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Clinical immunology and lung cancer

Biagio Ricciuti, Carlo Genova, Andrea De Giglio, Maria Bassanelli, Maria Giovanna Dal Bello, Giulio Metro, Marta Brambilla, Sara Baglivo, Francesco Grossi, Rita Chiari
PURPOSE: Immune-checkpoint inhibitors (ICIs) represent the standard of care for platinum-pretreated advanced non-small cell lung cancer patients. Patients treated with ICIs may experience immune-related adverse events (irAEs), that might reflect antitumor responses. Here we evaluated nivolumab efficacy according to the development of irAEs. METHODS: We conducted a multicenter retrospective study of patients with advanced NSCLC treated with nivolumab between October 2013 and September 2017...
December 1, 2018: Journal of Cancer Research and Clinical Oncology
Mei-Chun Cai, Minjiang Chen, Pengfei Ma, Jie Wu, Haijiao Lu, Shengzhe Zhang, Jin Liu, Xiaojing Zhao, Guanglei Zhuang, Zhuang Yu, Yujie Fu
Somatic KEAP1-NRF2 pathway alterations are frequently detected in both lung adenocarcinomas and squamous cell carcinomas. However, the biological characteristics and molecular subtypes of KEAP1/NRF2-mutant lung cancer remain largely undefined. Here, we performed a stepwise, integrative analytic and experimental interrogation of primary tumors and cancer cell lines harboring KEAP1 or NFE2L2 (encoding NRF2) gene mutations. First, we discovered that KEAP1/NRF2-mutant lung cancer presented APOBEC-mediated mutational signatures, impaired tumor angiogenesis, elevated hypoxic stress and deficient immune-cell infiltrates...
November 8, 2018: International Journal of Cancer. Journal International du Cancer
Suneel D Kamath, Priya U Kumthekar
While the CNS has long been viewed as an immune-privileged environment, a paradigm shift in neuro-immunology has elevated the role of systemic immunotherapy for the treatment of metastatic disease. Increasing knowledge regarding the presence of a CNS lymphatic system and the physical and biochemical alteration of the blood brain barrier (BBB) by the tumor microenvironment suggests immune cell trafficking in and out of the CNS is possible. Emerging clinical data suggest immune checkpoint inhibitors (ICIs) can stimulate T cells peripherally to in turn have anti-tumor effects in the CNS...
2018: Frontiers in Oncology
Luis Aj Mur, Sharon A Huws, Simon Js Cameron, Paul D Lewis, Keir E Lewis
The lung microbiome has been shown to reflect a range of pulmonary diseases-for example: asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. Studies have now begun to show microbiological changes in the lung that correlate with lung cancer (LC) which could provide new insights into lung carcinogenesis and new biomarkers for disease screening. Clinical studies have suggested that infections with tuberculosis or pneumonia increased the risk of LC possibly through inflammatory or immunological changes...
2018: Ecancermedicalscience
Francesco Facchinetti, Paola Bordi, Alessandro Leonetti, Sebastiano Buti, Marcello Tiseo
Programed cell death-1/programed death ligand-1 (PD-1/PD-L1) blockade represents an affirmed reality in the treatment of advanced non-small-cell lung cancer (NSCLC) patients. Atezolizumab, an anti-PD-L1 agent, figures among the drugs that provide previously unenvisaged outcomes in the pretreated setting of metastatic NSCLC. Increasing evidence vouches for the early administration of PD-1/PD-L1 blockers in untreated patients, encompassing atezolizumab combinations with chemotherapy and the anti-angiogenic agent bevacizumab...
2018: Drug Design, Development and Therapy
Di Huang, Jianing Chen, Linbin Yang, Qian Ouyang, Jiaqian Li, Liyan Lao, Jinghua Zhao, Jiang Liu, Yiwen Lu, Yue Xing, Fei Chen, Fengxi Su, Herui Yao, Qiang Liu, Shicheng Su, Erwei Song
Activation-induced cell death (AICD) of T lymphocytes can be exploited by cancers to escape immunological destruction. We demonstrated that tumor-specific cytotoxic T lymphocytes (CTLs) and type 1 helper T (TH 1) cells, rather than type 2 helper T cells and regulatory T cells, were sensitive to AICD in breast and lung cancer microenvironments. NKILA, an NF-κB-interacting long noncoding RNA (lncRNA), regulates T cell sensitivity to AICD by inhibiting NF-κB activity. Mechanistically, calcium influx in stimulated T cells via T cell-receptor signaling activates calmodulin, thereby removing deacetylase from the NKILA promoter and enhancing STAT1-mediated transcription...
October 2018: Nature Immunology
Steven Lehrer, Peter H Rheinstein
BACKGROUND: One aspect of smoking and lung cancer that has not been closely examined, is that regarding genes that may predispose to tobacco dependence. Smoking and mental illness are tightly linked, apparently the result of smokers using cigarettes to self-medicate for mental problems. The gene for solute carrier family 18 member A1 (vesicular monoamine transporter; SLC18A1) is of particular interest in this regard because of its association with schizophrenia, autism and bipolar illness as well as with cancer...
September 2018: Cancer Genomics & Proteomics
Fathia Mami-Chouaib, Charlotte Blanc, Stéphanie Corgnac, Sophie Hans, Ines Malenica, Clémence Granier, Isabelle Tihy, Eric Tartour
CD8+ T lymphocytes are the major anti-tumor effector cells. Most cancer immunotherapeutic approaches seek to amplify cytotoxic T lymphocytes (CTL) specific to malignant cells. A recently identified subpopulation of memory CD8+ T cells, named tissue-resident memory T (TRM ) cells, persists in peripheral tissues and does not recirculate. This T-cell subset is considered an independent memory T-cell lineage with a specific profile of transcription factors, including Runx3+ , Notch+ , Hobit+ , Blimp1+ , BATF+ , AHR+ , EOMESneg and Tbetlow ...
September 4, 2018: Journal for Immunotherapy of Cancer
Yushu Zhou, Baiming Zhao, Wanyin Wu, Xiaobing Yang, Shunqin Long, Hong Deng, Wenfeng He, Guiya Liao, Qiuping Li, Zhen Xie
BACKGROUND: Cancer-related fatigue (CRF) is the most common symptom in patients with advanced non-small cell lung cancer (NSCLC) undergoing treatment with chemotherapy. However, evidence upon which to base management strategies is scarce. Traditional Chinese Medicine (TCM) has been shown to be beneficial to patients with CRF. Chinese herbal injections should be administered under an evidence-based approach. This trial aims to assess the efficacy and safety of the addition of the Shenmai injection (SMI) to conventional therapy for CRF in NSCLC patients undergoing chemotherapy...
September 4, 2018: Trials
Alok Mishra, Mukesh Verma
Utilizing biology of PD-1: PD-L1 interaction related pathways for cancer immunotherapy is an emerging concept in cancer research. However, there is limited literature on epigenetic regulation of PD1 gene (PDCD1). Promising data from clinical trials of PD/PDl-1 immunotherapy in melanoma, renal cancers, colorectal and lung cancers has generated a lot of hope for successful treatment of patients. Immunotherapy in cancers has a significant role in strategizing NCI's Cancer Moonshot Program of US NIH and FDA policies...
2018: Methods in Molecular Biology
Simona Ferro, Veronica Huber, Licia Rivoltini
If immunotherapy is currently considered as a valid treatment strategy in oncology, the concept that cancer could be cured by the mere manipulation of the immune system was almost inconceivable until few years ago, particularly in lung cancer. The use of immune checkpoint inhibitors has instead demonstrated to mediate significant long-term disease control so to rapidly enter clinical practice and represent the basis for most of the combination approaches under development. In light of the revolutionary results achieved through the pivotal clinical trials and the large expectations about the possibility to further improve clinical benefit and discover novel therapeutic targets, it is becoming nowadays mandatory to increase our knowledge on the basics of immunology in lung cancer...
July 2018: Journal of Thoracic Disease
Rachel Bender Ignacio, Lilie L Lin, Lakshmi Rajdev, Elizabeth Chiao
This review highlights current interventional clinical trials for HIV-associated malignancies (HIVAMs), with emphasis on 4 mechanistic areas: immunomodulatory therapies and gene therapies, including immune checkpoint inhibitors; cytotoxic therapies; novel tumor-targeted and virally targeted therapies in both AIDS-defining and non-AIDS-defining cancers (NADC); and other screening or topical/ablative interventions. A search on located 35 trials, including 12 immunomodulatory or gene therapy trials, 6 cytotoxic therapy trials, 10 trials of therapies with tumor or viral molecular targets, and 7 trials evaluating screening interventions or topical or ablative therapies...
August 2018: Journal of the National Comprehensive Cancer Network: JNCCN
Weijing Cai, Dapeng Zhou, Weibo Wu, Wen Ling Tan, Jiaqian Wang, Caicun Zhou, Yanyan Lou
BACKGROUND: Mutant peptides presented by MHC (major histocompatibility complex) Class II in cancer are important targets for cancer immunotherapy. Both animal studies and clinical trials in cancer patients showed that CD4 T cells specific to tumor-derived mutant peptides are essential for the efficacy of immune checkpoint blockade therapy by PD1 antibody. RESULTS: In this study, we analyzed the next generation sequencing data of 147 lung adenocarcinoma patients from The Cancer Genome Atlas and predicted neoantigens presented by MHC Class I and Class II molecules...
August 3, 2018: BMC Genomics
Yuan Zhuang, Sihan Li, Huihui Wang, Jingbo Pi, Yuhui Xing, Guang Li
PURPOSE: It has become increasingly clear in cancer treatment that radiotherapy can be enhanced by immunotherapy. In the present study, we evaluated a novel triple combination therapy consisting of local radiotherapy, intratumoral CpG, and systemic PD-1 blockade in lung cancer models. METHODS: The efficacy of a novel triple therapy was examined by recording tumor volume and survival time. The immunologic effects of this novel triple therapy were evaluated by the frequency and percentage of immune cells and cytokines using flow cytometry...
October 2018: Journal of Cancer Research and Clinical Oncology
Yosuke Miura, Noriaki Sunaga
The clinical application of immune checkpoint inhibitors (ICIs) has led to dramatic changes in the treatment strategy for patients with advanced non-small cell lung cancer (NSCLC). Despite the observation of improved overall survival in NSCLC patients treated with ICIs, their efficacy varies greatly among different immune and molecular profiles in tumors. Particularly, the clinical significance of ICIs for oncogene-driven NSCLC has been controversial. In this review, we provide recent clinical and preclinical data focused on the relationship between oncogenic drivers and immunological characteristics and discuss the future direction of immunotherapy in NSCLC patients harboring such genetic alterations...
July 27, 2018: Cancers
Dimitra Kerdidani, Sophia Magkouta, Panagiotis Chouvardas, Vassiliki Karavana, Konstantinos Glynos, Fani Roumelioti, Spyros Zakynthinos, Els Wauters, Wim Janssens, Diether Lambrechts, George Kollias, Maria Tsoumakidou
Chronic obstructive pulmonary disease is a chronic inflammatory disorder with an increased incidence of lung cancer. The emphysema component of chronic obstructive pulmonary disease confers the greatest proportion to lung cancer risk. Although tumors create inflammatory conditions to escape immunity, the immunological responses that control growth of nascent cancer cells in pre-established inflammatory microenvironments are unknown. In this study, we addressed this issue by implanting OVA-expressing cancer cells in the lungs of mice with cigarette smoke-induced emphysema...
September 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Lucy M De La Cruz, Brian J Czerniecki
BACKGROUND: Although immunotherapy is making rapid inroads as a major treatment method for melanoma, lung, bladder, and hereditary colon cancer, breast cancer (BC) remains one of the tumors yet to experience the cellular immunology explosion despite the fact that heavy lymphocyte responses in breast tumors improve response to therapy and can predict for long-term survival. RESULTS: Immunotherapies in the form of monoclonal antibodies such as trastuzumab and pertuzumab have had an impact on HER2-positive breast cancer (HER2+BC) treatment through antibody-dependent cellular cytotoxicity...
October 2018: Annals of Surgical Oncology
Neeraj Bhalla, Rachel Brooker, Michael Brada
Immunotherapy has become standard of care in advanced non-small cell lung cancer (NSCLC) in a number of settings. Radiotherapy remains an important and potentially curative treatment for localized and locally advanced NSCLC not amenable to surgery. While the principal cytotoxic effect of ionizing radiation is via DNA damage, the effect on tumour microenvironment, promoting dendritic cell presentation of tumour-derived antigens to T cells stimulating the host adaptive immune system to mount an immune response against tumours cells, has become of particular interest when combining immunomodulating agents with radiation...
May 2018: Journal of Thoracic Disease
Aubhishek Zaman, Trever G Bivona
In lung cancer, genomics-driven comprehensive molecular profiling has identified novel chemically and immunologically addressable vulnerabilities, resulting in an increasing application of precision medicine by targeted inactivation of tumor oncogenes and immunogenic activation of host anti-tumor surveillance as modes of treatment. However, initially profound response of these targeted therapies is followed by relapse due to therapy-resistant residual disease states. Although distinct mechanisms and frameworks for therapy resistance have been proposed, accounting for and upfront prediction of resistance trajectories has been challenging...
May 2018: Annals of Translational Medicine
Edwin R Parra, Pamela Villalobos, Carmen Behrens, Mei Jiang, Apar Pataer, Stephen G Swisher, William N William, Jiexin Zhang, Jack Lee, Tina Cascone, John V Heymach, Marie-Andrée Forget, Cara Haymaker, Chantale Bernatchez, Neda Kalhor, Annikka Weissferdt, Cesar Moran, Jianjun Zhang, Ara Vaporciyan, Don L Gibbons, Boris Sepesi, Ignacio I Wistuba
BACKGROUND: The clinical efficacy observed with inhibitors of programed cell death 1/programed cell death ligand 1 (PD-L1/PD-1) in cancer therapy has prompted studies to characterize the immune response in several tumor types, including lung cancer. However, the immunological profile of non-small cell lung carcinoma (NSCLC) treated with neoadjuvant chemotherapy (NCT) is not yet fully characterized, and it may be therapeutically important. The aim of this retrospective study was to characterize and quantify PD-L1/PD-1 expression and tumor-associated immune cells (TAICs) in surgically resected NSCLCs from patients who received NCT or did not receive NCT (non-NCT)...
June 6, 2018: Journal for Immunotherapy of Cancer
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