Article
Oncology
Devayani Machiraju, Melanie Wiecken, Nina Lang, Ingrid Huelsmeyer, Jasmin Roth, Timo E. Schank, Rosa Eurich, Niels Halama, Alexander Enk, Jessica C. Hassel
Summary: Different mechanisms lead to resistance to immune checkpoint inhibitors in melanoma patients. Soluble immune checkpoints and T cell expression were analyzed, showing associations between certain markers and resistance to specific treatments, with potential implications for clinical use.
Review
Oncology
Maria de Miguel, Pablo Umana, Ana Luiza Gomes de Morais, Victor Moreno, Emiliano Calvo
Summary: T-cell engagers (TCE) are a novel group of treatments that simultaneously engage T-cell surface molecules and tumoral cell antigens. Success has been observed in hematologic field but not yet in solid tumors due to their biological complexity. Research is ongoing to improve solid tumors therapeutics through different strategies.
CLINICAL CANCER RESEARCH
(2021)
Review
Biology
Arnaud Del Bello, Emmanuel Treiner
Summary: Manipulating immune checkpoints could potentially lead to a state of specific hypo-responsiveness towards grafted organs, reducing the need for immunosuppressive medications and their associated toxicities.
Review
Immunology
Alain E. Andrea, Andrada Chiron, Sarah Mallah, Stephanie Bessoles, Guillaume Sarrabayrouse, Salima Hacein-Bey-Abina
Summary: CAR-T cell therapy has limited efficacy in solid tumors due to the immunosuppressive tumor microenvironment. To overcome this obstacle, researchers are designing new CAR-T cell engineering strategies to enhance the anti-cancer activity of CAR-T cells in hostile environments.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Maria Hinterberger, Raphael Giessel, Giovanna Fiore, Fabienne Graebnitz, Barbara Bathke, Sonia Wennier, Paul Chaplin, Ignacio Melero, Mark Suter, Henning Lauterbach, Pedro Berraondo, Hubertus Hochrein, Jose Medina-Echeverz
Summary: Intratumoral virotherapy with MVA-TAA-4-1BBL led to control of established tumors, triggering proinflammatory changes and immunogenic cell death in the tumor microenvironment. This approach induced reactivation and expansion of potent tumor-specific CD8(+) T cells, resulting in tumor elimination and protective immunological memory against tumor rechallenge.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(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.
Review
Pharmacology & Pharmacy
Claire O. Kisamore, Brittany D. Elliott, A. Courtney Devries, Randy J. Nelson, William H. Walker II
Summary: Circadian rhythms are internal manifestations of the 24-h solar day that synchronize biological and behavioral processes to improve adaptive function and survival. Chronotherapy optimizes drug administration based on circadian rhythms to achieve maximum therapeutic efficacy and minimize side effects. This review examines the evidence for chronotherapeutic treatment for solid tumors, including chrono-chemotherapy, chrono-radiotherapy, and alternative chronotherapeutics, and discusses areas for further research and challenges in the field.
Article
Oncology
Qiyi Yi, Youguang Pu, Fengmei Chao, Po Bian, Lei Lv
Summary: This study identifies ACAP1 as a novel lymphocyte marker that is essential for the normal function of lymphocytes. ACAP1 deficiency is associated with poor prognosis and immunotherapeutic response in multiple cancer types. It suggests that ACAP1 could be a useful indicator for predicting response to immunotherapy and guiding appropriate cancer therapy.
Article
Oncology
Laura K. Fogli, Rosemarie Aurigemma, Connie L. Sommers, Anju Singh, Kasia Bourcier, Marc S. Ernstoff
Summary: Cell-based immunotherapies have shown remarkable success in treating hematologic malignancies, but have limited efficacy in solid tumor patients. Key challenges in developing cell-based immunotherapy for solid tumors include scientific, technical, clinical, and regulatory barriers. The research community may benefit from NCI support in areas such as tumor target selection, clinical trial harmonization, manufacturing support, and standard operating procedures.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Multidisciplinary Sciences
Estelle Baulu, Celia Gardett, Nicolas Chuvin, Stephane Depil
Summary: T cell engineering has revolutionized cancer immunotherapy. Chimeric antigen receptor T cells have shown great efficacy in treating B cell malignancies, while T cells expressing engineered T cell receptors (TCR-T cells) offer a promising therapeutic alternative for solid tumors. This review summarizes clinical results and methods for identifying and optimizing TCR candidates, discusses challenges such as toxicity assessment and resistance mechanisms, and highlights future directions in the field.
Review
Immunology
Biaoru Li
Summary: Tumor-infiltrating lymphocytes (TILs) play a key role in controlling and treating tumor diseases. Cultured TILs have been shown to effectively cure patients with melanoma. Our laboratory and clinicians have published numerous papers on TILs. Over the past 30 years, we have been studying the efficacy of TILs in treating solid tumors.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Dharmindra Dulal, Andrew Boring, David Terrero, Tiffany Johnson, Amit K. Tiwari, Dayanidhi Raman
Summary: Physiologically, immune checkpoints such as CTLA-4 and PD-1 promote tolerance to self-antigens and prevent autoimmunity. In cancer, tumor cells or stromal cells from the tumor microenvironment effectively engage these immune checkpoints, leading to CD8(+) T lymphocyte inhibition and immunotherapy failure. Resistance to FDA-approved therapeutic antibodies arises from upregulated expression of alternate immune checkpoints. Targeting both traditional and alternate immune checkpoints may benefit immune-refractory tumors.
Review
Oncology
Daniele Presti, Filippo Gustavo Dall'Olio, Benjamin Besse, Joana Mourato Ribeiro, Antonio Di Meglio, Davide Soldato
Summary: This study systematically reviewed the role of tumor infiltrating lymphocytes (TILs) as predictors of response to immunotherapy in solid tumors. The results showed associations between TILs and treatment outcomes in melanoma and breast cancer. However, no definitive conclusion can be drawn on the predictive role of TILs, and further studies are needed to evaluate TILs and establish standard cut-off values for high and low TILs.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2022)
Article
Oncology
Najmeh Bozorgmehr, Isobel Okoye, Siavash Mashhouri, Julia Lu, Petya Koleva, John Walker, Shokrollah Elahi
Summary: This study revealed the immunosuppressive nature of CD71(+) erythroid cells and their association with response to PD-L1 therapy. The expansion of these cells was found to be related to anemia and poor immunotherapy outcomes. Additionally, EPO treatment was shown to promote the generation of these cells and attenuate the therapeutic effects of ICIs.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Anders Handrup Kverneland, Christopher Aled Chamberlain, Troels Holz Borch, Morten Nielsen, Sofie Kirial Mork, Julie Westerlin Kjeldsen, Cathrine Lund Lorentzen, Lise Pyndt Jorgensen, Lene Buhl Riis, Christina Westmose Yde, Ozcan Met, Marco Donia, Inge Marie Svane
Summary: This study demonstrated high success rates of TIL expansion and tumor regressions in multiple solid cancer types when combining TIL ACT with CPIs. In vitro tumor reactivity was positively associated with treatment outcomes.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
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
Oncology
Javier Martin-Broto, Nadia Hindi, Giovanni Grignani, Alessandra Merlini, Tony Ibrahim, Axel Le Cesne
Summary: Trabectedin serves as a recommended second-line option for advanced soft tissue sarcoma, offering long-term tumor control and preserved quality of life. Three case studies demonstrate the lasting responses patients can achieve with second-line trabectedin.
Article
Oncology
Giovanni Grignani, Alessandra Merlini, Sandra Aliberti
Summary: This article is a case study of a woman with uterine leiomyosarcoma, highlighting the importance of balancing efficacy and toxicity in treatment choices for this rare disease, in order to allow patients to maintain a normal life.
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
Oncology
Samuel Hidalgo-Rios, Jaime Carrillo-Garcia, David S. Moura, Silvia Stacchiotti, Antonio Lopez-Pousa, Andres Redondo, Antoine Italiano, Antonio Gutierrez, Giovanni Grignani, Nadia Hindi, Jose-Antonio Lopez-Guerrero, Xavier Garcia del Muro, Javier Martinez Trufero, Emanuela Palmerini, Ana Sebio Garcia, Daniel Bernabeu, Axel Le Cesne, Paolo Giovanni Casali, Jean-Yves Blay, Josefina Cruz Jurado, Javier Martin-Broto
Summary: The retrospective analysis of peripheral inflammatory indexes in patients with advanced solitary fibrous tumour (SFT) treated with pazopanib demonstrated that high baseline neutrophil/lymphocyte ratio (NLR) and red cell distribution width (RDW) values were independent prognostic biomarkers for worse outcomes in terms of progression-free survival (PFS) and overall survival (OS).
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
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.
Article
Oncology
Paola Zagami, Alessandro Comandone, Marco Fiore, Giacomo Giulio Baldi, Giovanni Grignani, Bruno Vincenzi, Alessandro Gronchi, Gabriele Antonarelli, Antonella Boglione, Elisabetta Pennacchioli, Giuseppe Curigliano, Fabio Conforti, Tommaso Martino De Pas
Summary: In this retrospective observational study, GI leiomyosarcomas (GI-LMS) were found to be a rare and highly aggressive subtype of sarcomas. Localized GI-LMS can be cured with appropriate surgery and adjuvant chemotherapy, while de-novo metastatic disease has a poor prognosis. Therefore, efforts are needed to understand the biology and clinical behavior of GI-LMS and develop effective treatment strategies.