Article
Oncology
Katherine Walwyn-Brown, Jason Pugh, Alexander T. H. Cocker, Niassan Beyzaie, Bernhard B. Singer, Daniel Olive, Lisbeth A. Guethlein, Peter Parham, Zakia Djaoud
Summary: Gamma delta T cells stimulated by phosphoantigens (pAg) have anti-tumor effects and suppress NK cell responses, but have no effect on antigen-specific CD8(+) T cell responses. This immunosuppression of NK cells by gamma delta T cells has a significant impact and provides a new perspective for optimizing the use of gamma delta T cells in cancer immunotherapy.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Fernanda Scopelliti, Valentina Dimartino, Caterina Cattani, Andrea Cavani
Summary: This study found that TRPA1 channels are highly expressed in the CD56(dim)CD16(+) subpopulation of NK cells, and their activation can increase cell-mediated cytotoxicity against tumors while also regulating the survival of NK cells to limit excessive cytotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Olivier Demaria, Laurent Gauthier, Marie Vetizou, Audrey Blanchard Alvarez, Constance Vagne, Guillaume Habif, Luciana Batista, William Baron, Nourhene Belaid, Mathilde Girard-Madoux, Cedric Cesari, Melody Caratini, Frederic Bosco, Olivier Benac, Julie Lopez, Aurore Fenis, Justine Galluso, Sylvia Trichard, Barbara Carrette, Florent Carrette, Aurelie Maguer, Solene Jaubert, Audrey Sansaloni, Robin Letay-Drouet, Camille Kosthowa, Naouel Lovera, Arnaud Dujardin, Fabien Chanuc, Melanie Le Van, Sivan Bokobza, Nicolas Jarmuzynski, Camille Fos, Nicolas Gourdin, Romain Remark, Eric Lechevallier, Nicolas Fakhry, Sebastien Salas, Jean-Laurent Deville, Roger Le Grand, Cecile Bonnafous, Lukas Vollmy, Agnes Represa, Sabrina Carpentier, Benjamin Rossi, Ariane Morel, Stephanie Cornen, Ivan Perrot, Yannis Morel, Eric Vivier
Summary: This study presents the design of tetraspecific molecules that can activate natural killer cells for cancer therapy. The tetraspecific molecules selectively activate and proliferate natural killer cells, and the binding to tumor-associated antigens triggers cell cytotoxicity and cytokine production. In animal experiments, the tetraspecific molecules control tumor growth and accumulate at the tumor site. Furthermore, they can deplete circulating B cells without causing toxicity in non-human primates.
CELL REPORTS MEDICINE
(2022)
Article
Oncology
Grace Lee, Sheela Karunanithi, Bruce Posner, Hanspeter Niederstrasser, Hong Cheng, Yuriy Federov, Shivaprasad Manjappa, Karam Musaitif, Huaiyu Wang, Zachary Jackson, David Wald
Summary: Our work led to the identification of a promising compound that potently increases NK cell-mediated killing of a variety of different cancer cells, but has no impact on the killing of normal cells. This compound demonstrates the utility of this screening assay.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Immunology
Christian Binder, Felix Sellberg, Filip Cvetkovski, Stefan Berg, Erik Berglund, David Berglund
Summary: The study showed that siplizumab increased NK cell activation by binding to Fc gamma RIIIA, suggesting potential application in inhibiting NK cell activation. However, the inhibitory effects of CD2 blockade on natural cytotoxicity and antibody-dependent cytotoxicity remain unclear.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lingtong Zhi, Meichen Yin, Xin Su, Zikang Zhang, Hui Lu, Mingfeng Li, Changjiang Guo, Zhiyuan Niu, Xuan Zhang, Wuling Zhu
Summary: Engineered natural killer (NK) cell-based therapies have shown broad potential in cancer treatment. The inhibitory pathway, however, remains a major obstacle. Researchers have designed a chimeric switch-receptor (CSR) PD1-DAP10-41BB to convert the inhibitory signal into a positive one. The CSR-expressing NK92 cells demonstrated enhanced cytotoxicity and suppressed tumor growth in mouse models. This study highlights the potential of engineered NK cells to treat a wide range of solid tumors.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Immunology
Bert Malengier-Devlies, Jessica Filtjens, Kourosh Ahmadzadeh, Bram Boeckx, Jessica Vandenhaute, Amber De Visscher, Eline Bernaerts, Tania Mitera, Cato Jacobs, Lore Vanderbeke, Pierre Van Mol, Yannick Van Herck, Greet Hermans, Philippe Meersseman, Alexander Wilmer, Mieke D. Gouwy, Abhishek Garg, Stephanie Humblet-Baron, Frederik De Smet, Kimberly Martinod, Els Wauters, Paul Proost, Carine Wouters, Georges Leclercq, Diether Lambrechts, Joost Wauters, Patrick Matthys
Summary: NK cells in COVID-19 patients display an activated phenotype and show significant differences between different stages of infection. Early-stage patients have increased expression of cytotoxic molecules, while late-stage patients show enhanced levels of cytokines. The activation of NK cells is correlated to neutrophil count and IL-15 levels, but cytotoxic killing is normal.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Sizhen Wang, Xiaohui Zhang, Xuemei Zou, Maorong Wen, Chi Gan, Xiaochun Jiang, Min Li, Rongxi Shen, Daojun Zhu, Anlong Yao, Yu Fang, Bernard A. Fox, Hong-Ming Hu, Guangjie Yu, Xinbo Wang
Summary: Adoptive cell therapy (ACT) using expanded tumor-infiltrating lymphocytes (TIL) or TCR gene-modified T cells (TCR-T) can induce tumor regression in patients with advanced pancreatic ductal adenocarcinoma (PDAC). However, the scarcity of TILs that recognize mutant KRAS and the poor immunogenicity of PDAC limit the widespread application of mutant KRAS-centric ACT. Researchers have attempted to increase the production of TILs by using K562-based artificial antigen-presenting cells (aAPC), but this leads to a loss of specificity to mutant KRAS. By using tandem mini gene-modified autologous T cells (TMG-T) as a novel aAPC, the generation of TIL cultures specifically reactive to mutant KRAS has been successfully achieved.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Immunology
Guijie Kang, Xueqin Zhao, Jiafeng Sun, Chen Cheng, Cen Wang, Longxiang Tao, Lu Zong, Wenwei Yin, Jingjing Cong, Jing Li, Xuefu Wang
Summary: The characteristics of CD39+ NK cells in humans were investigated and it was found that the proportion of CD39+ NK cells was relatively low in healthy individuals. However, CD39+ NK cells expressed higher levels of CD107a. Stimulation with K562 cells or IL-12/IL-18 activated CD39+ NK cells to express higher levels of CD107a, IFN-gamma, and TNF-alpha. IL-15 induced the generation of CD39+ NK cells, while A2AR ligation suppressed their generation by inhibiting IL-15 signaling.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Shushu Zhao, Shuting Wu, Sheng Jiang, Xiaoyu Zhou, Gan Zhao, Bin Wang
Summary: Most cancer immunotherapy approaches focus on stimulating CD8(+) T cells to reject tumor cells. However, the suppressive micro-environment created by regulatory T cells (Tregs) has limited the success of preclinical approaches in clinical settings. A recent study showed that transient interruption of Tregs induced CD8(+) T cell responses against tumors in an animal model. The study also demonstrated that transient Treg depletion during primary tumor challenge can result in long-lasting protection and activation of skin-resident memory T cells (sT(RM)) for rejecting rechallenged tumors.
SCIENTIFIC REPORTS
(2023)
Review
Cell Biology
Chenxin Wang, Jingjing Liu, Wei Li
Summary: In recent years, immune cell-based therapies using primary T cells and NK cells armed with chimeric antigen receptors have shown great success in treating refractory malignancies. However, the autologous origin of these cells limits their accessibility to patients due to high cost, product quality variations, and treatment delays. Therefore, the development of universal immune cell products from pluripotent stem cells (PSCs) is necessary to overcome these challenges and provide a large supply of engineered immune cells. This review discusses the advances in PSC-derived immune cell differentiation approaches and their potential in treating various diseases.
CELL PROLIFERATION
(2023)
Review
Oncology
Beatriz Cozar, Marco Greppi, Sabrina Carpentier, Emilie Narni-Mancinelli, Laura Chiossone, Eric Vivier
Summary: NK cells play a crucial role in immune responses to tumors by killing target cells and producing cytokines, but they can become dysfunctional in the immunosuppressive tumor microenvironment. This article provides an overview of NK tumor infiltration and surveillance, as well as the mechanisms by which NK cells become dysfunctional.
Article
Biochemistry & Molecular Biology
Chantal Reina-Ortiz, M. Pilar Mozas, David Ovelleiro, Fei Gao, Martin Villalba, Alberto Anel
Summary: Therapies based on allogenic Natural Killer (NK) cells, specifically expanded and activated NK (eNK) cells, have shown significant cytotoxicity against hematological cancers. This study aims to understand the changes that occur in healthy NK cells during the expansion process in order to develop a more potent eNK-based therapy. MicroRNA (miRNA) expression analysis revealed changes in the expression of 64 miRNAs, highlighting the up-regulation of miRs-146a, -124, -34a, and -10a, which play a key role in cell survival, and the down-regulation of miRs-199a, -223, and -340, associated with increased NK cell cytotoxicity. Validation experiments confirmed the functional importance of these miRNAs and demonstrated the wide variety of changes in eNK cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Takuma Asahi, Shinya Abe, Guangwei Cui, Akihiro Shimba, Tsukasa Nabekura, Hitoshi Miyachi, Satsuki Kitano, Keizo Ohira, Johannes M. Dijkstra, Masaki Miyazaki, Akira Shibuya, Hiroshi Ohno, Koichi Ikuta
Summary: Group 1 innate lymphoid cells (G1-ILCs) are crucial for immune responses against infection and cancer. This study reveals the development of a cytotoxic ILC1 subset in the liver and demonstrates its killing activity and unique ontogeny.
Article
Geriatrics & Gerontology
Rongjiao Liu, Qizhi Luo, Weiguang Luo, Ling Wan, Quan Zhu, Xiangli Yin, Xiaofang Lu, Zixuan Song, Leiyan Wei, Zhiqing Xiang, Yizhou Zou
Summary: In this study, a soluble NKCAR was designed to trigger NK cell cytotoxicity by binding with the ligand MICA through the NKG2D receptor expressed on NK cells. The NKCAR showed bifunctional activity, recognizing both the CD20 antigen of target cells and the NKG2D receptor of NKL cells. The soluble NKCAR mediated the killing of CD20(+) Daudi cells in vitro, indicating its potential clinical application for killing target tumor cells.
Article
Oncology
Clement Dabiri, Judicael Hotton, Karl Wehbe, Hugo Gornes, Christian Garbar, Francois Guillemin, Vivien Ceccato
Summary: The Grisotti technique is an easily reproducible procedure without major complications, allowing for satisfactory central lumpectomy, correction of central glandular defect, and reconstruction of a new areola. Postoperative satisfaction rates for both patients and surgeons are high, especially in the appearance of the breasts after radiotherapy.
Article
Hematology
Gabrielle Sonigo, Alizee Bozonnat, Maelle Dumont, Nicolas Thonnart, Caroline Ram-Wolff, Adele de Masson, Martine Bagot, Armand Bensussan, Anne Marie-Cardine
Article
Multidisciplinary Sciences
Beatrice Romier, Cedric Dray, Laetitia Vanalderwiert, Amandine Wahart, Thinhinane Hocine, Alizee Dortignac, Christian Garbar, Corinne Garbar, Camille Boulagnon, Nicole Bouland, Pascal Maurice, Amar Bennasroune, Herve Sartelet, Laurent Martiny, Laurent Duca, Philippe Valet, Sebastien Blaise
Summary: Recent studies have shown that apelin deficiency in mice leads to vascular stiffening and wall remodeling. The absence of apelin expression results in inflammation of adipose tissue and ECM remodeling, affecting vascular homeostasis.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Marie-Lea Gauci, Jerome Giustiniani, Clemence Lepelletier, Christian Garbar, Nicolas Thonnart, Nicolas Dumaz, Arnaud Foussat, Celeste Lebbe, Armand Bensussan, Anne Marie-Cardine
Summary: Research has found that CD160 is highly expressed in the tumor tissues of melanoma patients. Melanoma cells express CD160-GPI isoform and release soluble form (sCD160), which inhibits the cytotoxic activity of NK cells. In addition, sCD160 is found in the serum of melanoma patients and is associated with increased tumor dissemination.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Oncology
Leonard Laurent, Mathias Brugel, Claire Carlier, Florentin Clere, Aurelie Bertrand, Damien Botsen, Camille Boulagnon-Rombi, Veronique Dalstein, Adeline Debreuve-Theresette, Sophie Deguelte, Christian Garbar, Rachid Mahmoudi, Antonin Marechal, David Morland, Jean-Baptiste Rey, Claire Schvartz, Catherine Vallet, Yacine Merrouche, Florian Slimano, Olivier Bouche
Summary: The COVID-19 pandemic had a significant impact on the cancer care pathway, particularly in screening and diagnosis. The second wave of the outbreak had an evident effect on medical announcement procedures, radiotherapy sessions, and multidisciplinary tumor board meetings. Despite some recovery between lockdowns, the activity level remained stagnant and a backlog persisted.
Article
Oncology
Louise Rethacker, Maxime Boy, Valeria Bisio, France Roussin, Jordan Denizeau, Anne Vincent-Salomon, Edith Borcoman, Christine Sedlik, Eliane Piaggio, Antoine Toubert, Nicolas Dulphy, Anne Caignard
Summary: Innate lymphoid cells (ILCs), including NK cells and ILC3, play important roles in tissue immune homeostasis and tumor surveillance. In human lymph nodes, NK cells and ILC3s are the prominent subpopulations. However, in tumor-draining lymph nodes and breast cancer tumors, NK cells are more abundant while proportions of ILC3 subsets are low. The local tumor microenvironment inhibits NK cell functions through downregulation of a specific receptor, but cytokine stimulation can restore their functionality.
Article
Oncology
Lucie Coillard, Frederic Guaddachi, Maelle Ralu, Eva Brabencova, Christian Garbar, Armand Bensussan, Morgane Le Bras, Jacqueline Lehmann-Che, Sebastien Jauliac
Summary: Further research is needed to understand the biology and metastasis formation of luminal breast cancers. The detection of the NFAT3/RERG complex may serve as a non-invasive marker for axillary lymph node colonization.
FRONTIERS IN ONCOLOGY
(2022)
Correction
Oncology
Lucie Coillard, Frederic Guaddachi, Maelle Ralu, Eva Brabencova, Christian Garbar, Armand Bensussan, Morgane Le Bras, Jacqueline Lehmann-Che, Sebastien Jauliac
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Maxime Boy, Valeria Bisio, Lin-Pierre Zhao, Fabien Guidez, Berenice Schell, Emilie Lereclus, Guylaine Henry, Juliette Villemonteix, Fernando Rodrigues-Lima, Katia Gagne, Christelle Retiere, Lise Larcher, Rathana Kim, Emmanuelle Clappier, Marie Sebert, Arsene Mekinian, Olivier Fain, Anne Caignard, Marion Espeli, Karl Balabanian, Antoine Toubert, Pierre Fenaux, Lionel Ades, Nicolas Dulphy
Summary: NK cells in MDS patients with TET2 mutations exhibit phenotypic defects, including increased DNA methylation, reduced expression of KIR, perforin, and TNF-a. Inhibition of TET2 in NK cells from healthy donors decreases their cytotoxicity, indicating its critical role in NK cell function. Treatment with azacytidine enhances KIR and cytolytic protein expression, as well as IFN-gamma production in NK cells from patients.
NATURE COMMUNICATIONS
(2023)
Letter
Dermatology
Andreea Calugareanu, Adele de Masson, Maxime Battistella, Laurence Michel, Caroline Ramwolff, Jean-David Bouaziz, Sandy Peltier, Armand Bensussan, Martin Bagot, Gabor Dobos
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Oncology
Lin-Pierre Zhao, Marie Sebert, Arsene Mekinian, Olivier Fain, Marion Espeli, Karl Balabanian, Nicolas Dulphy, Lionel Ades, Pierre Fenaux
Article
Multidisciplinary Sciences
Adrienne Anginot, Julie Nguyen, Zeina Abou Nader, Vincent Rondeau, Amelie Bonaud, Maria Kalogeraki, Antoine Boutin, Julia P. Lemos, Valeria Bisio, Joyce Koenen, Lea Hanna Doumit Sakr, Amandine Picart, Amelie Coudert, Sylvain Provot, Nicolas Dulphy, Michel Aurrand-Lions, Stephane J. C. Mancini, Gwendal Lazennec, David H. McDermott, Fabien Guidez, Claudine Blin-Wakkach, Philip M. Murphy, Martine Cohen-Solal, Marion Espeli, Matthieu Rouleau, Karl Balabanian
Summary: WHIM Syndrome is a rare immunodeficiency caused by mutations in CXCR4 gene. This study found that 25% of WHIM patients have decreased bone mineral density and bone defects leading to osteoporosis. The researchers also discovered that impaired CXCR4 signaling disrupts cell cycle progression and osteogenic commitment of skeletal stromal/stem cells, resulting in imbalanced bone tissue.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Antonio Arulanandam, Liang Lin, Hao-Ming Chang, Martine Cerutti, Sylvie Choblet, Peng Gao, Armin Rath, Armand Bensussan, Jean Kadouche, Daniel Teper, Ofer Mandelboim, Wei Li
Summary: GPC3 is highly expressed in multiple solid tumors and is barely expressed in adult normal tissues except the placenta. NKp46 activation receptor is expressed in all-natural killer cells, including tumor-infiltrating NK cells. CYT-303 is a multifunctional antibody that targets both GPC3 and NKp46 to mediate NK cell-redirected killing of HCC tumors.
Article
Medicine, Research & Experimental
Vincent Jachiet, Laure Ricard, Pierre Hirsch, Florent Malard, Laurent Pascal, Odile Beyne-Rauzy, Pierre Peterlin, Alexandre Thibault Jacques Maria, Norbert Vey, Maud D'Aveni, Marie-Pierre Gourin, Sophie Dimicoli-Salazar, Anne Banos, Stefan Wickenhauser, Louis Terriou, Benoit De Renzis, Eric Durot, Shanti Natarajan-Ame, Anne Vekhoff, Laurent Voillat, Sophie Park, Julien Vinit, Celine Dieval, Azeddine Dellal, Vincent Grobost, Lise Willems, Julien Rossignol, Eric Solary, Olivier Kosmider, Nicolas Dulphy, Lin Pierre Zhao, Lionel Ades, Pierre Fenaux, Olivier Fain, Mohamad Mohty, Beatrice Gaugler, Arsene Mekinian
Summary: Background systemic inflammatory and autoimmune diseases (SIADs) occur in a significant proportion of myelodysplastic syndrome (MDS) patients. The recently identified VEXAS syndrome, associated with somatic mutations in UBA1, is characterized by severe inflammatory conditions and hematological abnormalities, including MDS. However, the mechanisms underlying the association between MDS and SIADs are largely unknown. This study aimed to evaluate myeloid immune cell subsets in MDS patients with and without SIAD and compare them to healthy controls.
CLINICAL AND EXPERIMENTAL MEDICINE
(2023)
Review
Surgery
Charles Marchand Crety, Sara Bellefqih, Koceila Amroun, Christian Garbar, Felix Felici
Summary: Synovial sarcoma is a rare mesenchymal tumor that commonly occurs near joints of the extremity, with gastric synovial sarcoma being extremely rare. Surgical resection is the best therapeutic approach for these tumors, with the need for immunohistochemical detection to make a conclusive diagnosis.
INTERNATIONAL JOURNAL OF SURGERY CASE REPORTS
(2021)
