Review
Immunology
Timothy N. J. Bullock
Summary: Advances in checkpoint blockade immunotherapies have led to an expansion in methods for promoting T cell access to the tumor microenvironment, with dendritic cells playing a crucial role in the immune response to tumor antigens. The role of CD40 as a master regulator of dendritic cell activation in cancer vaccines and other immune-oncology approaches is highlighted and evaluated.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Shimpei Maruoka, Toshiyasu Ojima, Hiromitsu Iwamoto, Junya Kitadani, Hirotaka Tabata, Shinta Tominaga, Masahiro Katsuda, Keiji Hayata, Akihiro Takeuchi, Hiroki Yamaue
Summary: This study demonstrates the successful generation of DC vaccines with potent anti-tumor effects using induced pluripotent stem cells (iPSCs) transfected with ivtRNA derived from colorectal cancer patients. The study also identified potential neoantigens and showed the ability of the generated DC vaccines to induce cytotoxic T lymphocytes (CTLs) against these neoantigens.
SCIENTIFIC REPORTS
(2022)
Article
Immunology
David A. Bernal-Estevez, Mauren A. Ortiz Barbosa, Paola Ortiz-Montero, Claudia Cifuentes, Ramiro Sanchez, Carlos A. Parra-Lopez
Summary: This study investigates the safety and immunogenicity of autologous antigen-free DCs administered to breast cancer patients (BCPs) in combination with NAC-AC. The results suggest that the administration of DCs in combination with NAC-AC enhances the functional capacity of T cells in BCPs, potentially potentiating the adjuvant effect of ICD induced by NAC-AC on T cells and increasing the immunogenicity of tumors as cryptic vaccines.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Sarah I. M. Sutherland, Xinsheng Ju, L. G. Horvath, Georgina J. Clark
Summary: Despite the success of using checkpoint inhibitors to reprim T cells to recognize tumors in certain malignancies, including melanoma, lung, and renal cell carcinoma, many tumors, such as prostate cancer, remain resistant to such treatment. DC-based immunotherapy, such as Sipuleucel-T, has shown improved overall survival in prostate cancer, but further research into DC vaccines has been limited. Understanding the immunosuppressive environment of prostate cancer and developing new vaccine strategies that can overcome this environment is essential for future success in immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Sahil Inamdar, Abhirami P. Suresh, Joslyn L. Mangal, Nathan D. Ng, Alison Sundem, Hoda Shokrollahzadeh Behbahani, Thomas E. Rubino Jr, Xiaojian Shi, Sharon T. Loa, Jordan R. Yaron, Taro Hitosugi, Matthew Green, Haiwei Gu, Marion Curtis, Abhinav P. Acharya
Summary: Using biomaterials to deliver succinate metabolite to immune cells activates them and modulates their metabolism, which has potential applications in cancer immunotherapies.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Oncology
Yue Liu, Joanna Pagacz, Donald J. Wolfgeher, Kenneth D. Bromerg, Jacob Gorman, Stephen J. Kron
Summary: Antigen presentation may be the limiting factor in the low immune response to radiation therapy, and combining immune checkpoint blockade does not restore cytotoxic T lymphocytes function. Therapeutic vaccines based on senescent tumor cells or SnC-activated dendritic cells have the potential to enhance immune therapies and limit recurrence or metastasis.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Nanoscience & Nanotechnology
Chao Liu, Xue Liu, Xinchu Xiang, Xin Pang, Siyuan Chen, Yunming Zhang, En Ren, Lili Zhang, Xuan Liu, Peng Lv, Xiaoyong Wang, Wenxin Luo, Ningshao Xia, Xiaoyuan Chen, Gang Liu
Summary: This study presents a genetically engineered cell membrane nanovesicle for cancer immunotherapy. The nanovaccine, named ASPIRE, can improve antigen delivery to lymphoid organs and generate broad-spectrum T-cell responses that eliminate established tumors. This work provides a powerful vaccine formula that can directly activate both native T cells and exhausted T cells, suggesting a general strategy for personalized cancer immunotherapy.
NATURE NANOTECHNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Yunkai Yang, Xiaohan Guo, Bo Hu, Peng He, Xiaowu Jiang, Zuohuan Wang, Huaxing Zhu, Lina Hu, Minghua Yu, Meiqing Feng
Summary: The fusion protein SNU containing SecPen and ubiquitin-fused NY-ESO-1 loaded onto dendritic cells can elicit stronger and specific T cell immune responses, resulting in increased cytotoxicity towards MC38(NY-ESO-1) tumor cells.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Chemistry, Multidisciplinary
Seokhyeong Go, Mungyo Jung, Suyoung Lee, Sangjun Moon, Jihye Hong, Cheesue Kim, Yeonseok Chung, Byung-Soo Kim
Summary: A therapeutic cancer nanovaccine has been developed that enhances T cell responses by interacting with both dendritic cells (DCs) and T cells. This nanovaccine, named CCM-MPLA-aCD28, activates tumor-specific CD8+ T cells and exhibits a higher antitumor efficacy compared to nanovaccines that interact with either DCs or T cells.
ADVANCED MATERIALS
(2023)
Article
Oncology
Shu Yazaki, Tatsuya Yoshida, Yuki Kojima, Shigehiro Yagishita, Hiroko Nakahama, Keiji Okinaka, Hiromichi Matsushita, Mika Shiotsuka, Osamu Kobayashi, Satoshi Iwata, Yoshitaka Narita, Akihiro Ohba, Masamichi Takahashi, Satoru Iwasa, Kenya Kobayashi, Yuichiro Ohe, Tomokazu Yoshida, Akinobu Hamada, Toshihiko Doi, Noboru Yamamoto
Summary: This study evaluated the serum SARS-CoV-2 antibody status in cancer patients and healthcare workers in Japan during the COVID-19 pandemic. The seroprevalence did not differ significantly between the two groups, but it was found that cancer comorbidity and treatment with chemotherapy and immune checkpoint inhibitors may impact the immune response to SARS-CoV-2.
Article
Oncology
Antonella Brunello, Valentina Guarneri, Marina Coppola, Matteo Bernardi, Ketti Ottolitri, Maria Grazia Ghi, Eleonora Mioranza, Federica Vianello, Michele Gottardi, Sara Lonardi, Vittorina Zagonel
Summary: This study analyzes adverse events in 5297 cancer patients undergoing anti-cancer treatment who were vaccinated with the Pfizer-BioNTech COVID-19 vaccine. The results show that 8 adverse drug reactions were reported, with one being severe and seven being non-severe. The non-severe reactions resolved within 48 hours. This is the largest study to date on the safety of vaccination in cancer patients.
Article
Immunology
Justin Theophilus Ulrich-Lewis, Kevin E. Draves, Kelsey Roe, Megan A. O'Connor, Edward A. Clark, Deborah Heydenburg Fuller
Summary: This study found that stimulator of interferon genes (STING) plays a critical role within conventional dendritic cells (cDCs) in mediating adaptive immune responses induced by DNA vaccines. STING within cDCs was shown to be responsible for the induction of type I T helper cell responses and Th1-type antibody responses, as well as the development of CD8(+) effector cell responses. These findings provide new insight into the mechanism of DNA vaccine-induced immune responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Adnan Deronic, Anneli Nilsson, Mia Thagesson, Doreen Werchau, Karin Enell Smith, Peter Ellmark
Summary: Mitazalimab, a human anti-CD40 agonist antibody, was found to activate antigen-presenting cells, leading to expansion and activation of antigen-specific T cells, ultimately enhancing the anti-tumor efficacy of a model cancer vaccine.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Oncology
S. P. Lau, L. Klaase, M. Vink, J. Dumas, K. Bezemer, A. van Krimpen, R. van der Breggen, L. V. Wismans, M. Doukas, W. de Koning, A. P. Stubbs, D. A. M. Mustafa, H. Vroman, R. Stadhouders, J. B. Nunes, C. Stingl, N. F. C. C. de Miranda, T. M. Luider, S. H. van der Burg, J. G. Aerts, C. H. J. van Eijck
Summary: This study demonstrates the feasibility and safety of using allogeneic lysated dendritic cell vaccine in patients with resected pancreatic ductal adenocarcinoma. The vaccine induces immune reactivity to PDAC expressed antigens and has the potential to prevent disease recurrence and progression.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Oncology
Takayoshi Yamauchi, Toshifumi Hoki, Takaaki Oba, Ryutaro Kajihara, Kristopher Attwood, Xuefang Cao, Fumito Ito
Summary: The use of tumor mutation-derived neoantigens in cancer vaccines shows promise, but overall clinical efficacy is limited. The frequency of circulating CX3CR1(+) CD8(+) T cells and specific signaling molecules are correlated with the antitumor efficacy of neoantigen vaccines. While the CX3CR1(+) subset may not be essential for antitumor CD8(+) T cell responses, it can serve as a predictive T-cell biomarker for effective priming of CD8(+) T cells.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Oncology
Koen A. Marijt, Lisa Griffioen, Laura Blijleven, Sjoerd. H. van der Burg, Thorbald van Hall
Summary: TEIPP is a novel category of cancer antigens that emerge on cancers with functional loss of peptide pump TAP, evoking CD8 T cell immune response. By studying LRPAP1(21-30)-specific CD8 T cells, it was found that replacing the serine anchor with valine in the signal sequence enhances HLA-A2 binding affinity and T cell stimulation.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Oncology
Chantal L. Duurland, Saskia J. Santegoets, Ziena Abdulrahman, Nikki M. Loof, Gregor Sturm, Tom H. Wesselink, Ramon Arens, Sanne Boekestijn, Ilina Ehsan, Mariette I. E. van Poelgeest, Francesca Finotello, Hubert Hackl, Zlatko Trajanoski, Peter Ten Dijke, Veronique M. Braud, Marij J. P. Welters, Sjoerd H. van der Burg
Summary: The expression of CD4+CD161+ effector memory T cells is associated with improved survival in HPV16+ oropharyngeal squamous cell carcinoma. Therapeutic vaccination activates and expands CD4+CD161+ effector T cells. CD161 functions dynamically and is regulated by cell intrinsic and extrinsic factors. CD161 expressing CD4+ T cells respond more vigorously to suboptimal antigen stimulation and may amplify TCR signals.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Editorial Material
Immunology
Rebeca Alonso-Arias, Ramon Arens, Marco A. Moro-Garcia
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Nadia de Gruil, Hanno Pijl, Sjoerd H. van der Burg, Judith R. Kroep
Summary: Stimulating our body's immune response through short-term fasting diets can enhance the efficacy of cancer therapy, particularly chemotherapy. This review summarizes the preclinical and clinical evidence supporting the synergistic effects of fasting diets with cancer therapy by boosting antitumor immunity. The potential mechanisms underlying these effects include enhanced tumor immunity, decreased growth signaling, and alleviation of immunosuppression. Further studies are needed to fully evaluate the benefits of combining short-term fasting with not only chemotherapy, but also immunotherapy in cancer treatment.
Article
Oncology
Floris Dammeijer, Mandy van Gulijk, Larissa Klaase, Menno van Nimwegen, Rachid Bouzid, Robin Hoogenboom, Maria E. Joosse, Rudi W. Hendriks, Thorbald van Hall, Joachim G. Aerts
Summary: Chronic IL2 receptor (IL2R)-STAT5 pathway signaling has been identified as a key driver of T-cell exhaustion, with JAK3 inhibition showing promising effects in improving T-cell responses and reducing tumor load. JAK3 represents a novel and promising target for combination immunotherapy.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Multidisciplinary Sciences
Iris N. Pardieck, Tetje C. van der Sluis, Esme T. van der Gracht, Dominique M. B. Veerkamp, Felix M. Behr, Suzanne van Duikeren, Guillaume Beyrend, Jasper Rip, Reza Nadafi, Elham Beyranvand Nejad, Nils Mulling, Dena J. Brasem, Marcel G. M. Camps, Sebenzile K. Myeni, Peter J. Bredenbeek, Marjolein Kikkert, Yeonsu Kim, Luka Cicin-Sain, Tamim Abdelaal, Klaas P. J. M. van Gisbergen, Kees L. M. C. Franken, Jan Wouter Drijfhout, Cornelis J. M. Melief, Gerben C. M. Zondag, Ferry Ossendorp, Ramon Arens
Summary: Repeated booster vaccinations with a three dose regimen of a synthetic peptide vaccine significantly enhance the CD8(+) T cell response, leading to protection against lethal SARS-CoV-2 infection. Understanding the mechanisms and impact of booster vaccinations is crucial for vaccine design and delivery.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Leonard R. Pelgrom, Thiago A. Patente, Frank Otto, Lonneke V. Nouwen, Arifa Ozir-Fazalalikhan, Alwin J. van der Ham, Hendrik J. P. van der Zande, Graham A. Heieis, Ramon Arens, Bart Everts
Summary: This study reveals that mTORC1 limits the activation of CD8(+) T cells in vivo by regulating the metabolism and immunogenicity of different subsets of antigen-presenting cells, but it does not affect antigen-specific CD8(+) T cell responses to infection.
Article
Immunology
Ruud H. Wijdeven, Birol Cabukusta, Felix M. Behr, Xueer Qiu, Deeba Amiri, Daniel M. Borras, Ramon Arens, Yun Liang, Jacques Neefjes
Summary: The PD-L1/2-PD-1 immune checkpoint is crucial for maintaining peripheral tolerance and preventing autoimmunity, but tumor cells can exploit it for immune evasion. This study identified three factors, GATA2, MBD6, and VGLL3, that upregulate PD-L1 expression. VGLL3 acts as a transcriptional regulator and, in conjunction with TEAD1 and RUNXI/3, drives the expression of PD-L1/2. This work reveals a new transcriptional complex controlling PD-L1/2 expression and suggests that VGLL3 can balance inflammation by upregulating the anti-inflammatory factors PD-L1 and PD-L2.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Oncology
Toon Stegmann, Anna-Sophia Wiekmeijer, Kitty Kwappenberg, Suzanne van Duikeren, Farien Bhoelan, Denzel Bemelman, Thomas J. M. Beenakker, Willem-Jan Krebber, Ramon Arens, Cornelis J. M. Melief
Summary: Therapeutic cancer vaccines can activate CD4+ and CD8+ T cells to eradicate tumors. Different platforms such as DNA, mRNA, and synthetic long peptide (SLP) vaccines have been used to induce robust T cell responses. In this study, virosomes, nanoparticles made from influenza virus membranes, were utilized as a delivery vehicle for SLPs. Virosomes loaded with Amplivant-conjugated SLPs showed superior expansion of antigen-specific CD8+ T memory cells in ex vivo experiments with human PBMCs.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Oncology
Marit J. van Elsas, Camilla Labrie, Anders Etzerodt, Pornpimol Charoentong, Jordi J. C. van Stigt Thans, Thorbald Van Hall, Sjoerd H. van der Burg
Summary: A small population of CD163(hi) tissue-resident macrophages is identified to be responsible for primary and secondary resistance against T-cell-based immunotherapies. While these CD163(hi) M2 macrophages are resistant to Csf1r-targeted therapies, in-depth characterization and identification of the underlying mechanisms driving immunotherapy resistance allows the specific targeting of this subset of macrophages, thereby creating new opportunities for therapeutic intervention with the aim to overcome immunotherapy resistance.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
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
Gerwin Gerhard Wemke Sandker, Jim Middelburg, Evienne Wilbrink, Janneke Molkenboer-Kuenen, Erik Aarntzen, Thorbald van Hall, Sandra Heskamp
Summary: CD3xTRP1 efficiently targets TRP1-positive tumors and CD3-rich tissues primarily through receptor-mediated targeting. Rapid receptor-mediated internalization of CD3xTRP1 in TRP1-positive tumors and CD3-rich tissues was demonstrated. Despite the decreased available dose, CD3xTRP1 still induced effective antitumor T-cell responses and inhibited tumor growth. Our findings provide a basis for further optimization of CD3-bsAb therapies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Medicine, Research & Experimental
Jeroen van Bergen, Marcel G. M. Camps, Iris N. Pardieck, Dominique Veerkamp, Wing Yan Leung, Anouk A. Leijs, Sebenzile K. Myeni, Marjolein Kikkert, Ramon Arens, Gerben C. Zondag, Ferry Ossendorp
Summary: SARS-CoV-2 is the third zoonotic coronavirus to cause a major outbreak in humans in recent years, and there are other SARS-like coronaviruses with pandemic potential circulating in animals. T cell-based pan-sarbecovirus vaccines have been designed and preclinically tested, which can protect against hospitalization and death caused by these viruses by inducing T cell immunity.
Editorial Material
Biochemical Research Methods
J. Frederique Graaf, Ramon Arens
Summary: A high-throughput and accurate single-cell immunophenotyping pipeline has been developed to decipher the immune system's responses to drug screening and immunotherapy.
CELL REPORTS METHODS
(2023)