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immunotherapy biomarker

Denise Lau, Alexandria M Bobe, Aly A Khan
RNA sequencing (RNA-seq) provides an efficient high-throughput technique to robustly characterize the tumor immune microenvironment (TME). The increasing use of RNA-seq in clinical and basic science settings provides a powerful opportunity to access novel therapeutic biomarkers in the TME. Advanced computational methods are making it possible to resolve the composition of the tumor immune infiltrate, infer the immunological phenotypes of those cells, and assess the immune receptor repertoire in RNA-seq data...
March 2019: Trends in Cancer
Mark Yarchoan, Lee A Albacker, Alexander C Hopkins, Meagan Montesion, Karthikeyan Murugesan, Teena T Vithayathil, Neeha Zaidi, Nilofer S Azad, Daniel A Laheru, Garrett M Frampton, Elizabeth M Jaffee
BACKGROUND: PD-L1 expression and tumor mutational burden (TMB) have emerged as important biomarkers of response to immune checkpoint inhibitor (ICI) therapy. These biomarkers have each succeeded and failed in predicting responders for different cancer types. We sought to describe the PD-L1 expression landscape across the spectrum of ICI-responsive human cancers, and to determine the relationship between PD-L1 expression, TMB, and response rates to ICIs. METHODS: We assessed 9887 clinical samples for PD-L1 expression and TMB...
March 21, 2019: JCI Insight
Zhiqiang Chen, Xueliang Zuo, Liyong Pu, Yao Zhang, Guoyong Han, Long Zhang, Zhengshan Wu, Wei You, Jianjie Qin, Xinzheng Dai, Hongbing Shen, Xuehao Wang, Jindao Wu
OBJECTIVES: Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is a cancer/testis antigen reactivated in several human malignancies. So far, the major focus of studies on KK-LC-1 has been on its potential as diagnostic biomarker and immunotherapy target. However, its biological functions and molecular mechanisms in cancer progression remain unknown. MATERIALS AND METHODS: Expression of KK-LC-1 in HCC was analysed using RT-qPCR, Western blot and immunohistochemistry. The roles of KK-LC-1 on HCC progression were examined by loss-of-function and gain-of-function approaches...
March 20, 2019: Cell Proliferation
S Trebeschi, S G Drago, N J Birkbak, I Kurilova, A M Cǎlin, A Delli Pizzi, F Lalezari, D M J Lambregts, M Rohaan, C Parmar, K J Hartemink, C Swanton, J B A G Haanen, C U Blank, E F Smit, R G H Beets-Tan, H J W L Aerts
INTRODUCTION: Immunotherapy is regarded one of the major breakthroughs in cancer treatment. Despite its success, only a subset of patients responds - urging the quest for predictive biomarkers. We hypothesize that Artificial Intelligence (AI) algorithms can automatically quantify radiographic characteristics that are related to and may therefore act as non-invasive radiomic biomarkers for immunotherapy response. PATIENTS AND METHODS: In this study, we analyzed 1055 primary and metastatic lesions from 203 patients with advanced melanoma and non-small cell lung cancer (NSCLC) undergoing anti-PD1 therapy...
March 21, 2019: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Arseniy E Yuzhalin
Posttranslational modifications of proteins have been implicated in pathogenesis of numerous diseases. Arginine deimination (also known as citrullination) has a principal role in progression of rheumatoid arthritis through generation of autoantibodies and exacerbation of the inflammatory response. Recently, multiple research groups provided solid evidence of citrullination being in control of cancer progression; however, there is no comprehensive overview of these findings. This article summarizes and critically reviews the influence of citrullination on different aspects of tumor biology, including (i) regulation of apoptosis and differentiation, (ii) promoting EMT and metastasis, and (iii) potential use of citrullinated antigens for immunotherapy...
March 20, 2019: Cancer Research
Paolo Tarantino, Giuseppe Curigliano
In the phase III ImPassion130 trial the addition of immunotherapy to chemotherapy improved overall survival in mTNBC patients. This benefit was significant only in patients harboring PD-L1-positive tumors, suggesting that stratification according to response biomarkers is needed to achieve consistent responses. Besides PD-L1 expression, a variety of potential biomarkers are under investigation for predicting immunotherapy efficacy in breast cancer, such as tumor-infiltrating lymphocytes, gene signatures, tumor mutational burden, microsatellite instability and gut microbiome...
March 20, 2019: Expert Opinion on Biological Therapy
Berna C Özdemir, Gian-Paolo Dotto
The impact of sex hormones on anticancer immunity deserves attention due to the importance of the immune system in cancer therapy and the recognition of sex differences in immunity. Cancer is ultimately the result of failed immune surveillance and diverging effects of male and female sex hormones on anticancer immunity could contribute to the higher cancer incidence and poorer outcome in men. Estrogens and androgens affect the number and function of immune cells, an effect that depends on cell type, tumor microenvironment, and the age and reproductive status of the individual...
March 19, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Jun Gong, Alexander Chehrazi-Raffle, Veronica Placencio-Hickok, Michelle Guan, Andrew Hendifar, Ravi Salgia
There is growing interest in identifying predictive biomarkers for inhibitors of programmed cell death protein 1 receptor (PD-1), programmed death ligand 1 (PD-L1), and cytotoxic T-lymphocyte associated protein 4 (CTLA-4). Given the links between the stool microbiota, anticancer immunosurveillance, and general health, the composition of the gut microbiome has recently undergone investigation as a biomarker for immunotherapy. In this review, we highlight published results from preclinical and clinical studies to date supporting a relationship between the gut microbiome and antitumor efficacy of immune checkpoint inhibitors...
March 18, 2019: Clinical and Translational Medicine
Tiberiu Popescu, Ulf Karlsson, Vincent Vinh-Hung, Lurdes Trigo, Juliette Thariat, Te Vuong, Brigitta G Baumert, Micaela Motta, Alice Zamagni, Marta Bonet, Arthur Sun Myint, Pedro Carlos Lara, Nam P Nguyen, Meritxell Arenas
The management of older cancer patients remains difficult because of data paucity. Radiation oncologists need to identify potential issues which could affect treatment of those patients. A workshop was organized in Barcelona among international radiation oncologists with special interest in the management of older cancer patients on April 22, 2018. The following consensus was reached: 1. Older cancer patients often faced unconscious discriminating bias from cancer specialists and institutions because of their chronological age...
March 16, 2019: Cancers
Irene T Schrijver, Charlotte Théroude, Thierry Roger
Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells characterized by their immunosuppressive functions. MDSCs expand during chronic and acute inflammatory conditions, the best described being cancer. Recent studies uncovered an important role of MDSCs in the pathogenesis of infectious diseases along with sepsis. Here we discuss the mechanisms underlying the expansion and immunosuppressive functions of MDSCs, and the results of preclinical and clinical studies linking MDSCs to sepsis pathogenesis...
2019: Frontiers in Immunology
Katharine Margaret Irvine, Isanka Ratnasekera, Elizabeth E Powell, David Arthur Hume
Liver cirrhosis is an increasing health burden and public health concern. Regardless of etiology, patients with cirrhosis are at risk of a range of life-threatening complications, including the development of infections, which are associated with high morbidity and mortality and frequent hospital admissions. The term Cirrhosis-Associated Immune Dysfunction (CAID) refers to a dynamic spectrum of immunological perturbations that develop in patients with cirrhosis, which are intimately linked to the underlying liver disease, and negatively correlated with prognosis...
2019: Frontiers in Immunology
Leila Hadadi, Morteza Hafezi, Ali Akbar Amirzargar, Ramazan Ali Sharifian, Saeid Abediankenari, Hossein Asgarian-Omran
BACKGROUND: In this study, the expression pattern of NKp30 and T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3), as candidates for activating and inhibitory receptors of NK cells, were evaluated in patients with chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: 24 CLL patients and 19 healthy controls were enrolled. Fresh peripheral blood was collected from all subjects and stained with fluorochrome-conjugated antibodies. The frequency of CD56+/CD3-/NKp30+ and CD56+/CD3-/Tim-3+ cells was determined by multicolor flow cytometry...
March 14, 2019: Oncology Research and Treatment
Nikolaos F Pistamaltzian, Vassilis Georgoulias, Athanasios Kotsakis
Cancer immunotherapy represents a major therapeutic breakthrough. Immune checkpoint inhibitors alone or in the context of a combination are considered the new standard of care in advanced non-small cell lung cancer (NSCLC). Areas covered: This review explains the biologic rationale behind the implementation of immune checkpoint inhibitors for the therapy of advanced NSCLC. It provides a detailed description of the clinical trials that have studied the various agents now in use and the results that lead to the currently approved indications...
March 14, 2019: Expert Review of Respiratory Medicine
Anna Gajos-Michniewicz, Malgorzata Czyz
Tumour metastasis is a multistep process. Melanoma is a highly aggressive cancer and metastasis accounts for the majority of patient deaths. microRNAs (miRNAs) are non-coding RNAs that affect the expression of their target genes. When aberrantly expressed they contribute to the development of melanoma. While miRNAs can act locally in the cell where they are synthesized, they can also influence the phenotype of neighboring melanoma cells or execute their function in the direct tumour microenvironment by modulating ECM (extracellular matrix) and the activity of fibroblasts, endothelial cells, and immune cells...
March 7, 2019: Cancers
Peng Song, Jingcheng Zhang, Congcong Shang, Li Zhang
To summarize the therapeutic effects of PD-1/PD-L1 inhibitors on patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting, we attempted to identify potential molecular biomarkers or clinical factors that reflected the therapeutic effect. The medical records of patients with non-small cell lung cancer who were treated with PD-1/PD-L1 inhibitors were obtained from the outpatient department or inpatient department of Peking Union Medical College Hospital from August 1, 2015, to January 1, 2018...
March 12, 2019: Scientific Reports
Shichao Zhang, Erdong Zhang, Jinhua Long, Zuquan Hu, Jian Peng, Lina Liu, Fuzhou Tang, Long Li, Yan Ouyang, Zhu Zeng
Immune infiltration of tumours is closely associated with clinical outcome in renal cell carcinoma (RCC). Tumour-infiltrating immune cells (TIICs) regulate cancer progression and are appealing therapeutic targets. The purpose of this study was to determine the composition of TIICs in RCC and further reveal the independent prognostic values of TIICs. CIBERSORT, an established algorithm, was applied to estimate the proportions of 22 immune cell types based on gene expression profiles of 891 tumours. Cox regression was used to evaluate the association of TIICs and immune checkpoint modulators with overall survival (OS)...
March 12, 2019: Cancer Science
Yue Song, Zhaoming Li, Weili Xue, Mingzhi Zhang
The immune system is very important for monitoring and eradicating cancer cells. However, there may be multiple immunosuppressive mechanisms to prevent effective antitumor immunity in the tumor environment, such as the negative immunologic regulators known as checkpoints. Antibodies that block the checkpoints programmed cell death protein 1 (PD-1) pathway have made great success. Nevertheless, the response rates are likely to vary widely. Therefore, several researches are currently underway to determine which biomarkers are able to identify the group of patients who can obtain benefits from PD-1 and programmed cell death-ligand 1 (PD-L1) immune checkpoint blockade therapy...
April 2019: Immunotherapy
Patrick J Eulitt, Marc A Bjurlin, Matthew I Milowsky
PURPOSE OF REVIEW: Recent advances in research related to biomarkers and immunotherapy has the potential to transform the landscape for the use of perioperative systemic therapy in patients with bladder cancer. RECENT FINDINGS: Predictive biomarkers including DNA damage repair genes and gene expression profiling may soon lead to better selection of patients for neoadjuvant cisplatin-based chemotherapy. Success of immunotherapy for the treatment of metastatic bladder cancer has led to promising trials exploring immunotherapy in muscle-invasive disease...
March 6, 2019: Current Opinion in Urology
Shulun Chen, Zilan Song, Ao Zhang
Oncology immunotherapy has gained significant advances in recent years and benefits cancer patients with superior efficacy and superior clinical responses. Currently over ten immune checkpoint antibodies targeting CTLA-4 and PD-1/PD-L1 have received regulatory approval worldwide and over thousands are under active clinical trials. However, compared to the rapid advance of monoclonal antibody (mAb), studies on immunotherapeutic small molecules have far lagged behind. Small molecule immunotherapy not only can target immunosuppressive mechanisms similar to mAbs, but also can stimulate intracellular pathways downstream of checkpoint proteins in innate or adaptive immune cells that mAbs are unable to access...
March 8, 2019: Current Topics in Medicinal Chemistry
Åsa Kristina Öjlert, Ann Rita Halvorsen, Daniel Nebdal, Marius Lund-Iversen, Steinar Solberg, Odd Terje Brustugun, Ole Christian Lingjaerde, Åslaug Helland
The impact of the tumor immune microenvironment on overall survival in non-small cell lung cancer (NSCLC) has been studied, but there is little information on its relevance for risk of relapse after surgery. Understanding more about the immune microenvironment in previously untreated NSCLC could help in identifying high-risk patients and patients more likely to benefit from neoadjuvant/ adjuvant immunotherapy. Here, we examined gene expression in 399 surgically-derived NSCLC samples and 47 samples from normal lung, using Agilent microarray and RNA sequencing...
March 10, 2019: Molecular Oncology
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