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immune-checkpoint blockade

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https://www.readbyqxmd.com/read/28077173/is-cd47-an-innate-immune-checkpoint-for-tumor-evasion
#1
REVIEW
Xiaojuan Liu, Hyunwoo Kwon, Zihai Li, Yang-Xin Fu
Cluster of differentiation 47 (CD47) (also known as integrin-associated protein) is a ubiquitously expressed glycoprotein of the immunoglobulin superfamily that plays a critical role in self-recognition. Various solid and hematologic cancers exploit CD47 expression in order to evade immunological eradication, and its overexpression is clinically correlated with poor prognoses. One essential mechanism behind CD47-mediated immune evasion is that it can interact with signal regulatory protein-alpha (SIRPα) expressed on myeloid cells, causing phosphorylation of the SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition motifs and recruitment of Src homology 2 domain-containing tyrosine phosphatases to ultimately result in delivering an anti-phagocytic-"don't eat me"-signal...
January 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28070598/advanced-mri-assessment-to-predict-benefit-of-anti-programmed-cell-death-1-protein-immunotherapy-response-in-patients-with-recurrent-glioblastoma
#2
Lei Qin, Xiang Li, Amanda Stroiney, Jinrong Qu, Jeffrey Helgager, David A Reardon, Geoffrey S Young
INTRODUCTION: We describe the imaging findings encountered in GBM patients receiving immune checkpoint blockade and assess the potential of quantitative MRI biomarkers to differentiate patients who derive therapeutic benefit from those who do not. METHODS: A retrospective analysis was performed on longitudinal MRIs obtained on recurrent GBM patients enrolled on clinical trials. Among 10 patients with analyzable data, bidirectional diameters were measured on contrast enhanced T1 (pGd-T1WI) and volumes of interest (VOI) representing measurable abnormality suggestive of tumor were selected on pGdT1WI (pGdT1 VOI), FLAIR-T2WI (FLAIR VOI), and ADC maps...
January 9, 2017: Neuroradiology
https://www.readbyqxmd.com/read/28070553/predicted-neoantigen-load-in-non-hypermutated-endometrial-cancers-correlation-with-outcome-and-tumor-specific-genomic-alterations
#3
Sachet A Shukla, Brooke E Howitt, Catherine J Wu, Panagiotis A Konstantinopoulos
Elevated neoantigen load has been previously correlated with improved outcome and response to immune checkpoint blockade in various tumor types. In endometrial cancer, previous studies of neoantigen load prediction have shown that the hypermutated MSI and POLE-mutated tumors harbor significantly higher predicted neoantigen load compared to the hypomutated CN-low/endometrioid and CN-high/serous-like tumors. Here, we report that predicted neoantigen load may be a prognostic factor in hypomutated endometrial cancers, both in CN-low/endometrioid and CN-high/serous-like tumors...
February 2017: Gynecologic Oncology Reports
https://www.readbyqxmd.com/read/28064556/pd-1-checkpoint-blockade-alone-or-combined-pd-1-and-ctla-4-blockade-as-immunotherapy-for-lung-cancer
#4
Tawee Tanvetyanon, Jhanelle E Gray, Scott J Antonia
Signaling through T-cell surface, an immune checkpoint protein such as PD-1 or CTLA-4 helps dampen or terminate unwanted immune responses. Blocking a single immune checkpoint or multiple checkpoints simultaneously can generate anti-tumor activity against a variety of cancers including lung cancer. Area covered: This review highlights the results of recent clinical studies of single or combination checkpoint inhibitor immunotherapy in non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). The authors discuss pembrolizumab and pembrolizumab plus ipilimumab, durvalumab and durvalumab plus tremelimumab, nivolumab and nivolumab plus ipilimumab for NSCLC as well as nivolumab and nivolumab plus ipilimumab for SCLC...
January 9, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28057932/dynamic-versus-static-biomarkers-in-cancer-immune-checkpoint-blockade-unravelling-complexity
#5
W Joost Lesterhuis, Anthony Bosco, Michael J Millward, Michael Small, Anna K Nowak, Richard A Lake
Recently, there has been a coordinated effort from academic institutions and the pharmaceutical industry to identify biomarkers that can predict responses to immune checkpoint blockade in cancer. Several biomarkers have been identified; however, none has reliably predicted response in a sufficiently rigorous manner for routine use. Here, we argue that the therapeutic response to immune checkpoint blockade is a critical state transition of a complex system. Such systems are highly sensitive to initial conditions, and critical transitions are notoriously difficult to predict far in advance...
January 6, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28057180/utilisation-des-inhibiteurs-de-pd-1-dans-les-h%C3%A3-mopathies-lympho%C3%A3-des
#6
Laura Bounaix, Mohammed Bendouda, Jacques-Olivier Bay, Richard Lemal
ANTI-PD-1 ANTIBODIES THERAPEUTIC USE IN LYMPHOID NEOPLASMS: Immune checkpoints blockade is under investigation in oncology, and has demonstrated its clinical efficacy. In hematology, immune checkpoints blockade is in earlier stages of development, but there are strong evidences of PD-1 blockade anti-tumor efficacy in some lymphoid malignancies. In this review, we will discuss the main clinical results of PD-1 inhibitors in lymphoid neoplasms and the main perspectives of development.
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28055269/targeting-pd-1-pathway-a-new-hope-for-gastrointestinal-cancers
#7
Burak Bilgin, Mehmet An Sendur, Muhammed Bülent Akıncı, Didem Şener Dede, Bülent Yalçın
BACKGROUND: VEGF, HER2 and EGFR targeted agents are currently used in gastric, esophageal and colorectal cancers. However, treatment outcomes are still poor in most of the Gastrointestinal (GI) cancers. Immune checkpoints are one of the most promising immunotherapy approaches. In this review article, we aimed to discuss the efficacy and safety of anti-PD-1/PD-L1 therapies in GI cancers, including gastric, esophageal and colorectal cancer in the era of published or reported recent studies...
January 5, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28052254/pan-cancer-immunogenomic-analyses-reveal-genotype-immunophenotype-relationships-and-predictors-of-response-to-checkpoint-blockade
#8
Pornpimol Charoentong, Francesca Finotello, Mihaela Angelova, Clemens Mayer, Mirjana Efremova, Dietmar Rieder, Hubert Hackl, Zlatko Trajanoski
The Cancer Genome Atlas revealed the genomic landscapes of human cancers. In parallel, immunotherapy is transforming the treatment of advanced cancers. Unfortunately, the majority of patients do not respond to immunotherapy, making the identification of predictive markers and the mechanisms of resistance an area of intense research. To increase our understanding of tumor-immune cell interactions, we characterized the intratumoral immune landscapes and the cancer antigenomes from 20 solid cancers and created The Cancer Immunome Atlas (https://tcia...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28049579/tumour-infiltrating-lymphocytes-and-the-emerging-role-of-immunotherapy-in-breast-cancer
#9
Stephen J Luen, Peter Savas, Stephen B Fox, Roberto Salgado, Sherene Loi
Breast cancer has not previously been considered a highly immunogenic cancer. Observations of tumour-infiltrating lymphocytes (TILs) in and around neoplastic cells in tumour samples, and associations with improved pathological complete response and clinical survival end points have changed our perspective on this. Lymphocytic infiltrates have long been observed in breast cancer; however, more recently, retrospective analysis of prospectively collected tissue samples from clinical trials has demonstrated the potential role of host immunosurveillance in influencing the biology of breast cancer...
December 31, 2016: Pathology
https://www.readbyqxmd.com/read/28049484/a-new-insight-in-chimeric-antigen-receptor-engineered-t-cells-for-cancer-immunotherapy
#10
REVIEW
Erhao Zhang, Hanmei Xu
Adoptive cell therapy using chimeric antigen receptor (CAR)-engineered T cells has emerged as a very promising approach to combating cancer. Despite its ability to eliminate tumors shown in some clinical trials, CAR-T cell therapy involves some significant safety challenges, such as cytokine release syndrome (CRS) and "on-target, off-tumor" toxicity, which is related to poor control of the dose, location, and timing of T cell activity. In the past few years, some strategies to avoid the side effects of CAR-T cell therapy have been reported, including suicide gene, inhibitory CAR, dual-antigen receptor, and the use of exogenous molecules as switches to control the CAR-T cell functions...
January 3, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28042031/chemoimmunotherapy-by-combining-oxaliplatin-with-immune-checkpoint-blockades-reduced-tumor-burden-in-colorectal-cancer-animal-model
#11
Weiwei Wang, Ling Wu, Jiansheng Zhang, Huiguo Wu, Enkun Han, Qiang Guo
BACKGROUND: Colorectal cancer (CRC) is among one of the top common cancers worldwide. Developing novel comprehensive treatment strategies is critical for improving survival of late stage CRC patients. Recent advances in immune checkpoint blockades provided a novel strategy for treating cancers via stimulating the antitumor immune response. However, the effects of immune checkpoint blockades were limited in CRC due to intrinsic resistance. Oxaliplatin (OXA) based chemotherapy was the foundation of CRC adjuvant chemotherapy...
December 29, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28039262/potential-predictive-value-of-tp53-and-kras-mutation-status-for-response-to-pd-1-blockade-immunotherapy-in-lung-adenocarcinoma
#12
Zhong-Yi Dong, Wenzhao Zhong, Xu-Chao Zhang, Jian Su, Zhi Xie, Si-Yang Liu, Hai-Yan Tu, Hua-Jun Chen, Yue-Li Sun, Qing Zhou, Jinji Yang, Xuening Yang, Jia-Xin Lin, Honghong Yan, Hao-Ran Zhai, Li-Xu Yan, Ri-Qiang Liao, Si-Pei Wu, Yi-Long Wu
PURPOSE: Although clinical studies have shown promise for targeting programmed cell death protein-1 (PD-1) and ligand (PD-L1) signaling in non-small cell lung cancer (NSCLC), the factors that predict which subtype patients will be responsive to checkpoint blockade are not fully understood. EXPERIMENTAL DESIGN: We performed an integrated analysis on the multiple-dimensional data types including genomic, transcriptomic, proteomic and clinical data from cohorts of lung adenocarcinoma public (Discovery Set) and internal (Validation Set) database and immunotherapeutic patients...
December 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28031229/t-cell-repertoire-diversification-is-associated-with-immune-related-toxicities-following-ctla-4-blockade-in-cancer-patients
#13
Lawrence Fong, David Y Oh, Jason Cham, Li Zhang, Grant Fong, Serena S Kwek, Mark Klinger, Malek Faham
Immune checkpoint inhibitors can induce clinical responses with many cancers but also immune-related adverse events (IRAEs). Mechanisms driving IRAEs are unknown. Because CTLA-4 blockade leads to proliferation of circulating T cells, we examined whether ipilimumab leads to clonal expansion of tissue-reactive T cells. Rather than narrowing the T cell repertoire to a limited number of clones, ipilimumab induced greater repertoire diversification in IRAE patients compared to patients without IRAEs, with increases in the numbers of clonotypes, including newly detected clones, and declines in T cell clonality overall...
December 28, 2016: Cancer Research
https://www.readbyqxmd.com/read/28031159/evolution-of-neoantigen-landscape-during-immune-checkpoint-blockade-in-non-small-cell-lung-cancer
#14
Valsamo Anagnostou, Kellie N Smith, Patrick M Forde, Noushin Niknafs, Rohit Bhattacharya, James White, Theresa Zhang, Vilmos Adleff, Jillian Phallen, Neha Wali, Carolyn Hruban, Violeta B Guthrie, Kristen Rodgers, Jarushka Naidoo, Hyunseok Kang, William H Sharfman, Christos Georgiades, Franco Verde, Peter Illei, Qing Kay Li, Edward Gabrielson, Malcolm V Brock, Cynthia A Zahnow, Stephen B Baylin, Robert Scharpf, Julie R Brahmer, Rachel Karchin, Drew M Pardoll, Victor E Velculescu
Immune checkpoint inhibitors have shown significant therapeutic responses against tumors containing increased mutation-associated neoantigen load. We have examined the evolving landscape of tumor neoantigens during the emergence of acquired resistance in non-small cell lung cancer patients after initial response to immune checkpoint blockade with anti-PD1 or anti-PD-1/anti-CTLA4 antibodies. Analyses of matched pretreatment and resistant tumors identified genomic changes resulting in loss of 7 to 18 putative mutation-associated neoantigens in resistant clones...
December 28, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/28030901/radiotherapy-and-immune-checkpoint-blockades-a-snapshot-in-2016
#15
REVIEW
Taeryool Koo, In Ah Kim
Immune checkpoint blockades including monoclonal antibodies (mAbs) of cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) have been emerged as a promising anticancer therapy. Several immune checkpoint blockades have been approved by US Food and Drug Administration (FDA), and have shown notable success in clinical trials for patients with advanced melanoma and non-small cell lung cancer. Radiotherapy is a promising combination partner of immune checkpoint blockades due to its potent pro-immune effect...
December 2016: Radiation Oncology Journal
https://www.readbyqxmd.com/read/28025978/immune-targets-and-neoantigens-for-cancer-immunotherapy-and-precision-medicine
#16
REVIEW
Rong-Fu Wang, Helen Y Wang
Harnessing the immune system to eradicate malignant cells is becoming a most powerful new approach to cancer therapy. FDA approval of the immunotherapy-based drugs, sipuleucel-T (Provenge), ipilimumab (Yervoy, anti-CTLA-4), and more recently, the programmed cell death (PD)-1 antibody (pembrolizumab, Keytruda), for the treatment of multiple types of cancer has greatly advanced research and clinical studies in the field of cancer immunotherapy. Furthermore, recent clinical trials, using NY-ESO-1-specific T cell receptor (TCR) or CD19-chimeric antigen receptor (CAR), have shown promising clinical results for patients with metastatic cancer...
January 2017: Cell Research
https://www.readbyqxmd.com/read/28018970/interlesional-diversity-of-t-cell-receptors-in-melanoma-with-immune-checkpoints-enriched-in-tissue-resident-memory-t-cells
#17
Chandra Sekhar Boddupalli, Noffar Bar, Krishna Kadaveru, Michael Krauthammer, Natopol Pornputtapong, Zifeng Mai, Stephan Ariyan, Deepak Narayan, Harriet Kluger, Yanhong Deng, Rakesh Verma, Rituparna Das, Antonella Bacchiocchi, Ruth Halaban, Mario Sznol, Madhav V Dhodapkar, Kavita M Dhodapkar
Heterogeneity of tumor cells and their microenvironment can affect outcome in cancer. Blockade of immune checkpoints (ICPs) expressed only on a subset of immune cells leads to durable responses in advanced melanoma. Tissue-resident memory T (TRM) cells have recently emerged as a distinct subset of memory T cells in nonlymphoid tissues. Here, we show that functional properties and expression of ICPs within tumor-infiltrating lymphocytes (TILs) differ from those of blood T cells. TILs secrete less IL-2, IFN-γ, and TNF-α compared with circulating counterparts, and expression of VEGF correlated with reduced TIL infiltration...
December 22, 2016: JCI Insight
https://www.readbyqxmd.com/read/28007774/combined-kit-and-ctla-4-blockade-in-patients-with-refractory-gist-and-other-advanced-sarcomas-a-phase-ib-study-of-dasatinib-plus-ipilimumab
#18
Sandra P D'Angelo, Alexander N Shoushtari, Mary Louise Keohan, Mark A Dickson, Mrinal M Gounder, Ping Chi, Jennifer K Loo, Leigh Gaffney, Lee Schneider, Zarine Patel, Joseph P Erinjeri, Mark Bluth, Ana Sjoberg, Howard Streicher, Naoko Takebe, Li-Xuan Qin, Cristina R Antonescu, Ronald P DeMatteo, Richard D Carvajal, William D Tap
PURPOSE: A phase Ib study of dasatinib plus ipilimumab in GIST and other sarcomas was performed based on pre-clinical data demonstrating that combined KIT and CTLA-4 blockade is synergistic. EXPERIMENTAL DESIGN: A standard 3+3 design was used evaluate the safety, efficacy and immune correlates of treatment. Dose escalation cohorts received ipilimumab 10 or 3 mg/kg every 3 weeks followed by maintenance every 12 weeks with escalating doses of dasatinib (70mg daily, 100 mg daily or 70 mg twice daily)...
December 22, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28004449/genomic-pathobiology-of-gastric-carcinoma
#19
Hiroto Katoh, Shumpei Ishikawa
With the recent advances in genome sequencing technologies, comprehensive cancer genomic profiling has revealed the in-depth molecular mechanisms of gastric malignancies. New insights into the carcinogenesis pathways of gastric cancers have been acquired, not only by DNA sequencing, but also by the expression profiling of the transcriptome, the identification of chimeric genes, and epi-genetic profiling (such as DNA hypermethylation). Global genomic profiling of gastric cancers, in combination with histopathology, etiology, and cancer biology, has clarified that gastric cancers can be categorized into four subtypes with specific genomic characteristics...
December 22, 2016: Pathology International
https://www.readbyqxmd.com/read/28003187/angiopoietin-2-as-a-biomarker-and-target-for-immune-checkpoint-therapy
#20
Xinqi Wu, Anita Giobbie-Hurder, Xiaoyun Liao, Courtney Connelly, Erin M Connolly, Jingjing Li, Michael P Manos, Donald Lawrence, David McDermott, Mariano Severgnini, Jun Zhou, Evisa Gjini, Ana Lako, Mikel Lipschitz, Christine J Pak, Sara Abdelrahman, Scott Rodig, F Stephen Hodi
Immune checkpoint therapies targeting CTLA-4 and PD-1 have proven effective in cancer treatment. However, the identification of biomarkers for predicting clinical outcomes and mechanisms to overcome resistance remain as critical needs. Angiogenesis is increasingly appreciated as an immune modulator with potential for combinatorial use with checkpoint blockade. Angiopoietin-2 (ANGPT2) is an immune target in patients and is involved in resistance to anti-VEGF treatment with the monoclonal antibody bevacizumab...
January 2017: Cancer Immunology Research
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