CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer
Kipp Weiskopf,Nadine Jahchan,Peter J. Schnorr,Sandra Cristea,Aaron M. Ring,Roy Louis Maute,Anne Kathrin Volkmer,Jens Peter Volkmer,Jie Liu,Jing Shan Lim,Dian Yang,Garrett Seitz,Thuyen Nguyen,Di Wu,Kevin Jude,Heather Guerston,Amira A. Barkal,Francesca Trapani,Julie George,John T. Poirier,Eric E. Gardner,Linde A. Miles,Elisa de Stanchina,Shane Lofgren,Hannes Vogel,Monte M. Winslow,Caroline Dive,Roman K. Thomas,Charles M. Rudin,Matt van de Rijn,Ravindra Majeti,K. Christopher Garcia,Irving L. Weissman,Julien Sage +33 more
Reads0
Chats0
TLDR
Disruption of the interaction of CD47 with SIRPα using anti-CD47 antibodies induced macrophage-mediated phagocytosis of human SCLC patient cells in culture, and this approach could enable personalized immunotherapeutic regimens in patients with S CLC and other cancers.Abstract:
Small-cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer with limited treatment options. CD47 is a cell-surface molecule that promotes immune evasion by engaging signal-regulatory protein alpha (SIRPα), which serves as an inhibitory receptor on macrophages. Here, we found that CD47 is highly expressed on the surface of human SCLC cells; therefore, we investigated CD47-blocking immunotherapies as a potential approach for SCLC treatment. Disruption of the interaction of CD47 with SIRPα using anti-CD47 antibodies induced macrophage-mediated phagocytosis of human SCLC patient cells in culture. In a murine model, administration of CD47-blocking antibodies or targeted inactivation of the Cd47 gene markedly inhibited SCLC tumor growth. Furthermore, using comprehensive antibody arrays, we identified several possible therapeutic targets on the surface of SCLC cells. Antibodies to these targets, including CD56/neural cell adhesion molecule (NCAM), promoted phagocytosis in human SCLC cell lines that was enhanced when combined with CD47-blocking therapies. In light of recent clinical trials for CD47-blocking therapies in cancer treatment, these findings identify disruption of the CD47/SIRPα axis as a potential immunotherapeutic strategy for SCLC. This approach could enable personalized immunotherapeutic regimens in patients with SCLC and other cancers.read more
Citations
More filters
Journal ArticleDOI
Targeting macrophages: therapeutic approaches in cancer.
TL;DR: The state of the art of TAM-targeting strategies is evaluated, focusing on the limitations and potential side effects of the different therapies such as toxicity, rebound effects and compensatory mechanisms.
Journal ArticleDOI
Small-cell lung cancer: what we know, what we need to know and the path forward
TL;DR: Over the past 5 years, there has been a worldwide resurgence of studies on SCLC, including comprehensive molecular analyses, the development of relevant genetically engineered mouse models and the establishment of patient-derived xenografts, which have led to the discovery of new potential therapeutic vulnerabilities for SCLc and therefore to new clinical trials.
Journal ArticleDOI
Tumor-associated macrophages: an accomplice in solid tumor progression
TL;DR: The role of TAMs in promoting tumor growth, enhancing cancer cells resistance to chemotherapy and radiotherapy, promoting tumor angiogenesis, inducing tumor migration and invasion and metastasis, activating immunosuppression is focused on.
Journal ArticleDOI
Phagocytosis checkpoints as new targets for cancer immunotherapy.
TL;DR: An improved understanding of the tumour-intrinsic processes that inhibit essential immune surveillance processes, such as phagocytosis and innate immune sensing, could pave the way for the development of highly effective combination immunotherapy strategies that modulate both innate and adaptive antitumour immune responses.
Journal ArticleDOI
Small-cell lung cancer.
TL;DR: The recent introduction of immune checkpoint blockade into the treatment of patients with small-cell lung cancer (SCLC) is offering new hope, with a small subset of patients deriving prolonged benefit.
References
More filters
Journal ArticleDOI
The blockade of immune checkpoints in cancer immunotherapy
TL;DR: Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
Journal ArticleDOI
Signatures of mutational processes in human cancer
Ludmil B. Alexandrov,Serena Nik-Zainal,Serena Nik-Zainal,David C. Wedge,Samuel Aparicio,Sam Behjati,Sam Behjati,Andrew V. Biankin,Graham R. Bignell,Niccolo Bolli,Niccolo Bolli,Åke Borg,Anne Lise Børresen-Dale,Anne Lise Børresen-Dale,Sandrine Boyault,Birgit Burkhardt,Adam Butler,Carlos Caldas,Helen Davies,Christine Desmedt,Roland Eils,Jorunn E. Eyfjord,John A. Foekens,Mel Greaves,Fumie Hosoda,Barbara Hutter,Tomislav Ilicic,Sandrine Imbeaud,Sandrine Imbeaud,Marcin Imielinsk,Natalie Jäger,David T. W. Jones,David T. Jones,Stian Knappskog,Stian Knappskog,Marcel Kool,Sunil R. Lakhani,Carlos López-Otín,Sancha Martin,Nikhil C. Munshi,Nikhil C. Munshi,Hiromi Nakamura,Paul A. Northcott,Marina Pajic,Elli Papaemmanuil,Angelo Paradiso,John V. Pearson,Xose S. Puente,Keiran Raine,Manasa Ramakrishna,Andrea L. Richardson,Andrea L. Richardson,Julia Richter,Philip Rosenstiel,Matthias Schlesner,Ton N. Schumacher,Paul N. Span,Jon W. Teague,Yasushi Totoki,Andrew Tutt,Rafael Valdés-Mas,Marit M. van Buuren,Laura van ’t Veer,Anne Vincent-Salomon,Nicola Waddell,Lucy R. Yates,Icgc PedBrain,Jessica Zucman-Rossi,Jessica Zucman-Rossi,P. Andrew Futreal,Ultan McDermott,Peter Lichter,Matthew Meyerson,Matthew Meyerson,Sean M. Grimmond,Reiner Siebert,Elias Campo,Tatsuhiro Shibata,Stefan M. Pfister,Stefan M. Pfister,Peter J. Campbell,Peter J. Campbell,Peter J. Campbell,Michael R. Stratton,Michael R. Stratton +84 more
TL;DR: It is shown that hypermutation localized to small genomic regions, ‘kataegis’, is found in many cancer types, and this results reveal the diversity of mutational processes underlying the development of cancer.
Journal ArticleDOI
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
Jordi Barretina,Giordano Caponigro,Nicolas Stransky,Kavitha Venkatesan,Adam A. Margolin,Adam A. Margolin,Sungjoon Kim,Christine D. Wilson,Joseph Lehar,Gregory V. Kryukov,Dmitriy Sonkin,Anupama Reddy,Manway Liu,Lauren Murray,Michael F. Berger,Michael F. Berger,John Monahan,Paula Morais,Jodi Meltzer,Adam Korejwa,Judit Jané-Valbuena,Judit Jané-Valbuena,Felipa A. Mapa,Joseph Thibault,Eva Bric-Furlong,Pichai Raman,Aaron Shipway,Ingo H. Engels,Jill Cheng,Guoying K. Yu,Jianjun Yu,Peter Aspesi,Melanie de Silva,Kalpana Jagtap,Michael D. Jones,Li Wang,Charlie Hatton,Emanuele Palescandolo,Supriya Gupta,Scott Mahan,Carrie Sougnez,Robert C. Onofrio,Ted Liefeld,Laura E. MacConaill,Wendy Winckler,Michael R. Reich,Nanxin Li,Jill P. Mesirov,Stacey Gabriel,Gad Getz,Kristin G. Ardlie,Vivien W. Chan,Vic E. Myer,Barbara L. Weber,Jeffrey A. Porter,Markus Warmuth,Peter Finan,Jennifer L. Harris,Matthew Meyerson,Matthew Meyerson,Todd R. Golub,Michael Morrissey,William R. Sellers,Robert Schlegel,Levi A. Garraway,Levi A. Garraway +65 more
TL;DR: The results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents and the generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of ‘personalized’ therapeutic regimens.
Journal ArticleDOI
Macrophage plasticity and polarization: in vivo veritas
Antonio Sica,Alberto Mantovani +1 more
TL;DR: The identification of mechanisms and molecules associated with macrophage plasticity and polarized activation provides a basis for Macrophage-centered diagnostic and therapeutic strategies.
Journal ArticleDOI
Macrophage Activation and Polarization: Nomenclature and Experimental Guidelines
Peter J. Murray,Judith E. Allen,Subhra K. Biswas,Edward A. Fisher,Derek W. Gilroy,Sergij Goerdt,Siamon Gordon,John A. Hamilton,Lionel B. Ivashkiv,Toby Lawrence,Massimo Locati,Alberto Mantovani,Fernando O. Martinez,Jean-Louis Mege,David M. Mosser,Gioacchino Natoli,Jeroen P. J. Saeij,Joachim L. Schultze,Kari Ann Shirey,Antonio Sica,Jill Suttles,Irina A. Udalova,Jo A. Van Ginderachter,Stefanie N. Vogel,Thomas A. Wynn +24 more
TL;DR: A set of standards encompassing three principles-the source of macrophages, definition of the activators, and a consensus collection of markers to describe macrophage activation are described with the goal of unifying experimental standards for diverse experimental scenarios.
Related Papers (5)
The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors
Stephen B. Willingham,Jens Peter Volkmer,Andrew J. Gentles,Debashis Sahoo,Piero Dalerba,Siddhartha Mitra,Jian Wang,Humberto Contreras-Trujillo,Robin Martin,Justin D. Cohen,Patricia Lovelace,Ferenc A. Scheeren,Mark P. Chao,Kipp Weiskopf,Chad Tang,Anne Kathrin Volkmer,Tejaswitha J. Naik,Theresa A. Storm,Adriane Mosley,Badreddin Edris,Seraina Schmid,Chris K. Sun,Mei-Sze Chua,Oihana Murillo,Pradeep S. Rajendran,Adriel C. Cha,Robert K. Chin,Dongkyoon Kim,Maddalena Adorno,Tal Raveh,Diane Tseng,Siddhartha Jaiswal,Per Øyvind Enger,Gary K. Steinberg,Gordon Li,Samuel So,Ravindra Majeti,Griffith R. Harsh,Matt De Van Rijn,Nelson N.H. Teng,John B. Sunwoo,Ash A. Alizadeh,Michael F. Clarke,Irving L. Weissman +43 more
Anti-CD47 Antibody Synergizes with Rituximab to Promote Phagocytosis and Eradicate Non-Hodgkin Lymphoma
Mark P. Chao,Ash A. Alizadeh,Chad Tang,June Helen Myklebust,June Helen Myklebust,Bindu Varghese,Saar Gill,Max Jan,Adriel C. Cha,Charles Chan,Brent T. Tan,Christopher Y. Park,Feifei Zhao,Holbrook E Kohrt,Raquel Malumbres,Javier Briones,Randy D. Gascoyne,Izidore S. Lossos,Ronald Levy,Irving L. Weissman,Ravindra Majeti +20 more