Review
Medicine, Research & Experimental
Kerry A. Whalen, Kavya Rakhra, Naveen K. Mehta, Alexander Steinle, Jennifer S. Michaelson, Patrick A. Baeuerle
Summary: The field of immuno-oncology has revolutionized cancer patient care, but there are still challenges with current therapeutic approaches targeting T cells. Engaging the innate immune system, especially natural killer (NK) cells, has emerged as a promising modality in immunotherapy. This review focuses on therapeutic strategies that selectively engage NK cells for cancer therapy, particularly targeting the activating receptors NKG2D and CD16A.
Article
Oncology
Maria B. Bordignon, Ayelen I. Pesce Viglietti, Estefania P. Julia, Maria B. Sanchez, Alexander Roelle, Pablo Mando, Luciana Sabatini, Alexis Ostinelli, Manglio M. Rizzo, Maria M. Barrio, Jose Mordoh, Leonardo Fainboim, Estrella M. Levy
Summary: Adaptive NK cells, which expand after HCMV infection, have stronger cytokine production, longer life and persistence compared to conventional NK cells, making them valuable for cancer immunotherapy. In this study, adaptive NK cell subpopulations were characterized in HER2+ breast cancer patients and found to overlap to a lesser extent than in healthy donors. However, no significant phenotypic differences were observed between patients and donors. Additionally, the presence of both Fc epsilon RI gamma- and NKG2C+ was necessary for increased IFN-gamma production in patients, while the presence of NKG2C alone was sufficient in donors. These findings suggest that adaptive NK cell subsets may play a role in therapeutic approaches targeting tumor antigens.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Christian Kellner, Sebastian Lutz, Hans-Heinrich Oberg, Daniela Wesch, Anna Otte, Katarina J. Diemer, Hauke Wilcken, Dirk Bauerschlag, Claus-Christian Glueer, Christian Wichmann, Dieter Kabelitz, Jeanette H. W. Leusen, Katja Klausz, Andreas Humpe, Martin Gramatzki, Matthias Peipp
Summary: Combining NKG2D ligand ULBP2 with HER2-targeting scFv can effectively trigger NK cell killing of HER2-positive breast cancer cells. This immunoligand not only induces tumor cell lysis, but also enhances antibody-dependent cell-mediated cytotoxicity against tumor cells.
BIOLOGICAL CHEMISTRY
(2022)
Review
Cell Biology
Jagoda Siemaszko, Aleksandra Marzec-Przyszlak, Katarzyna Bogunia-Kubik
Summary: Natural Killer (NK) cells are natural cytotoxic cells of the innate immune system that can recognize and attack transformed or infected cells through their NKG2D receptor, which has significant immunological functions and clinical relevance.
Review
Immunology
Massimo Fantini, Philip Martin Arlen, Kwong Yok Tsang
Summary: Natural killer (NK) cells are important components of the innate immune system that can recognize and suppress the proliferation of cancer cells. Strategies such as boosting NK cells with modulatory cytokines, adoptive NK cell therapy, and the combination of engineered NK cells with monoclonal antibodies (mAbs) that mediate antibody-dependent cell-mediated cytotoxicity (ADCC) have been developed to enhance the antitumor activity of NK cells. The combination of engineered NK cells with mAbs with higher affinity for CD16 expressed on NK cells shows promise in providing more effective and higher-quality treatments for cancer patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cell & Tissue Engineering
Hans Klingemann
Summary: The NK-92 cell line is a highly active blood natural killer (NK) cell that exhibits broader and greater cytotoxicity. It has significant implications in both research and clinical treatment, showing great potential in the treatment of cancer and infections.
Article
Oncology
Pablo Mando, Sergio G. Rivero, Manglio M. Rizzo, Marina Pinkasz, Estrella M. Levy
Summary: This article summarizes the progress and strategies of immune response in antibody treatment for HER2-amplified breast cancer. Dual HER2 blockade is the standard of care in both early and advanced disease. In cases of disease relapse or progression, antibody-dependent cell-mediated cytotoxicity may be affected by various factors.
Review
Oncology
Nicky A. Beelen, Femke A. Ehlers, Gerard M. J. Bos, Lotte Wieten
Summary: This review provides an overview of the impact of inhibitory KIR and NKG2A on NK cell-mediated ADCC response, emphasizing the rationale for combination strategies targeting inhibitory immune checkpoints and ADCC triggering antibodies.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Haeryung Cho, Woo-Chang Son, Young-Shin Lee, Eun Jung Youn, Chi-Dug Kang, You-Soo Park, Jaeho Bae
Summary: Histone acetylation is an epigenetic mechanism that regulates gene expression, including NKG2D ligands. Specific types of HDAC genes, particularly HDAC1 and HDAC2, may be key regulators of NKG2D ligand expression. Inhibiting HDAC1 and HDAC2 could induce NKG2D ligand expression, potentially enhancing NK cell-mediated anti-cancer immunity.
Review
Immunology
Feifei Li, Sheng Liu
Summary: This review provides an overview of the role of natural killer (NK) cells and antibody-dependent cellular cytotoxicity (ADCC) in targeted therapy of HER2-positive breast cancer, as well as recent strategies to leverage our knowledge of NK cells and ADCC as an immunotherapy approach.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Lois Coenon, Martin Villalba
Summary: This review provides an overview of the latest strategies employed to improve antibody-dependent NK cell cytotoxicity, by enhancing the biological function of CD16a receptor.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chunmei Yang, Cheng Qian, Tingting Zhang, Weiwei Zheng, Shan Zhang, Shijun Wang, Aiyun Wang, Yang Zhao, Yin Lu
Summary: Tanshinol can reverse the inhibitory effect of TGF-beta 1 on NK cell functions, promoting NK cells to carry out immune attacks on tumor cells.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2021)
Article
Biochemistry & Molecular Biology
Polina Kaidun, Samuel J. Holzmayer, Sarah M. Greiner, Anna Seller, Christian M. Tegeler, Ilona Hagelstein, Jonas Mauermann, Tobias Engler, Andre Koch, Andreas D. Hartkopf, Helmut R. Salih, Melanie Maerklin
Summary: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options. The development of bispecific fusion proteins (BFPs) targeting NKG2DLs has shown promising results in activating NK and T cells against TNBC cells, leading to efficient eradication of tumors. This approach could be a valuable addition to the current treatment options for TNBC patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Nicky A. Beelen, Merel R. Aberle, Virginia Bruno, Steven W. M. Olde Damink, Gerard M. J. Bos, Sander S. Rensen, Lotte Wieten
Summary: This study evaluated the cytotoxic potential of adoptive NK cells against pancreatic cancer organoids and found that ADCC-inducing antibodies can enhance NK cell anti-tumor responses.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Vanna Imsirovic, Maja Lenartic, Felix M. M. Wensveen, Bojan Polic, Vedrana Jelencic
Summary: Natural killer (NK) cells, important in early defense against tumors and virally infected cells, are regulated by a balance of activating and inhibitory receptors. However, some activating receptors lack an inhibitory partner. This study shows that activating NK cell receptors without inhibitory partners are not a "master" signal, but instead their activity is controlled through regulation of other activating receptors. This finding has potential implications for the development of NK cell-based cancer immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Tiziana Triulzi, Giampaolo Bianchini, Serena Di Cosimo, Tadeusz Pienkowski, Young-Hyuck Im, Giulia Valeria Bianchi, Barbara Galbardi, Matteo Dugo, Loris De Cecco, Ling-Ming Tseng, Mei-Ching Liu, Begona Bermejo, Vladimir Semiglazov, Giulia Viale, Juan de la Haba-Rodriguez, Do-Youn Oh, Brigitte Poirier, Pinuccia Valagussa, Luca Gianni, Elda Tagliabue
Summary: In HER2-positive/ER-positive breast cancer, the 41-gene classifier TRAR has been identified as an independent predictor of pCR, serving as a promising tool to select patients responsive to anti-HER2-based neoadjuvant therapy and to assist in treatment escalation and de-escalation strategies.
MOLECULAR ONCOLOGY
(2022)
Article
Oncology
Sara Pizzamiglio, Giulia Cosentino, Chiara M. Ciniselli, Loris De Cecco, Alessandra Cataldo, Ilaria Plantamura, Tiziana Triulzi, Sarra El-abed, Yingbo Wang, Mohammed Bajji, Paolo Nuciforo, Jens Huober, Susan L. Ellard, David L. Rimm, Andrea Gombos, Maria Grazia Daidone, Paolo Verderio, Elda Tagliabue, Serena Di Cosimo, Marilena V. Iorio
Summary: The study evaluated the predictive and prognostic value of basal primary tumor miRNA expression profile in trastuzumab treatment and identified miRNA signatures associated with clinical outcomes. These miRNA markers have the potential to be a useful tool in identifying patients with differential responses to trastuzumab-based neoadjuvant therapy.
Article
Oncology
Francesca Ligorio, Serena Di Cosimo, Paolo Verderio, Chiara Maura Ciniselli, Sara Pizzamiglio, Lorenzo Castagnoli, Matteo Dugo, Barbara Galbardi, Roberto Salgado, Sherene Loi, Stefan Michiels, Tiziana Triulzi, Elda Tagliabue, Sarra El-Abed, Miguel Izquierdo, Evandro de Azambuja, Paolo Nuciforo, Jens Huober, Luca Moscetti, Wolfgang Janni, Maria Antonia Coccia-Portugal, Paola Antonia Corsetto, Antonino Belfiore, Daniele Lorenzini, Maria Grazia Daidone, Andrea Vingiani, Luca Gianni, Serenella Maria Pupa, Giampaolo Bianchini, Giancarlo Pruneri, Claudio Vernieri
Summary: This study found that high expression of CD36 is associated with worse clinical outcomes in early-stage HER2+ BC patients treated with anti-HER2 therapy.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2022)
Review
Oncology
Martina Di Modica, Valeria Arlotta, Lucia Sfondrini, Elda Tagliabue, Tiziana Triulzi
Summary: Microbiota plays a key role in cancer by influencing various host physiological functions and affecting the efficacy of anticancer treatments. The involvement of the breast microbiota in breast cancer has been extensively studied. This review focuses on the impact of gut and breast microbiota on HER2+ breast cancer subtype and discusses the potential of defining microbial signatures associated with disease aggressiveness, treatment response, and therapy toxicity. The mechanisms of microorganism-host interactions and the possibility of microbiota editing in breast cancer prevention and treatment optimization are also explored.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Milena Perrone, Claudia Chiodoni, Mara Lecchi, Laura Botti, Barbara Bassani, Annamaria Piva, Elena Jachetti, Matteo Milani, Daniele Lecis, Elda Tagliabue, Paolo Verderio, Sabina Sangaletti, Mario P. Colombo
Summary: Cancer can reprogram the bone marrow niche through the BM mesenchymal stem cells (MSC) and IL-1B/ATF3 signaling pathway, which promotes myeloid cell differentiation and tumor development. The expression of CD11b thorn population in the peripheral blood can be used as a potential biomarker for early diagnosis of breast cancer. This study suggests that targeting IL-1B or ATF3 may have therapeutic benefits for breast cancer patients.
Article
Biochemistry & Molecular Biology
Valentino Le Noci, Giancarla Bernardo, Giacomo Manenti, Gabriele Infante, Dariush Khaleghi Hashemian, Lucia Minoli, Simone Canesi, Francesca Bianchi, Tiziana Triulzi, Stefania Arioli, Loris De Cecco, Simone Guglielmetti, Federico Ambrogi, Camilla Recordati, Nicoletta Gagliano, Elda Tagliabue, Michele Sommariva, Lucia Sfondrini
Summary: This study explores the impact of perturbing lung microbiota on lung cancer development by using antibiotics or probiotic aerosol. The results suggest that L.RGG aerosol can reduce tumor nodules and Tregs in the lung, while increasing the expression of immunoglobulin joining chain and promoting B and CD4 T cell infiltration. This non-invasive strategy shows efficacy in impairing lung cancer growth by promoting local immunity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Francesca Bianchi, Annalisa Cappella, Nicoletta Gagliano, Lucia Sfondrini, Alessandra Stacchiotti
Summary: A healthy gut is essential for maintaining a balanced intestinal microbiota, which plays a crucial role in human metabolism. Dysbiosis, an imbalance in gut microbiota, is associated with cardiovascular diseases. Polyphenols have beneficial effects on the gut microbiota and may have the potential to prevent and treat cardiovascular diseases.
Article
Oncology
Giancarla Bernardo, Valentino Le Noci, Emerenziana Ottaviano, Loris De Cecco, Chiara Camisaschi, Simone Guglielmetti, Martina Di Modica, Giorgio Gargari, Francesca Bianchi, Serena Indino, Patrizia Sartori, Elisa Borghi, Michele Sommariva, Elda Tagliabue, Tiziana Triulzi, Lucia Sfondrini
Summary: This study highlights the significant influence of mammary tumor microbiota on local immune status and the relevance of its treatment with antibiotics, in combination with breast cancer therapies.
Article
Oncology
Arsela Prelaj, Monica Ganzinelli, Francesco Trovo, LailaC. Roisman, Alessandra Laura Giulia Pedrocchi, Sokol Kosta, Marcello Restelli, Emilia Ambrosini, Massimo Broggini, Gabriella Pravettoni, Dario Monzani, Alessandro Nuara, Ramon Amat, Nikos Spathas, Michael Willis, Alexander Pearson, James Dolezal, Laura Mazzeo, Sabina Sangaletti, Ana Maria Correa, Alfonso Aguaron, Iris Watermann, Crina Popa, Giulia Raimondi, Tiziana Triulzi, Stefan Steurer, Giuseppe Lo Russo, Helena Linardou, Nir Peled, Enriqueta Felip, Martin Reck, Marina Chiara Garassino
Summary: Despite the success of immunotherapy in treating aNSCLC, only a fraction of patients truly benefit from it. PD-L1, the only biomarker used for predicting IO outcomes, is not sufficient due to the complex nature of the immune system and tumor microenvironment. Artificial Intelligence and Machine Learning are now utilized to develop decision-making tools to match treatments with individual patients, improve outcomes, and reduce the economic burden. I3LUNG, a funded study, aims to promote individualized treatment in aNSCLC through AI-based tools and create an integrated platform for IO administration.
CLINICAL LUNG CANCER
(2023)
Review
Biochemistry & Molecular Biology
Stefania Mantovani, Barbara Oliviero, Stefania Varchetta, Alessandra Renieri, Mario U. Mondelli
Summary: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a devastating pandemic since March 2020. Toll-like receptors (TLRs) have been shown to be involved in the dysregulated immune response observed in patients with severe COVID-19. TLR2, TLR3, TLR4, and TLR7 have been associated with COVID-19 severity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Giancarla Bernardo, Valentino Le Noci, Martina Di Modica, Elena Montanari, Tiziana Triulzi, Serenella M. Pupa, Elda Tagliabue, Michele Sommariva, Lucia Sfondrini
Summary: Emerging evidence suggests that the composition of the gut microbiota is closely associated with breast cancer progression. In addition to their role in modulating the immune response and estrogen levels, recent research has revealed the presence of microbes in the breast tissue, which was once considered sterile, and their potential contribution to tumor progression. Specific bacterial species enriched in breast tumors have been identified, and their mechanisms of influencing cancer progression have been elucidated. Understanding the crosstalk between the gut/mammary microbiota and breast cancer holds promise for developing innovative therapeutic approaches.