Journal ArticleDOI
Immune Checkpoint Blockade in Cancer Immunotherapy: Mechanisms, Clinical Outcomes, and Safety Profiles of PD-1/PD-L1 Inhibitors.
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TLDR
This review clarifies the mechanisms of PD-1/PD-L1-mediated anti-cancer immune responses and some clinical studies of mAbs targeting PD-2/2/3/4/5/6 as well as the challenges and future of PD/L1 blockade therapy.Abstract:
Programmed cell death protein 1 (PD-1) and its ligand PD-L1 are critical for the regulation of T cell exhaustion and activity suppression. Tumor cells expressing immune checkpoints including PD-L1 escape monitoring of T cells from the host immune system. Checkpoint inhibitors are highly promising therapies that function as tumor-suppressing factors via modulation of tumor cell-immune cell interactions as well as boosting T cell-mediated anti-tumor immunity. Notably, PD-1 or PD-L1 monoclonal antibody (mAb) has demonstrated promising therapeutic effects in clinical studies of many types of cancer. These mAbs have caused significant tumor regression with impressive anti-tumor response rates as well as a favorable safety profile in cancer patients. Furthermore, the combination of PD-1/PD-L1 mAbs with other types of anti-tumor agents has also developed to boost the anti-tumor responses and enhance therapeutic effects in cancer patients. This review clarifies the mechanisms of PD-1/PD-L1-mediated anti-cancer immune responses and some clinical studies of mAbs targeting PD-1/PD-L1. The challenges and future of PD-1/PD-L1 blockade therapy are also discussed.read more
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Journal ArticleDOI
B Cell Function in the Tumor Microenvironment
TL;DR: The role of B cells in the TME is characterized in both animal models and patients, with an emphasis on dissecting how B cell heterogeneity contributes to the immune response to cancer.
Journal ArticleDOI
Small molecule inhibitors against PD-1/PD-L1 immune checkpoints and current methodologies for their development: a review.
TL;DR: In this article, the authors summarize the biophysical and biochemical assays currently employed for the measurements of binding capacities, molecular interactions, and blocking effects of small molecule inhibitors on PD-1/PD-L1.
Journal ArticleDOI
Crosstalk between angiogenesis and immune regulation in the tumor microenvironment
TL;DR: In this article , the authors investigated the crosstalk between immunity and angiogenesis in the tumor microenvironment (TME) and looked at strategies designed to enhance anti-cancer immunity, to convert suppressive tumors into immune activating tumors, and the mechanisms by which these strategies enhance effector immune cell infiltration.
Journal ArticleDOI
A clinically acceptable strategy for sensitizing anti-PD-1 treatment by hypoxia relief
Mengshi Jiang,Bing Qin,Lihua Luo,Xiang Li,Yingying Shi,Junlei Zhang,Zhenyu Luo,Chunqi Zhu,Guannan Guan,Yong-Zhong Du,Jian You +10 more
TL;DR: Wang et al. as discussed by the authors adopted three methods to alleviate hypoxia, including direct oxygen delivery using two different carriers and an indirect way involving HIF-1α inhibition, and they provided a good reference for improving the efficacy of PD-1 antibody by alleviating tumor hypoxide.
Journal Article
Emerging role of PD-L1 modification in cancer immunotherapy.
TL;DR: In this paper, the PD-L1 was reported to be acetylated at Lys263 site by p300 and was deacetylated by HDAC2, which led to a reduction of the nuclear portion of the programmed cell death protein.
References
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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
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
Suzanne L. Topalian,F. Stephen Hodi,Julie R. Brahmer,Scott N. Gettinger,David Smith,David F. McDermott,John D. Powderly,Richard D. Carvajal,Jeffrey A. Sosman,Michael B. Atkins,Philip D. Leming,David R. Spigel,Scott J. Antonia,Leora Horn,Charles G. Drake,Drew M. Pardoll,Lieping Chen,William H. Sharfman,Robert A. Anders,Janis M. Taube,Tracee L. McMiller,Haiying Xu,Alan J. Korman,Maria Jure-Kunkel,Shruti Agrawal,Dan McDonald,Georgia Kollia,Ashok Kumar Gupta,Jon M. Wigginton,Mario Sznol +29 more
TL;DR: Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use.
Journal ArticleDOI
Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer
Hossein Borghaei,Luis Paz-Ares,Leora Horn,D. R. Spigel,M. Steins,Neal Ready,L.Q. Chow,Everett E. Vokes,Enriqueta Felip,Esther Holgado,F. Barlesi,M. Kohlhufl,Oscar Arrieta,Marco Angelo Burgio,J. Fayette,H. Lena,Elena Poddubskaya,David E. Gerber,Scott N. Gettinger,Charles M. Rudin,Naiyer A. Rizvi,L. Crina,G. R. Blumenschein,Scott J. Antonia,C. Dorange,C. T. Harbison,F. Graf Finckenstein,Julie R. Brahmer +27 more
TL;DR: Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression (≥1, ≥5%, and ≥10%) of the PD-1 ligand.
Journal ArticleDOI
Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer
Julie R. Brahmer,Karen L. Reckamp,Paul Baas,Lucio Crinò,Wilfried Eberhardt,Elena Poddubskaya,Scott J. Antonia,Adam Pluzanski,Everett E. Vokes,Esther Holgado,David M. Waterhouse,Neal Ready,Justin F. Gainor,Osvaldo Arén Frontera,Libor Havel,Martin Steins,Marina Chiara Garassino,Joachim G.J.V. Aerts,Manuel Domine,Luis Paz-Ares,Martin Reck,Christine Baudelet,Christopher T. Harbison,Brian Lestini,David R. Spigel +24 more
TL;DR: Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level.
Journal ArticleDOI
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Dung T. Le,Jennifer N. Uram,Hao Wang,Bjarne Bartlett,Holly Kemberling,Aleksandra Eyring,Andrew D. Skora,Brandon Luber,Nilofer S. Azad,Daniel A. Laheru,Barbara A. Biedrzycki,Ross C. Donehower,Atif Zaheer,George A. Fisher,Todd S. Crocenzi,James J. Lee,Steven M. Duffy,Richard M. Goldberg,Richard M. Goldberg,Albert de la Chapelle,Albert de la Chapelle,Minori Koshiji,Feriyl Bhaijee,Thomas Huebner,Ralph H. Hruban,Laura D. Wood,Nathan Cuka,Drew M. Pardoll,Nickolas Papadopoulos,Kenneth W. Kinzler,Shibin Zhou,Toby C. Cornish,Janis M. Taube,Robert A. Anders,James R. Eshleman,Bert Vogelstein,Luis A. Diaz +36 more
TL;DR: This study showed that mismatch-repair status predicted clinical benefit of immune checkpoint blockade with pembrolizumab, and high somatic mutation loads were associated with prolonged progression-free survival.