RECQL4 affects MHC class II‐mediated signalling and favours an immune‐evasive signature that limits response to immune checkpoint inhibitor therapy in patients with malignant melan... by Sara Egea‐Rodriguez, Renáta Váraljai, Thierry M. Nordmann, Restuan Lubis, Manuel Philip, Florian Rambow, Alexander Roesch, Michael Flaig, Susanne Horn, Raphael Stoll, Fang Zhao, Annette Paschen, Bert Klebl, Ian D. Hickson, Dirk Schadendorf, Matthias Mann, Iris Helfrich

“…Abstract Background Cancer immunotherapy has transformed metastatic cancer treatment, yet challenges persist regarding therapeutic efficacy. …”
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First-in-human dose escalation trial to evaluate the clinical safety and efficacy of an anti-MAGEA1 autologous TCR-transgenic T cell therapy in relapsed and refractory solid tumors by Ignacio I Wistuba, Mamta Kalra, Linus Backert, Martin Wermke, Edwin R Parra, Jason John Luke, Apostolia M Tsimberidou, Sebastian Bunk, Mohammad B Hossain, Andrea Mayer-Mokler, Arun Satelli, Norbert Hilf, Steffen Walter, Cedrik M Britten, Van K Morris, Tobias A W Holderried, Winfried H Alsdorf, Katrin Wetzko, Borje S Andersson, Sandra Grund-Gröschke, Katrin Aslan, Anantha Marisetty, Swapna Satam, Jens Hukelmann, M Alper Kursunel, Karine Pozo, Andreas Acs, Melissa Baumeister, Claudia Wagner, Oliver Schoor, Ali S Mohamed, Delfi Krishna

“…Rationale of the trial Although the use of engineered T cells in cancer immunotherapy has greatly advanced the treatment of hematological malignancies, reaching meaningful clinical responses in the treatment of solid tumors is still challenging. …”
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Racial Differences in Systemic Immune Parameters in Individuals With Lung Cancer by Mitchell S. von Itzstein, MD, Jialiang Liu, PhD, Hong Mu-Mosley, PhD, Farjana Fattah, PhD, Jason Y. Park, MD, PhD, Jeffrey A. SoRelle, MD, J. David Farrar, PhD, Mary E. Gwin, MD, David Hsiehchen, MD, Yvonne Gloria-McCutchen, Edward K. Wakeland, PhD, Suzanne Cole, MD, Sheena Bhalla, MD, Radhika Kainthla, MD, Igor Puzanov, MD, MSCI, Benjamin Switzer, DO, MHSA, MS, Gregory A. Daniels, MD, PhD, Yousef Zakharia, MD, Montaser Shaheen, MD, Jianjun Zhang, MD, PhD, Yang Xie, PhD, David E. Gerber, MD

“…Methods: Patients scheduled to receive cancer immunotherapy were enrolled in a multi-institutional prospective biospecimen collection registry. …”
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Tacedinaline (CI-994), a class I HDAC inhibitor, targets intrinsic tumor growth and leptomeningeal dissemination in MYC-driven medulloblastoma while making them susceptible to anti... by Arndt Borkhardt, Nan Qin, Stephen T Keir, Darell D Bigner, Allison Cole, Matthias Wölfl, Viktoria Marquardt, Johanna Theruvath, David Pauck, Daniel Picard, Lena Blümel, Mara Maue, Jasmin Bartl, Ulvi Ahmadov, Maike Langini, Frauke-Dorothee Meyer, Joselyn Cruz-Cruz, Claus M Graef, Till Milde, Olaf Witt, Anat Erdreich-Epstein, Gabriel Leprivier, Ulf Kahlert, Anja Stefanski, Kai Stühler, Julia Hauer, Thomas Beez, Christiane B Knobbe-Thomsen, Ute Fischer, Jörg Felsberg, Finn K Hansen, Rajeev Vibhakar, Sujatha Venkatraman, Samuel H Cheshier, Guido Reifenberger, Thomas Kurz, Marc Remke, Siddhartha Mitra

“…Finally, combining CI-994 treatment with an anti-CD47 mAb targeting the CD47-SIRPα phagocytosis checkpoint enhanced in vitro phagocytosis and survival in tumor-bearing mice.Conclusion Together, these findings suggest a dynamic relationship between MYC amplification and innate immune suppression in MYC amplified MB and support further investigation of phagocytosis modulation as a strategy to enhance cancer immunotherapy responses.…”
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The Metabolic Features of Tumor-Associated Macrophages: Opportunities for Immunotherapy? by Sonja S. Mojsilovic, Slavko Mojsilovic, Victor H. Villar, Juan F. Santibanez

“…Also, new macrophage-based cell therapeutic technologies recently developed using chimeric antigen receptor bioengineering are exposed, which may overcome all solid tumor physical barriers impeding the current adoptive cell therapies and contribute to developing novel cancer immunotherapies.…”
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MicroRNAs as Immunotherapy Targets for Treating Gastroenterological Cancers by Yixin Yang, Christopher Alderman, Ayoub Sehlaoui, Yuan Xiao, Wei Wang

“…Since the current targeted therapies provide limited benefit to the overall response and survival, there is an urgent need for developing novel therapeutic strategy to improve the outcome of gastroenterological cancers. Immunotherapy has been developed and underwent clinical trials, but displayed limited therapeutic benefit. …”
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Multicentre Harmonisation of a Six-Colour Flow Cytometry Panel for Naïve/Memory T Cell Immunomonitoring by Iole Macchia, Valentina La Sorsa, Irene Ruspantini, Massimo Sanchez, Valentina Tirelli, Maria Carollo, Giorgio Fedele, Pasqualina Leone, Giovanna Schiavoni, Carla Buccione, Paola Rizza, Paola Nisticò, Belinda Palermo, Stefania Morrone, Helena Stabile, Aurelia Rughetti, Marianna Nuti, Ilaria Grazia Zizzari, Cinzia Fionda, Roberta Maggio, Cristina Capuano, Concetta Quintarelli, Matilde Sinibaldi, Chiara Agrati, Rita Casetti, Andrea Rozo Gonzalez, Floriana Iacobone, Angela Gismondi, Filippo Belardelli, Mauro Biffoni, Francesca Urbani

“…The panel was based on a backbone mixture of dried antibodies (anti-CD3, anti-CD4, anti-CD8, anti-CD45RA, and anti-CCR7) to detect naïve/memory T cells, recognised as potential prognostic/predictive immunological biomarkers in cancer immunotherapies. The coordinating centre distributed frozen peripheral blood mononuclear cells (PBMCs) and fresh whole blood (WB) samples from healthy donors, reagents, and Standard Operating Procedures (SOPs) to participants who performed experiments by their own equipment, in order to mimic a real-life scenario. …”
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Differential Regulation of NK Cell Receptors in Acute Lymphoblastic Leukemia by Le Jie Lee, Norfarazieda Hassan, Siti Zuleha Idris, Suresh Kumar Subbiah, Heng Fong Seow, Norhafizah Mohtaruddin, Kian Meng Chang, Raudhawati Osman, Hishamshah Mohd Ibrahim, Sheila Nathan, Maha Abdullah

“…Cancer immunotherapies are preferred over conventional treatments which are highly cytotoxic to normal cells. …”
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FLT3 is associated with dendritic cell infiltration, tertiary lymphoid structure construction, and predict response to checkpoint inhibitors immunotherapy in solid cancers by Yongchang Tang, Hong Wang, Jiankun Zhang, Chunhui Yang, Fei Xu, Yan Song, Tianen Li, Qiangbo Zhang

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Deciphering molecular and cellular ex vivo responses to bispecific antibodies PD1-TIM3 and PD1-LAG3 in human tumors by Alfred Zippelius, Petra Herzig, Pratiksha Gulati, Christian Klein, Marta Trüb, Kirsten D Mertz, Robert Rosenberg, Viola Heinzelmann-Schwarz, Mark Wiese, Didier Lardinois, Pablo Umana, Marina Natoli, Klas Hatje, Fabian Junker, Zhiwen Jiang, Iakov I Davydov, Markus Germann, Daniel Marbach, Adrian Zwick, Patrick Weber, Stefan Seeber, Lothar Tietze, Laura Codarri-Deak, Henry Kao

“…Background Next-generation cancer immunotherapies are designed to broaden the therapeutic repertoire by targeting new immune checkpoints including lymphocyte-activation gene 3 (LAG-3) and T cell immunoglobulin and mucin-domain containing-3 (TIM-3). …”
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Targeting HVEM-GPT2 axis: a novel approach to T cell activation and metabolic reprogramming in non-small cell lung cancer therapy by Yuanshan Yao, Chunji Chen, Bin Li, Wen Gao

“…Abstract Background The modulation of tumor microenvironments through immune checkpoint pathways is pivotal for the development of effective cancer immunotherapies. This study aims to explore the role of HVEM in non-small cell lung cancer (NSCLC) microenvironment. …”
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Extracellular HMGB1 blockade inhibits tumor growth through profoundly remodeling immune microenvironment and enhances checkpoint inhibitor-based immunotherapy by Coraline Radermecker, Pascale Hubert, Patrick Roncarati, Stephanie Demoulin, Charlotte Pilard, Marie Ancion, Celia Reynders, Thomas Lerho, Diane Bruyere, Alizee Lebeau, Margot Meunier, Marie-Julie Nokin, Elodie Hendrick, Olivier Peulen, Philippe Delvenne, Michael Herfs

“…We also reported that a significant fraction of HMGB1 encountered within cancer microenvironment (interstitial fluids) is oxidized and, in opposite to its reduced isoform, oxidized HMGB1 acts as a tolerogenic signal in a receptor for advanced glycation endproducts-dependent manner.Conclusion Collectively, we present evidence that extracellular HMGB1 blockade may complement first-generation cancer immunotherapies by remobilizing antitumor immune response.…”
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Comparison of PD-L1 tumor cell expression with 22C3, 28-8, and SP142 IHC assays across multiple tumor types by Jeffrey S Ross, Richard S P Huang, Jake G Maule, Lani K Clinton, Ryon P Graf, Jinpeng Xiao, Geoffrey R Oxnard

“…Background Multiple PD-L1 immunohistochemistry (IHC) assays, including DAKO 22C3, DAKO 28-8, and Ventana SP142 PD-L1 IHC assays, have been approved by the Food and Drug Administration as a companion diagnostic (CDx) for various antiprogrammed death-1 and antiprogrammed death ligand 1 (PD-L1) based cancer immunotherapies. Here we present 22C3, 28-8, and SP142 analysis of 418 tumor specimens encountered in routine clinical practice.Methods All specimens were tested with 22C3, 28-8, and SP142 assays following the manufacturer’s established staining protocols.Results The same PD-L1 status (defined as tumor cell expression (TC) scores with all three assays ≥1% or all <1%) was observed in 60.0% (251/418) tumor specimens (45.9% (192/418) were triple negative and 14.1% (59/418) were triple positive). …”
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