PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome.
Hashem O. Alsaab,Hashem O. Alsaab,Samaresh Sau,Rami Alzhrani,Rami Alzhrani,Katyayani Tatiparti,Ketki Bhise,Sushil K. Kashaw,Sushil K. Kashaw,Arun K. Iyer,Arun K. Iyer +10 more
TLDR
The current landscape of the PD-1/PD-L1 mechanistic role in tumor immune evasion and therapeutic outcome for cancer treatment is reviewed and the current progress in clinical trials, combination of drug therapy with immunotherapy, safety, and future of check point inhibitors for multiple types of cancer are reviewed.Abstract:
Several cancers are highly refractory to conventional chemotherapy. The survival of tumors in several cases is assisted by checkpoint immunomodulation to maintain the imbalance between immune surveillance and cancer cell proliferation. Check point antibody inhibitors, such as anti-PD-1/PD-L1, are a novel class of inhibitors that function as a tumor suppressing factor via modulation of immune cell-tumor cell interaction. These checkpoint blockers are rapidly becoming a highly promising cancer therapeutic approach that yields remarkable antitumor responses with limited side effects. In recent times, more than four check point antibody inhibitors have been commercialized for targeting PD-1, PDL-1, and CTLA-4. Despite the huge success and efficacy of the anti-PD therapy response, it is limited to specific types of cancers, which attributes to the insufficient and heterogeneous expression of PD-1 in the tumor microenvironment. Herein, we review the current landscape of the PD-1/PD-L1 mechanistic role in tumor immune evasion and therapeutic outcome for cancer treatment. We also review the current progress in clinical trials, combination of drug therapy with immunotherapy, safety, and future of check point inhibitors for multiple types of cancer.read more
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Delivery technologies for cancer immunotherapy
TL;DR: How recent developments in drug delivery could enable new cancer immunotherapies and improve on existing ones are discussed, and the current delivery obstacles are examined.
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Three-Dimensional in Vitro Cell Culture Models in Drug Discovery and Drug Repositioning.
TL;DR: Common approaches to 3D culture are reviewed, the significance of 3D cultures in drug resistance and drug repositioning is discussed and some of the challenges of applying 3D cell cultures to high-throughput drug discovery are addressed.
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CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy
Amira A. Barkal,Rachel E. Brewer,Maxim Markovic,Mark Kowarsky,Sammy A. Barkal,Balyn W. Zaro,Venkatesh Krishnan,Jason Hatakeyama,Oliver Dorigo,Layla J. Barkal,Irving L. Weissman +10 more
TL;DR: CD24 interacts with the tumour-associated-macrophage receptor Siglec-10 to inhibit the macrophage-mediated clearance of cancer cells, revealing a new ‘don’t eat me’ signal as a potential target for cancer immunotherapy.
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Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors
TL;DR: Biomarkers reflecting tumor immune microenvironment and tumor cell intrinsic features, such as PD-L1 expression, density of tumor infiltrating lymphocyte (TIL), tumor mutational burden, and mismatch-repair (MMR) deficiency, have been noticed to associate with treatment effect of anti-PD-1/anti-PD.
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Management of Immunotherapy-Related Toxicities, Version 1.2019.
John A. Thompson,Bryan J. Schneider,Julie R. Brahmer,Stephanie Andrews,Philippe Armand,Shailender Bhatia,Lihua E. Budde,Luciano J. Costa,Marianne Davies,David Dunnington,Marc S. Ernstoff,Matthew J. Frigault,Brianna Hoffner,Christopher J. Hoimes,Mario E. Lacouture,Frederick L. Locke,Matthew A. Lunning,Nisha Mohindra,Jarushka Naidoo,Anthony J. Olszanski,Olalekan O. Oluwole,Sandip Pravin Patel,Sunil Reddy,Mabel Ryder,Bianca Santomasso,Scott Shofer,Jeffrey A. Sosman,Momen M. Wahidi,Yinghong Wang,Alyse Johnson-Chilla,Jillian L. Scavone +30 more
TL;DR: The content featured in this issue is an excerpt of the recommendations for managing toxicity related to immune checkpoint blockade and a review of existing evidence.
References
More filters
Journal ArticleDOI
Hallmarks of cancer: the next generation.
TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
Journal ArticleDOI
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma.
F. Stephen Hodi,Steven J. O'Day,David F. McDermott,R. W. Weber,Jeffrey A. Sosman,John B. A. G. Haanen,Rene Gonzalez,Caroline Robert,Dirk Schadendorf,Jessica C. Hassel,Wallace Akerley,Alfons J.M. van den Eertwegh,Jose Lutzky,Paul Lorigan,Julia Vaubel,Gerald P. Linette,David W. Hogg,Christian H. Ottensmeier,Céleste Lebbé,Christian Peschel,Ian Quirt,Joseph I. Clark,Jedd D. Wolchok,Jeffrey S. Weber,Jason Tian,Michael Yellin,Geoffrey M. Nichol,Axel Hoos,Walter J. Urba +28 more
TL;DR: Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma.
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
PD-1 blockade induces responses by inhibiting adaptive immune resistance
Paul C. Tumeh,Christina L. Harview,Jennifer H. Yearley,I. Peter Shintaku,Emma Taylor,Lidia Robert,Bartosz Chmielowski,Marko Spasic,Gina Henry,Voicu Ciobanu,Alisha N. West,Manuel Carmona,Christine Kivork,Elizabeth Seja,Grace Cherry,Antonio Gutierrez,Tristan Grogan,Christine Mateus,Gorana Tomasic,John A. Glaspy,Ryan O. Emerson,Harlan Robins,Robert H. Pierce,David Elashoff,Caroline Robert,Antoni Ribas +25 more
TL;DR: It is shown that pre-existing CD8+ T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy.
Journal ArticleDOI
Pembrolizumab for the treatment of non-small cell lung cancer
Edward B. Garon,Naiyer A. Rizvi,Rina Hui,Natasha B. Leighl,Ani Sarkis Balmanoukian,Joseph Paul Eder,Amita Patnaik,Charu Aggarwal,Matthew A. Gubens,Leora Horn,Enric Carcereny,Myung-Ju Ahn,Enriqueta Felip,Jong-Seok Lee,Matthew D. Hellmann,Omid Hamid,Jonathan W. Goldman,Jean-Charles Soria,Marisa Dolled-Filhart,Ruth Z. Rutledge,Jin Zhang,Jared Lunceford,Reshma A. Rangwala,Gregory M. Lubiniecki,Charlotte Roach,Kenneth Emancipator,Leena Gandhi +26 more
TL;DR: Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer and PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolIZumab.
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