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immunotherapy biomarker

Adrienne M Rothschilds, K Dane Wittrup
A plethora of new cancer immunotherapies are under clinical development individually and in combination for a wide variety of indications, but optimizing therapeutic outcomes will require precise consideration of timing in treatment schedule design. In this review, we summarize the current understanding of the temporal rhythms of the anticancer immune response. Lessons learned in preclinical and clinical studies begin to define a framework for incorporating duration and sequencing into immunotherapy. We also discuss key challenges and opportunities for translation of temporally programmed treatment schedules to the clinic, including alignment of immunological timescales in preclinical models and humans, and the use of current and emerging biomarkers...
December 10, 2018: Trends in Immunology
Yuzhen Wei, Haoxiao Chang, Xindi Li, Huabing Wang, Li Du, Heng Zhou, Wangshu Xu, Yuetao Ma, Linlin Yin, Xinghu Zhang
OBJECTIVE: We investigated the contribution of several cytokines in the pathogenesis of first-onset neuromyelitis optica spectrum disorder (NMOSD) and determined the differences between aquaporin 4 immunoglobulin G (AQP4-IgG)-positive and AQP4-IgG-negative subtypes. METHODS: We enrolled 18 NMOSD (10 AQP4-IgG-positive and 8 AQP4-IgG-negative) and 8 multiple sclerosis (MS) patients, whose serum and cerebrospinal fluid (CSF) samples were collected during the acute phase of the first onset before immunotherapy...
December 13, 2018: Neuroimmunomodulation
Francesca Battaglin, Madiha Naseem, Heinz-Josef Lenz, Mohamed E Salem
Microsatellite instability (MSI) is a key biomarker in colorectal cancer (CRC), with crucial diagnostic, prognostic, and predictive implications. Testing for mismatch repair deficiency (MMR-D)/MSI is recommended during screening for Lynch syndrome, an autosomal-dominant hereditary disease that is characterized by germline mutations in the MMR genes and associated with an increased risk for several types of cancer. Additionally, MSI-high (MSI-H) status is associated with a better prognosis in early-stage CRC and a lack of benefit from adjuvant treatment with 5-fluorouracil in stage II disease...
November 2018: Clinical Advances in Hematology & Oncology: H&O
Tomas Zemanek, Bohuslav Melichar, Martin Lovecek, Pavel Soucek, Beatrice Mohelnikova-Duchonova
Pancreatic carcinoma is usually diagnosed late when treatment options are limited and is considered a chemo-resistant malignancy. However, early stage, good performance status and specific patient subgroup are thought to have a more favorable prognosis. Search for novel molecular biomarkers, which could predict treatment resistance, represents a major opportunity, but also a challenge in further research. This review summarizes most aspects of individualized therapy of pancreatic cancer including promising biomarkers, BRCA-deficient pancreatic cancer and its etiology...
December 12, 2018: Pharmacogenomics
Lucia Masarova, Hagop Kantarjian, Farhad Ravandi, Padmanee Sharma, Guillermo Garcia-Manero, Naval Daver
In the past few years, our improved understanding of the pathogenesis of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) has led to remarkable advances in the development of novel therapeutic approaches for these diseases. This chapter summarizes the available clinical data with immune-based therapeutic modalities in AML and MDS, focusing on monoclonal antibodies, T cell engager antibodies, chimeric antigen receptor (CAR)-T cells, and checkpoint blockade via blockade of PD-1/PD-L1 or CTLA4. Numerous clinical trials are currently ongoing in patients with AML and MDS, both in the frontline and relapsed refractory setting...
2018: Advances in Experimental Medicine and Biology
Kazuhiro Togasaki, Yasutaka Sukawa, Takanori Kanai, Hiromasa Takaishi
Standard treatment options for patients with advanced gastric cancer (GC) offer limited efficacy and are associated with some toxicity, which necessitates the development of more effective therapies for improving the treatment outcomes for this disease. Immunotherapy involving immune checkpoint inhibitors (ICIs) which inhibit the programmed death 1 (PD-1)/programmed death ligand 1 interaction has emerged as a new treatment option. Nivolumab, a human IgG4 monoclonal antibody inhibitor of PD-1, has demonstrated promising clinical activity and induced durable responses in patients with advanced GC...
2018: OncoTargets and Therapy
Paolo Manca, Luis E Raez, Matthew Salzberg, Jorge Sanchez, Brian Hunis, Christian Rolfo
Head and neck squamous cell carcinomas (HNSCC) previously had limited treatment options once patients had progressed on systemic chemotherapy. With recent advances, immunotherapy now plays an important role in the treatment of advanced disease with improved outcomes as compared to cytotoxic chemotherapy. Areas covered: This article reviews the effects of the immune system and how it influences the development and response to HNSCC therapy. We additionally provide a summary of immunotherapy treatments available as well as their applicable clinical trials that led to their approval...
December 11, 2018: Expert Opinion on Biological Therapy
Thomas V Guy, Shiv Pillai
Genomic biomarkers will help to elucidate which cancer patients will benefit from PD-1 blockade immunotherapy.
December 7, 2018: Science Immunology
Hayley Leeman, Elwira Kaminska, Deborah Green, Mark Bodman-Smith, Andrew Gravett, Katherine Bodman-Smith, John Copier, Gary Coulton, Alberto Fusi, Angus G Dalgleish
BACKGROUND: Despite the majority of patients do not gain any benefit from dendritic cells (DC) vaccines, this approach has occasionally given rise to dramatic responses in melanoma. Biomarkers are crucial to identify which patients are more likely to respond. We looked for correlations between pre- or post- vaccination biomarkers and clinical outcomes to DC therapy in a cohort of patients with stage IV melanoma receiving a vaccine with autologous ex-vivo expanded DCs pulsed with allogeneic tumor cell lysate...
December 7, 2018: Translational Oncology
Jose Batista da Costa, Ewan A Gibb, Timo K Nykopp, Miles Mannas, Alexander W Wyatt, Peter C Black
BACKGROUND: Despite years of slow progress, muscle invasive bladder cancer (MIBC) is finally entering the era of molecularly guided targeted therapy. However, tumor heterogeneity is high in MIBC and may impact treatment response and resistance. The objective of this review is to dissect recent insights into inter- and intratumor heterogeneity (ITH) in MIBC, with emphasis on the clinical implications of this heterogeneity for biomarker-driven strategies and the development of new therapies...
December 8, 2018: Urologic Oncology
Aziz Zaanan, Julien Taieb
The MSI phenotype in colon cancer is a good prognostic factor, with an impact probably more pronounced for stage II than stage III tumor. This survival advantage may be related to the tumor-infiltrating lymphocytes observed in MSI tumors, thus explaining the existence of a probably more effective anti-tumor immune response. In addition, the MSI status would also be a biomarker able to predict the lack of efficacy of adjuvant 5-fluorouracil (5FU) chemotherapy. In contrast, as observed in MSS colon cancer, the MSI tumors would have a survival benefit with the addition of oxaliplatin to adjuvant 5FU chemotherapy...
December 4, 2018: Bulletin du Cancer
C Longvert, P Saiag
Incidence of malignant melanoma has been increasing since the 1980s. For loco-regional stages, surgery is still the best treatment. Melanoma has a high distant metastatic potential and prognosis of advanced stages was until recently very poor. Since 2011 however, a real revolution has taken place in the treatment of metastatic melanoma. This is based upon considerably improved knowledge of the molecular mechanisms of melanoma and cancer immunology. Thus, two new classes of systemic therapeutic agents are now available: immunotherapies (immunological checkpoint inhibitors), which increase the antitumor immune response, and targeted therapies (BRAF and MEK inhibitors) for patients with BRAF V600-mutant melanoma...
December 5, 2018: La Revue de Médecine Interne
Samuel Lee, Deirdre J Cohen
Esophageal cancer is a heterogeneous cancer comprised of differing cells of origin, molecular changes, and immune microenvironments. To date, most advances have been made in chemotherapy regimens where a one-size-fits-all approach is used. As a result, there remains a lack of tailored treatment options for such a heterogeneous cancer. This paper highlights the current standard of care treatment options as well as active areas of clinical research. Areas covered: The authors review the key trials that have led to current standard of care treatment including pivotal chemotherapy and targeted therapy trials...
December 7, 2018: Expert Opinion on Pharmacotherapy
Jin-Huan Cui, Kai-Rong Lin, Song-Hua Yuan, Ya-Bin Jin, Xiang-Ping Chen, Xi-Kang Su, Jun Jiang, Ying-Ming Pan, Shao-Long Mao, Xiao-Fan Mao, Wei Luo
There is increasing evidence that deep sequencing-based T cell repertoire can sever as a biomarker of immune response in cancer patients; however, the characteristics of T cell repertoire including diversity and similarity, as well as its prognostic significance in patients with cervical cancer (CC) remain unknown. In this study, we applied a high throughput T cell receptor (TCR) sequencing method to characterize the T cell repertoires of peripheral blood samples from 25 CC patients, 30 cervical intraepithelial neoplasia (CIN) patients and 20 healthy women for understanding the immune alterations during the cervix carcinogenesis...
2018: Frontiers in Immunology
Taylor J Jensen, Aaron M Goodman, Shumei Kato, Christopher K Ellison, Gregory A Daniels, Lisa Kim, Prachi Nakashe, Erin McCarthy, Amin R Mazloom, Graham McLennan, Daniel S Grosu, Mathias Ehrich, Razelle Kurzrock
Inhibitors of the PD-1/PD-L1/CTLA4 immune checkpoint pathway have revolutionized cancer treatment. Indeed, some patients with advanced, refractory malignancies achieve durable responses; however, only a subset of patients benefit, necessitating new biomarkers to predict outcome. Interrogating cell-free DNA (cfDNA) isolated from plasma (liquid biopsy) provides a promising method for monitoring response. We describe the use of low-coverage, genome-wide sequencing of cfDNA, validated extensively for non-invasive prenatal testing (NIPT), to detect tumor-specific copy number alterations, and the development of a new metric--the genome instability number (GIN)--to monitor response to these drugs...
December 6, 2018: Molecular Cancer Therapeutics
Baoan Hong, Lin Cai, Jiangyi Wang, Shengjie Liu, Jingcheng Zhou, Kaifang Ma, Jiufeng Zhang, Bowen Zhou, Xiang Peng, Ning Zhang, Kan Gong
BACKGROUND: Programmed death ligand-1 (PD-L1) is a potential predictive biomarker for immunotherapy in several malignancies. However, the expression level and clinical significance of PD-L1 in von Hippel-Lindau (VHL)-associated hereditary clear-cell renal cell carcinoma (ccRCC) remain unclear. PATIENTS AND METHODS: Surgical specimens were recruited from 129 patients with sporadic ccRCC and 26 patients with VHL-associated hereditary ccRCC. The PD-L1 expression level was assessed using immunohistochemistry...
November 13, 2018: Clinical Genitourinary Cancer
Lisa H Butterfield, Mary L Disis, Bernard A Fox, David R Kaufman, Samir N Khleif, Ena Wang
Identification of biomarkers in cancer immunotherapy that predict therapeutic response and/or limit adverse events are a critical need in the field. To address recent progress and hurdles around cancer biomarker development and utilization, the Society for Immunotherapy of Cancer (SITC) convened a workshop, "Immuno-Oncology Biomarkers: State of the Art," on May 16-17, 2018. Topics discussed included challenges in handling biospecimens, identification and validation of new biomarkers, data sharing, and collaborating across disciplines to advance biomarker development...
December 4, 2018: Journal for Immunotherapy of Cancer
Johann Steiner, Harald Prüss, Stephan Köhler, Thomas Frodl, Alkomiet Hasan, Peter Falkai
OBJECTIVES: Despite intensive research, schizophrenia and schizoaffective disorders continue to be theoretical constructs that describe clinical syndromes and no pathophysiologically defined diseases. Moreover, there are no clear biomarkers at hand. Therefore, these diagnoses are still set up based on clinical ICD-10 / DSM-5 criteria and the exclusion of alcohol- / drug-associated, systemic or other brain organic causes. METHODS: Recently, autoimmune encephalitis with psychotic symptoms caused by specific antineuronal antibodies has been identified as rare, but potentially treatable differential diagnosis...
December 4, 2018: World Journal of Biological Psychiatry
Mayassa J Bou-Dargham, Yuhang Liu, Qing-Xiang Amy Sang, Jinfeng Zhang
In the era of immunotherapy and personalized medicine, there is an urgent need for advancing the knowledge of immune evasion in different cancer types and identifying reliable biomarkers that guide both therapy selection and patient inclusion in clinical trials. Given the differential immune responses and evasion mechanisms in breast cancer, we expect to identify different breast cancer groups based on their expression of immune-related genes. For that, we used the sequential biclustering method on The Cancer Genome Atlas RNA-seq breast cancer data and identified 7 clusters...
2018: PloS One
Taku Fujimura, Yota Sato, Kayo Tanita, Yumi Kambayashi, Atsushi Otsuka, Yasuhiro Fujisawa, Koji Yoshino, Shigeto Matsushita, Takeru Funakoshi, Hiroo Hata, Yuki Yamamoto, Hiroshi Uchi, Yumi Nonomura, Ryota Tanaka, Megumi Aoki, Keisuke Imafuku, Hisako Okuhira, Naoko Wada, Hiroyuki Irie, Takanori Hidaka, Akira Hashimoto, Setsuya Aiba
Antibodies against programmed cell death protein 1, such as nivolumab and pembrolizumab, are widely used for treating various cancers, including advanced melanoma. Nivolumab significantly prolongs survival in patients with metastatic melanoma, and sequential administration with lipilimumab may improve outcomes when switched at the appropriate time. Biomarkers are therefore needed to evaluate nivolumab efficacy soon after first administration. This study analyzed serum levels of soluble cluster of differentiation 163 (sCD163) in 59 cases of advanced cutaneous melanoma and 16 cases of advanced mucosal melanoma treated using nivolumab...
2018: Frontiers in Oncology
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