Review
Immunology
Jia-Tong Ding, Kang-Ping Yang, Hao-Nan Zhou, Ying-Feng Huang, Hui Li, Zhen Zong
Summary: CD8(+) T cells, a key component of the tumor immune system, enter a hyporeactive state in chronic inflammation, and understanding the mechanisms of T cell exhaustion is crucial for immunotherapeutic development. Transcription factors and epigenetic regulation may play a role in the heterogeneity and kinetics of CD8(+) T cell exhaustion, providing potential targets for immunotherapy. Gastrointestinal cancers show better anti-tumor T cell composition, indicating promising prospects for precision-targeted immunotherapy. This study focuses on the mechanisms and clinical applications of CD8(+) T cell exhaustion in gastrointestinal cancer, providing insights for future immunotherapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Zahra Mokhtari, Marzieh Rezaei, Mohammad Hossein Sanei, Amirreza Dehghanian, Zahra Faghih, Zahra Heidari, Shirin Tavana
Summary: This study investigated the prognostic value of CD8, CD3, PD-1, and Tim3 expression, as well as PD-1/Tim3 co-expression, in patients with colorectal cancer. The results showed that high expression of PD-1 in the invasive margin was associated with favorable clinicopathological characteristics and improved overall survival in a subgroup of patients with high CD8 expression. High Tim3 expression in the tumor center was associated with advanced M-stage and decreased overall survival. PD-1 and Tim3 co-expression did not synergistically predict overall survival.
FRONTIERS IN ONCOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Jihye Hong, Mikyung Kang, Mungyo Jung, Yun Young Lee, Yongbum Cho, Cheesue Kim, Seuk Young Song, Chun Gwon Park, Junsang Doh, Byung-Soo Kim
Summary: While T-cell therapy is a significant breakthrough in cancer immunotherapy, its efficacy against solid tumors is limited due to T-cell exhaustion caused by immunosuppressive mechanisms. T-cell-derived nanovesicles (TCNVs) produced by extrusion through membranes with micro/nanosized pores show promising anti-tumoral activity in the immunosuppressive tumor microenvironment. TCNVs express programmed cell death protein 1 and TGF-beta receptor on their surface, which helps block PD-L1 on cancer cells and scavenge TGF-beta in the TME, preventing T-cell exhaustion and directly killing cancer cells. These findings suggest TCNVs as an effective strategy for cancer immunotherapy to overcome tumor's immunosuppressive mechanisms.
ADVANCED MATERIALS
(2021)
Review
Immunology
Jannie Borst, Julia Busselaar, Douwe M. T. Bosma, Ferry Ossendorp
Summary: The article explains the importance of the PD-1 checkpoint in cancer treatment by outlining how it regulates the CD8(+) T cell response. It also discusses the role of PD-1 during T cell priming and emphasizes the importance of CD4(+) T cell help in optimizing CTL efficacy.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Christiane S. Eberhardt, Haydn T. Kissick, Mihir R. Patel, Maria A. Cardenas, Nataliya Prokhnevska, Rebecca C. Obeng, Tahseen H. Nasti, Christopher C. Griffith, Se Jin Im, Xu Wang, Dong M. Shin, Mary Carrington, Zhuo G. Chen, John Sidney, Alessandro Sette, Nabil F. Saba, Andreas Wieland, Rafi Ahmed
Summary: The study identified different transcriptional subsets of HPV-specific CD8 T cells in HPV-positive head and neck cancer, highlighting the potential response to PD-1 blockade. Furthermore, the inclusion of E2 and E5 proteins in HPV therapeutic vaccines should be considered to elicit a broader tumor-reactive CD8 T cell response.
Article
Chemistry, Multidisciplinary
Weijing Yang, Meng Zhang, Jinjie Zhang, Yanlong Liu, Jie Ning, Jing Yang, Zhenzhong Zhang, Lin Hou, Xiaoyuan Chen
Summary: Targeting pre-activated T cells with immune checkpoint blockade through sequential therapy enhances immune response and improves antitumor activity.
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
Oncology
Yiming Li, Juan Tang, Jianli Jiang, Zhinan Chen
Summary: Immunotherapy has achieved significant success in treating cancer, but resistance to this treatment often occurs due to the complex metabolic networks in the tumor microenvironment. Metabolic checkpoints play a crucial role in regulating T cell development, differentiation, and function, as well as coordinating metabolic competition between tumor cells and infiltrating T cells. Thus, targeting metabolic checkpoints may enhance the efficacy of immunotherapy.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Review
Cell Biology
Di Chen, Yinglu Guo, Jiahuan Jiang, Pin Wu, Ting Zhang, Qichun Wei, Jian Huang, Dang Wu
Summary: Reviewing the characteristics, heterogeneity, and mechanisms of gamma delta T cell exhaustion provides insights into the combined strategies to enhance gamma delta T cell-based antitumor immunotherapy.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Chemistry, Physical
Tianyuan Xue, Zhirang Zhang, Tianliang Fang, Baoqi Li, Yuan Li, Liyan Li, Yanghua Jiang, Fangfang Duan, Fanqiang Meng, Xin Liang, Xudong Zhang
Summary: In this study, cellular vesicles displaying anti-PD-1 single-chain variable fragment antibody and A(2a) adenosine receptor antagonist CPI-444 were prepared to reinvigorate T cell immunity and enhance anti-tumor activation.
Article
Oncology
Juan A. Hernandez-Aceves, Jacquelynne Cervantes-Torres, Diana Torres-Garcia, Francisco J. Zuniga-Flores, Osiris J. Patino-Chavez, Jorge A. Pena Agudelo, Jose Eduardo Aguayo-Flores, Yonathan Garfias, Laura Montero-Leon, Laura Romero-Romero, Armando Perez-Torres, Gladis Fragoso, Edda Sciutto
Summary: GK-1 has shown anti-tumor and anti-metastatic effects in an experimental model of breast cancer. It can decrease tumor growth, lung and lymph node metastases, and intra-tumor vascular areas. Furthermore, GK-1 prevents T cell exhaustion, enhances cytotoxic activity, and improves the prognosis of triple-negative breast cancer.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Immunology
Valerie Janelle, Mathieu Neault, Marie-Eve Lebel, Dave Maurice De Sousa, Salix Boulet, Ludovic Durrieu, Cedric Carli, Chloe Muzac, Sebastien Lemieux, Nathalie Labrecque, Heather J. J. Melichar, Frederick A. Mallette, Jean-Sebastien Delisle
Summary: The development of T-cell dysfunction upon repeated antigen exposure involves the accumulation of DNA damage and activation of the p38MAPK signaling pathway, leading to cellular senescence features including p16(INK4a) upregulation. However, targeting p16(INK4a) can improve T-cell functionality in exhausted CAR T cells, suggesting T-cell senescence as a potential target in immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Ines Ruedas-Torres, Irene M. Rodriguez-Gomez, Jose Maria Sanchez-Carvajal, Silvia Guil-Luna, Fernanda Larenas-Munoz, Francisco J. Pallares, Librado Carrasco, Jaime Gomez-Laguna
Summary: This study aimed to evaluate the expression of selected immune checkpoints in the thymus of piglets infected with two different PRRSV-1 strains. The up-regulation of PD1/PDL1, CTLA4, TIM3, LAG3 and IDO1 immune checkpoints in the thymus of PRRSV-infected piglets, especially those infected with the virulent Lena strain from 6 dpi onwards, was associated with disease progression, high viral load and cell death. Co-expression of these molecules can negatively regulate the host immune response against PRRSV by affecting T-cell development, maturation and selection.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Debayan Mukherjee, Erminia Romano, Richard Walshaw, Leo A. H. Zeef, Antonia Banyard, Stephen J. Kitcatt, Eleanor J. Cheadle, Karoliina Tuomela, Swati Pendharkar, Aws Al-Deka, Beatrice Salerno, Sophie Raby, Ian G. Mills, Jamie Honeychurch, Tim M. Illidge
Summary: Despite advances in immune checkpoint inhibitors (ICI), many tumors still exhibit resistance and fail to respond to treatment. The combination of radiation therapy (RT) and ICI has not shown promising results in clinical trials. Therefore, novel approaches are needed to overcome this resistance and improve clinical outcomes.
Article
Pharmacology & Pharmacy
Katarzyna Magiera-Mularz, Katarzyna Kuska, Lukasz Skalniak, Przemyslaw Grudnik, Bogdan Musielak, Jacek Plewka, Justyna Kocik, Malgorzata Stec, Kazimierz Weglarczyk, Dominik Sala, Benedykt Wladyka, Maciej Siedlar, Tad A. Holak, Grzegorz Dubin
Summary: The study reports a macrocyclic peptide p101 capable of blocking the PD-L1/PD-1 immune checkpoint, showing that the interaction is primarily guided by hydrophobic forces. Experimental results demonstrate that p101 can effectively inhibit the interaction between PD-L1 and PD-1 in the cellular environment, releasing the immune response of human T cells.
ADVANCED THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Anais Boisson, Gregory Noel, Manuel Saiselet, Joel Rodrigues-Vitoria, Noemie Thomas, Mireille Langouo Fontsa, Doina Sofronii, Celine Naveaux, Hugues Duvillier, Ligia Craciun, Denis Larsimont, Ahmad Awada, Vincent Detours, Karen Willard-Gallo, Soizic Garaud
Summary: Understanding the interactions between tumor cells and their microenvironment has led to advancements in cancer treatments, particularly in the development of immunotherapies. Immunotherapies rely on immune cells in the tumor microenvironment to influence treatment responses. Advanced technologies like flow cytometry and spatial transcriptomics are increasingly used in translational research to study the complexity of the tumor immune microenvironment.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Oncology
Rafael Caparica, Marco Bruzzone, Elisa Agostinetto, Maria Alice Franzoi, Marcello Ceppi, Nina Radosevic-Robin, Frederique Penault-Llorca, Karen Willard-Gallo, Sherene Loi, Roberto Salgado, Evandro de Azambuja
Summary: High-TIL levels in non-invasive breast cancer are associated with an increased likelihood of local recurrence, but a decreased likelihood of invasive local recurrence. They are also associated with aggressive tumor subtypes, high grade, and necrosis.
Editorial Material
Oncology
Victor Engelhard, Jose Conejo-Garcia, Rafi Ahmed, Brad Nelson, Karen Willard-Gallo, Tullia Bruno, Wolf Fridman
Summary: Tumor-infiltrating B cells work alongside T cells to combat tumors, controlling tumor growth through various mechanisms and showing a correlation with immunotherapy response.
Article
Oncology
Julia Katharina Schwarze, Soizic Garaud, Yanina J. L. Jansen, Gil Awada, Valerie Vandersleyen, Jens Tijtgat, Alexandre de Wind, Paulus Kristanto, Teofila Seremet, Karen Willard-Gallo, Bart Neyns
Summary: Low-dose regimens of PD-1 immune checkpoint inhibitors may serve as effective and cost-efficient alternatives to standard dosing in melanoma patients. Immunohistochemical tumor profiling shows promise as a potential biomarker.
Article
Oncology
Yvonne Wesseling-Rozendaal, Arie van Doorn, Karen Willard-Gallo, Anja van de Stolpe
Summary: Immunotherapy is a potential cure for cancer, but only a small number of breast cancer patients benefit from it. CD4+ T cells play a role in the immune response and resistance to immunotherapy. Researchers have developed a new technology to measure the activity of signal transduction pathways in these cells and found abnormal function of CD4+ T cells in breast cancer patients. The abnormal activity suggests that CD4+ T cells have transformed into regulatory T cells, which inhibit the immune response and are associated with resistance to immunotherapy. This new technology can be used to identify patients who will benefit from immunotherapy.
Article
Medicine, General & Internal
Karim Gourari, Julien Catherine, Soizic Garaud, Joseph Kerger, Antonia Lepida, Aspasia Georgala, Fabienne Lebrun, Maria Gomez Galdon, Thierry Gil, Karen Willard-Gallo, Mireille Langouo Fontsa
Summary: The combination therapy of TKIs and ICIs in advanced ccRCC can result in high-grade toxicities, including vanishing bile duct syndrome. Immunological studies suggest the potential role of T-cells in the pathogenesis of the disease.
Article
Hematology
Paola Circosta, Chiara Donini, Susanna Gallo, Lidia Giraudo, Loretta Gammaitoni, Ramona Rotolo, Federica Galvagno, Sonia Capellero, Marco Basirico, Monica Casucci, Massimo Aglietta, Ivana Ferrero, Franca Fagioli, Alessandro Cignetti, Fabrizio Carnevale-Schianca, Valeria Leuci, Dario Sangiolo
Summary: This study explored the feasibility, anti-leukaemic activity, and alloreactive risk of genetically redirected CIK (fcCAR.CIK) generated from full-donor chimaeric patients. The results showed that fcCAR.CIK exhibited intense preclinical anti-leukaemic activity without enhancing the risk of graft-versus-host disease, supporting the potential use of fcCAR.CIK as an alternative to conventional donor lymphocyte infusion following haematopoietic cell transplantation.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Ramona Rotolo, Valeria Leuci, Chiara Donini, Federica Galvagno, Annamaria Massa, Maria Chiara De Santis, Serena Peirone, Giovanni Medico, Martina Sanlorenzo, Igor Vujic, Loretta Gammaitoni, Marco Basirico, Luisella Righi, Chiara Riganti, Iris Chiara Salaroglio, Francesca Napoli, Fabrizio Tabbo, Annapaola Mariniello, Elisa Vigna, Chiara Modica, Lorenzo D'Ambrosio, Giovanni Grignani, Riccardo Taulli, Emilio Hirsch, Matteo Cereda, Massimo Aglietta, Giorgio Vittorio Scagliotti, Silvia Novello, Paolo Bironzo, Dario Sangiolo
Summary: This study reports a novel therapeutic activity of anti-PD-1 antibodies against non-small cell lung cancer (NSCLC), which can block the tumor-intrinsic PD-1 receptors on chemoresistant cells. PD-1 expression in NSCLC cells was found to increase after cisplatin treatment, and anti-PD-1 antibodies can inhibit the recovery of chemo-surviving cells. The study suggests that anti-PD-1 antibodies have a lymphocyte-independent activity in NSCLC and can be used to prevent disease relapses after chemotherapy.
CLINICAL CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Erika Fiorino, Alessandra Merlini, Lorenzo D'Ambrosio, Ilaria Cerviere, Enrico Berrino, Caterina Marchio, Lidia Giraudo, Marco Basirico, Annamaria Massa, Chiara Donini, Valeria Leuci, Ramona Rotolo, Federica Galvagno, Letizia Vitali, Alessia Proment, Soldano Ferrone, Alberto Pisacane, Ymera Pignochino, Massimo Aglietta, Giovanni Grignani, Giulia Mesiano, Dario Sangiolo
Summary: This study investigates the immunotherapy efficacy on imatinib and sunitinib-resistant wild-type gastrointestinal stromal tumors (wtGIST) using a patient-derived preclinical model. The results show that cytokine-induced killer lymphocytes (CIK) can kill resistant wtGIST cells, and interferons (IFN) have anti-tumor effects on certain resistant wtGIST cells. These findings support the exploration of CIK immunotherapy in clinical studies and the reevaluation of IFN within this challenging setting.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Cristina Chiriaco, Chiara Donini, Marco Cortese, Stefano Ughetto, Chiara Modica, Ilaria Martinelli, Alessia Proment, Letizia Vitali, Lara Fontani, Monica Casucci, Paolo Maria Comoglio, Silvia Giordano, Dario Sangiolo, Valeria Leuci, Elisa Vigna
Summary: The study proposes an immunotherapy strategy using CAR-T lymphocytes targeting MET overexpressing tumors across different histotypes, showing specific cytotoxic activity and potential to overcome acquired resistance to MET targeting agents in cancer cells. The approach holds promise for cancers not responsive to traditional MET inhibition therapies.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Cell Biology
Annapaola Mariniello, Fabrizio Tabbo, Davide Indellicati, Martina Tesauro, Nicole Alessia Rezmives, Maria Lucia Reale, Angela Listi, Enrica Capelletto, Simona Carnio, Valentina Bertaglia, Caterina Mecca, Lorena Consito, Marco De Filippis, Maristella Bungaro, Chiara Paratore, Massimo Di Maio, Francesco Passiglia, Luisella Righi, Dario Sangiolo, Silvia Novello, Massimo Geuna, Paolo Bironzo
Summary: This study explored and compared T cell characteristics in broncho-alveolar lavage (BAL) from tumor affected and contralateral lung, as well as matched peripheral blood (PB), in lung cancer patients. The results showed that T cells in BAL from advanced lung cancer patients presented features of exhaustion, which could be potential biomarkers for cancer immunotherapy outcome.
Article
Oncology
Alessandra Merlini, Maria Laura Centomo, Giulio Ferrero, Giulia Chiabotto, Umberto Miglio, Enrico Berrino, Giorgia Giordano, Silvia Brusco, Alberto Pisacane, Elena Maldi, Ivana Sarotto, Federica Capozzi, Cristina Lano, Claudio Isella, Giovanni Crisafulli, Massimo Aglietta, Angelo Paolo Dei Tos, Marta Sbaraglia, Dario Sangiolo, Lorenzo D'Ambrosio, Alberto Bardelli, Ymera Pignochino, Giovanni Grignani
Summary: The study identified an 8-gene expression signature to improve prediction of response to the trabectedin+olaparib combination in BSTS patients. The predictive role of these potential biomarkers warrants further investigation.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Letizia Vitali, Alessandra Merlini, Federica Galvagno, Alessia Proment, Dario Sangiolo
Summary: The outbreak of COVID-19 has disproportionately affected cancer patients, and there are unexpected immunobiological connections between SARS-CoV-2 infection and cancer. Numerous studies have explored the interconnections between COVID-19 and cancer, focusing on various aspects including psychological implications and prognostic factors. This review discusses the dynamic behavior of cytokines and immune signaling pathways in both acute and chronic stages of SARS-CoV-2 infection and cancer, highlighting the biological similarities and potential therapeutic opportunities.
Article
Biotechnology & Applied Microbiology
Ilenia Iaia, Virginia Brancato, David Caballero, Rui L. Reis, Massimo Aglietta, Dario Sangiolo, Subhas C. Kundu
Summary: Little is known about the role of fibroblasts in solid tumors such as melanoma and the mechanism behind it due to the lack of relevant pre-clinical models. In this report, a melanoma-on-a-chip model was proposed to evaluate the essential role of fibroblasts in the antitumor activity of lymphocytes. The presence of fibroblasts was observed to inhibit immune effector recruitment in a 3D pre-clinical tumor model.
BIOENGINEERING-BASEL
(2023)
Article
Oncology
Valentina Tuninetti, Eleonora Ghisoni, Sandro Pignata, Elisa Picardo, Francesco Raspagliesi, Claudia Andreetta, Elena Maldi, Grazia Artioli, Serafina Mammoliti, Lucia Zanchi, Angelica Sikokis, Nicoletta Biglia, Alessandro Parisi, Vincenzo Dario Mandato, Claudia Carella, Gennaro Cormio, Marco Marinaccio, Andrea Puppo, Biagio Paolini, Lucia Borsotti, Giulia Scotto, Margherita Turinetto, Dario Sangiolo, Massimo Di Maio, Giorgio Valabrega
Summary: The expression of Ki67 at diagnosis does not predict the response to PARP inhibitors in BRCA wild-type ovarian cancer patients.
