Fournie, Jean-Pierre Delord, Christel Devaud, Alejandra Martinez, Maha Ayyoub
Summary: Tumor antigen-specific CD4 T cells exhibit exhaustion in patients with head and neck, cervical, and ovarian cancer, characterized by high PD-1 and CD39 expression and low cytokine secretion despite functional presence. Terminal exhaustion of CD4 T cells is observed regardless of TIM-3 expression, suggesting divergence from CD8 T cell exhaustion. PD-1 blockade enhances CD4 T cell activation and promotes dendritic cell maturation, leading to improved tumor-specific CD8 T cell proliferation.
Review
Oncology
Mengling Wu, Qianrui Huang, Yao Xie, Xuyi Wu, Hongbo Ma, Yiwen Zhang, Yong Xia
Summary: PD-1/PD-L1 immune checkpoints inhibit the anticancer effect of T cells in the tumor microenvironment, and downregulation or upregulation of PD-L1 expression can improve the efficacy of anti-PD-1/PD-L1 treatment. Overcoming the current limitations of this treatment can expand its anticancer applications and improve patient response rates and survival time.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Gladys Ferrere, Maryam Tidjani Alou, Peng Liu, Anne-Gaelle Goubet, Marine Fidelle, Oliver Kepp, Sylvere Durand, Valerio Iebba, Aurelie Fluckiger, Romain Daillere, Cassandra Thelemaque, Claudia Grajeda-Iglesias, Carolina Alves Costa Silva, Fanny Aprahamian, Deborah Lefevre, Liwei Zhao, Bernhard Ryffel, Emeline Colomba, Monica Arnedos, Damien Drubay, Conrad Rauber, Didier Raoult, Francesco Asnicar, Tim Spector, Nicola Segata, Lisa Derosa, Guido Kroemer, Laurence Zitvogel
Summary: Limited experimental evidence suggests a link between nutrition and cancer immunosurveillance. This study demonstrates that ketogenic diet induces an anti-tumor effect through 3HB-mediated T cell-mediated cancer immunosurveillance. 3HB prevents immune checkpoint inhibition and promotes the expansion of specific T cells, while KD also leads to compositional changes in gut microbiota.
Article
Cell Biology
Tetje C. van der Sluis, Guillaume Beyrend, Esme T. I. van der Gracht, Tamim Abdelaal, Simon P. Jochems, Robert A. Belderbos, Thomas H. Wesselink, Suzanne van Duikeren, Floortje J. van Haften, Anke Redeker, Laura F. Ouboter, Elham Beyranvand Nejad, Marcel Camps, Kees L. M. C. Franken, Margot M. Linssen, Peter Hohenstein, Noel F. C. C. de Miranda, Hailiang Mei, Adriaan D. Bins, John B. A. G. Haanen, Joachim G. Aerts, Ferry Ossendorp, Ramon Arens
Summary: Immune checkpoint therapy (ICT) has the potential to eliminate cancer, but the underlying mechanisms determining its effectiveness are not fully understood. By using high-dimensional single-cell profiling, this study investigates if the T cell landscape in peripheral blood can predict responses to combinatorial targeting of the OX40 costimulatory and PD-1 inhibitory pathways. The findings reveal dynamic activation states of therapy-responsive T cells and emphasize the importance of NK cell receptors and chemokine receptors in therapy-induced anti-tumor immunity.
CELL REPORTS MEDICINE
(2023)
Article
Oncology
Arielle Elkrief, Joao M. Victor Alessi, Biagio Ricciuti, Samantha Brown, Hira Rizvi, Isabel R. Preeshagul, Xinan Wang, Federica Pecci, Alessandro Di Federico, Giuseppe Lamberti, Jacklynn Egger, Jamie E. Chaft, Charles M. Rudin, Gregory J. Riely, Mark G. Kris, Marc Ladanyi, Yuan Chen, Matthew D. Hellmann, Ronglai Shen, Mark M. Awad, Adam J. Schoenfeld
Summary: This study compared the first-line efficacy of single-agent immunotherapy to chemotherapy combined with immunotherapy in patients with advanced lung adenocarcinoma. The results showed that chemotherapy combined with immunotherapy improved the objective response rate and progression-free survival in patients with tumor PD-L1 expression ≥1%. Among patients with PD-L1 expression ≥50%, never-smokers derived a better survival benefit from chemotherapy combined with immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Chemistry, Multidisciplinary
Yingying Hu, Lin Lin, Zhaopei Guo, Jie Chen, Atsushi Maruyama, Huayu Tian, Xuesi Chen
Summary: The researchers proposed a synergistic strategy combining in situ vaccination and gene-mediated anti-PD therapy, delivering CpG and pshPD-L1 genes using PEI as the carrier to form nanoparticles which showed synergistic antitumor efficacy in a mouse tumor model.
CHINESE CHEMICAL LETTERS
(2021)
Article
Medicine, Research & Experimental
Joseph S. Dolina, Joey Lee, Spencer E. Brightman, Sara McArdle, Samantha M. Hall, Rukman R. Thota, Karla S. Zavala, Manasa Lanka, Ashmitaa Logandha Ramamoorthy Premlal, Jason A. Greenbaum, Ezra E. W. Cohen, Bjoern Peters, Stephen P. Schoenberger
Summary: This study explores how the response to immune checkpoint blockade can be improved for aggressive low-TMB squamous cell tumors by combining intermolecular epitope spreading and immune checkpoint blockade, leading to the eradication of established large tumors.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Oncology
Hiroshi Kagamu, Satoshi Yamasaki, Shigehisa Kitano, Ou Yamaguchi, Atsuto Mouri, Ayako Shiono, Fuyumi Nishihara, Yu Miura, Kosuke Hashimoto, Hisao Imai, Kyoichi Kaira, Kunihiko Kobayashi, Yae Kanai, Tatsuhiro Shibata, Katsuhisa Horimoto
Summary: CD4(+) T-cell immunity is essential in antitumor immune responses. A new CD4(+) T-cell metacluster associated with the efficacy of PD-1 blockade therapy has been identified, which can predict the progression-free survival and overall survival of lung cancer patients after PD-1 blockade therapy.
Article
Oncology
Minglu Xiao, Luoyingzi Xie, Guoshuai Cao, Shun Lei, Pengcheng Wang, Zhengping Wei, Yuan Luo, Jingyi Fang, Xingxing Yang, Qizhao Huang, Lifan Xu, Junyi Guo, Shuqiong Wen, Zhiming Wang, Qing Wu, Jianfang Tang, Lisha Wang, Xiangyu Chen, Cheng Chen, Yanyan Zhang, Wei Yao, Jianqiang Ye, Ran He, Jun Huang, Lilin Ye
Summary: The study demonstrates that heterologous prime-boost vaccination can effectively inhibit tumor growth and enhance the expansion, effector function, and clonal breadth of tumor-specific CD8(+) T cells. Additionally, this vaccination strategy also enhances the antitumor effects of PD-1/PD-L1 immunotherapy, while preventing the re-exhaustion of tumor-specific CD8(+) T cells.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
A. J. R. McGray, C. Eppolito, A. Miliotto, K. L. Singel, K. Stephenson, A. Lugade, B. H. Segal, T. Keler, G. Webster, B. Lichty, D. Kozbor, K. Odunsi
Summary: Cancer immunotherapies have shown significant clinical responses in some ovarian cancer patients, but there is still a need to identify combination therapies to overcome limitations of single-agent treatments. A study using a pre-clinical model of aggressive ovarian cancer found that a heterologous prime/boost cancer vaccine combined with checkpoint blockade improved tumor control, with a focus on the essential role of CD8 + T cells in tumor regression.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Oncology
Carlos Martinez-Gomez, Marie Michelas, Clara-Maria Scarlata, Anna Salvioni, Carlos Gomez-Roca, Victor Sarradin, Francoise Lauzeral-Vizcaino, Virginie Feliu, Agnes Dupret-Bories, Gwenael Ferron, Jerome Sarini, Christel Devaud, Jean-Pierre Delord, Camille-Charlotte Balanca, Alejandra Martinez, Maha Ayyoub
Summary: This study identified a population of CD4 T cells expressing inhibitory receptors targeted by immunotherapy in the blood of cancer patients. It showed that high proportions of these cells prior to therapy were associated with a response to immunotherapy. The study also found that exhausted CD4 T cells, which contained low proportions of effector cytokine-producing cells, may play a role in clinical responsiveness to immunotherapy.
Article
Oncology
Anna Morena D'Alise, Guido Leoni, Maria De Lucia, Francesca Langone, Linda Nocchi, Fabio Giovanni Tucci, Elisa Micarelli, Gabriella Cotugno, Fulvia Troise, Irene Garzia, Rosa Vitale, Veronica Bignone, Elena Di Matteo, Rosa Bartolomeo, Deborah H. Charych, Armin Lahm, Jonathan Zalevsky, Alfredo Nicosia, Elisa Scarselli
Summary: The addition of a third component to the combination of anti-PD-1 and vaccine led to complete eradication of large tumors and reduction of tumor-infiltrating regulatory T cells. These findings support the concept that integrating three steps of the cancer immunity cycle can achieve higher cure rates by expanding neoantigen-specific T cells, reversing exhausted T cell phenotype, and reducing intratumoral Tregs.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Immunology
Xin Lei, Jara Palomero, Iris de Rink, Tom de Wit, Martijn van Baalen, Yanling Xiao, Jannie Borst
Summary: This study reveals that Flagellin can recruit circulating M phi/OC progenitors into infected tissues through the TLR5 axis, which then stimulates these progenitors to differentiate locally into M phi s. This novel finding suggests that this pathway may enhance host protection against bacterial infection at mucosal sites, in addition to monocyte recruitment.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Glenn A. O. Cremers, Bas J. H. M. Rosier, Ab Meijs, Nicholas B. Tito, Sander M. J. van Duijnhoven, Hans van Eenennaam, Lorenzo Albertazzi, Tom F. A. de Greef
Summary: The study investigated the tunable design parameters of antibody-functionalized DNA nanostructures binding to therapeutically relevant receptors, revealing key insights into receptor binding efficiency governed mainly by nanostructure size and DNA handle location.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Immunology
Mark Mensink, Thi Ngoc Minh Tran, Esther A. Zaal, Ellen Schrama, Celia R. Berkers, Jannie Borst, Sander de Kivit
Summary: CD4(+) T cells play a role in immune responses depending on the environment and stage, with nutrient availability also impacting their functionality. TNFR2 has been identified as key in regulating T cells, particularly Tregs. This study provides new evidence for the role of TNFR2 in metabolic regulation.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Raquel S. Laureano, Jenny Sprooten, Isaure Vanmeerbeerk, Daniel M. Borras, Jannes Govaerts, Stefan Naulaerts, Zwi N. Berneman, Benoit Beuselinck, Kalijn F. Bol, Jannie Borst, An Coosemans, Angeliki Datsi, Jitka Faucikova, Lisa Kinget, Bart Neyns, Gerty Schreibelt, Evelien Smits, Rudiger Sorg, Radek Spisek, Kris Thielemans, Sandra Tuyaerts, Steven De Vleeschouwer, I. Jolanda M. de Vries, Yanling Xiao, Abhishek D. Garg
Summary: DC-based vaccination for cancer treatment has advanced significantly over recent decades, but still shows suboptimal anti-tumor efficacy in the clinic. Current efforts are focused on improving the immunogenicity and efficacy of DC vaccines in oncology.
Article
Oncology
Lars Guelen, Thierry O. Fischmann, Jerelyn Wong, Smita Mauze, Marco Guadagnoli, Nikolina Babala, Jozef Wagenaars, Veronica Juan, David Rosen, Winnie Prosise, Maurice Habraken, Imke Lodewijks, Danling Gu, Judith Stammen-Vogelzangs, Ying Yu, Jeanne Baker, David Lutje Hulsik, Lilian Driessen-Engels, Dan Malashock, Joost Kreijtz, Astrid Bertens, Evert de Vries, Astrid Bovens, Arne Bramer, Yiwei Zhang, Richard Wnek, Sean Troth, Elliot Chartash, Konstantin Dobrenkov, Svetlana Sadekova, Andrea van Elsas, Jason K. Cheung, Laurence Fayadat-Dilman, Jannie Borst, Amy M. Beebe, Hans Van Eenennaam
Summary: MK-5890, a novel CD27 agonistic antibody, has the potential to complement PD-1 checkpoint inhibition in cancer immunotherapy and is currently undergoing clinical evaluation.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biochemical Research Methods
Erik van Buijtenen, Wout Janssen, Paul Vink, Maurice J. M. Habraken, Laura J. A. Wingens, Andrea van Elsas, Wilhelm T. S. Huck, Jessie A. G. L. van Buggenum, Hans van Eenennaam
Summary: Researchers integrated multi-omics single-cell sequencing technologies with an in vitro differentiation method to analyze the phenotypic characteristics of individual cells, revealing differences in immunoglobulin subclass-specific surface markers, transcriptional profiles, and signaling transduction pathway components. They also identified differential expression and sensitivity to cytokine stimulation in different ASCs, highlighting the importance of SYK, NF-kappa B, and mTOR activity in plasma cell differentiation and IgG secretion. This multi-omics approach provides valuable insights into human ASCs in healthy and diseased samples, and offers a useful tool for identifying novel biomarkers and potential drug targets.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Multidisciplinary Sciences
Xin Lei, Indu Khatri, Tom de Wit, Iris de Rink, Marja Nieuwland, Ron Kerkhoven, Hans van Eenennaam, Chong Sun, Abhishek D. Garg, Jannie Borst, Yanling Xiao
Summary: Despite their low abundance, cDC1s play a crucial role in anti-cancer immunity and are positively associated with patient survival. This study demonstrates that contact with activated CD4(+) T-cells enables cDC1s to induce a CTL response. The transcriptomic signature of helped cDC1s correlates with tumor infiltration by CTLs, Thelper(h)-1 cells, and overall survival.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Mark Mensink, Ellen Schrama, Eloy Cuadrado, Derk Amsen, Sander de Kivit, Jannie Borst
Summary: This study finds that induced Treg cells in humans have distinct protein expression patterns compared to blood-derived inherent Treg and conventional T cells. While induced Treg cells share some signaling and metabolic proteins with inherent Treg cells, they are more similar to conventional T cells.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Arjan Kol, Xiaoyu Fan, Marta. A. A. Wazynska, Sander M. J. van Duijnhoven, Danique Giesen, Annechien Plat, Hans Van Eenennaam, Philip. H. H. Elsinga, Hans. W. W. Nijman, Marco de Bruyn
Summary: This study focuses on generating and radiolabeling monoclonal antibodies targeting human CD103 for non-invasive immune PET imaging, demonstrating their potential as biomarkers for effective anticancer immune responses. The results show high specificity and sensitivity of the CD103 immuno-PET tracers in visualizing T cell infiltration, indicating their suitability for future applications in cancer immunotherapy assessment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biochemical Research Methods
Tomasz Ahrends, Molly Weiner, Daniel Mucida
Summary: This article presents a method for physical separation of the mouse intestine, which can be used for subsequent flow cytometry and immunofluorescence analysis.