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lung cancer immunology

S Kanda, K Goto, H Shiraishi, E Kubo, A Tanaka, H Utsumi, K Sunami, S Kitazono, H Mizugaki, H Horinouchi, Y Fujiwara, H Nokihara, N Yamamoto, H Hozumi, T Tamura
BACKGROUND: The human IgG4 monoclonal antibody nivolumab targets programmed cell death-1 (PD-1) and promotes antitumor response by blocking the interaction of PD-1 with its ligands. This single-center phase Ib study investigated the tolerability, safety, and pharmacokinetics of nivolumab combined with standard chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients who had stage IIIB without indication for definitive radiotherapy, stage IV, or recurrent NSCLC were eligible...
October 20, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
E C Martino, G Misso, P Pastina, S Costantini, F Vanni, C Gandolfo, C Botta, F Capone, A Lombardi, L Pirtoli, P Tassone, C Ulivieri, P Tagliaferri, M G Cusi, M Caraglia, P Correale
The mPEBev is an anticancer regimen which combines a chemotherapy doublet, based on cisplatin and oral etoposide (mPE), with bevacizumab (mPEBev), a mAb targeting the vasculo-endothelial growth factor (VEGF). In previous studies, this regimen showed powerful anti-angiogenetic effects and significant antitumor activity in metastatic non-small-cell lung cancer (mNSCLC) patients. We also recorded the best benefit in patients exhibiting low-systemic inflammatory profile at baseline. On these bases, we hypothesized that mPEBev antitumor activity could be partially related to bevacizumab-associated immunological effects...
2016: Cell Death Discovery
Gregory P Kalemkerian
Small cell lung cancer (SCLC) is a high-grade neuroendocrine tumor characterized by rapid growth, early metastatic spread, and initial responsiveness to therapy. Although the incidence of SCLC is declining, it remains one of the common causes of cancer-related mortality. Initial evaluation of patients with SCLC should focus on determining the extent of disease and the ability of the patient to tolerate specific therapy. Positron emission tomography (PET) can improve the accuracy of staging and treatment planning in many patients...
October 2016: Seminars in Respiratory and Critical Care Medicine
Jonas Steenbrugge, Koen Breyne, Sofie Denies, Melissa Dekimpe, Kristel Demeyere, Olivier De Wever, Peter Vermeulen, Steven Van Laere, Niek N Sanders, Evelyne Meyer
Breast tumorigenesis is classically studied in mice by inoculating tumor cells in the fat pad, the adipose compartment of the mammary gland. Alternatively, the mammary ducts, which constitute the luminal mammary gland compartment, also provide a suitable inoculation site to induce breast cancer in murine models. The microenvironments in these compartments influence tumor cell progression, yet this effect has not been investigated in an immunocompetent context. Here, we compared both mammary gland compartments as distinct inoculation sites, taking into account the immunological aspect by inoculating 4T1 tumor cells in immunocompetent mice...
October 6, 2016: Journal of Mammary Gland Biology and Neoplasia
Patrick H Lizotte, Elena V Ivanova, Mark M Awad, Robert E Jones, Lauren Keogh, Hongye Liu, Ruben Dries, Christina Almonte, Grit S Herter-Sprie, Abigail Santos, Nora B Feeney, Cloud P Paweletz, Meghana M Kulkarni, Adam J Bass, Anil K Rustgi, Guo-Cheng Yuan, Donald W Kufe, Pasi A Jänne, Peter S Hammerman, Lynette M Sholl, F Stephen Hodi, William G Richards, Raphael Bueno, Jessie M English, Mark A Bittinger, Kwok-Kin Wong
BACKGROUND. Immune checkpoint blockade improves survival in a subset of patients with non-small-cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. METHODS. We performed comprehensive flow cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next-generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC)...
September 8, 2016: JCI Insight
Jung Hoon Kim, Bum Jun Kim, Hyeong Su Kim, Jung Han Kim
Cancer immunotherapy is at dawn of the Renaissance after the Medieval Dark Ages. Recent advances of understanding tumor immunology and molecular drug development are leading us to the epoch of cancer immunotherapy. Some types of immunotherapy have shown to provide survival benefit for patients with solid tumors such as malignant melanoma, renal cell carcinoma, or non-small cell lung cancer. Several studies have suggested that immune checkpoint inhibition might be effective in some patients with gastrointestinal cancers...
2016: Journal of Cancer
María Del Mar Valenzuela-Membrives, Francisco Perea-García, Abel Sanchez-Palencia, Francisco Ruiz-Cabello, Mercedes Gómez-Morales, María Teresa Miranda-León, Inmaculada Galindo-Angel, María Esther Fárez-Vidal
Immune cell infiltration is a common feature of many human solid tumors. Innate and adaptative immune systems contribute to tumor immunosurveillance. We investigated whether tumors evade immune surveillance by inducing states of tolerance and/or through the inability of some immune subpopulations to effectively penetrate tumor nests. Immunohistochemistry and flow cytometry analysis were used to study the composition and distribution of immune subpopulations in samples of peripheral blood, tumor tissue (TT), adjacent tumor tissue (ATT), distant non-tumor tissue (DNTT), cancer nests, cancer stroma, and invasive margin in 61 non-small-cell lung cancer (NSCLC) patients...
September 26, 2016: Oncotarget
Mohanad Aldarouish, Cailian Wang
Among several types of tumor, lung cancer is considered one of the most fatal and still the main cause of cancer-related deaths. Although chemotherapeutic agents can improve survival and quality of life compared with symptomatic treatment, cancers usually still progress after chemotherapy and are often aggravated by serious side effects. In the last few years there has been a growing interest in immunotherapy for lung cancer based on promising preliminary results in achieving meaningful and durable treatments responses with minimal manageable toxicity...
September 29, 2016: Journal of Experimental & Clinical Cancer Research: CR
Kaname Ohyama, Haruka Yoshimi, Nozomi Aibara, Yoichi Nakamura, Yasuyoshi Miyata, Hideki Sakai, Fumihiko Fujita, Yoshitaka Imaizumi, Anil K Chauhan, Naoya Kishikawa, Naotaka Kuroda
Cancer immunotherapies such as antibodies targeting T cell checkpoints, or adaptive tumor-infiltrating lymphocyte (TIL) transfer, have been developed to boost the endogenous immune response against human malignancies. However, activation of T cells by such antibodies can lead to the risk of autoimmune diseases. Also, the selection of tumor-reactive T cells for TIL relies on information regarding mutated antigens in tumors and does not reflect other factors involved in protein antigenicity. It is therefore essential to engineer therapeutic interventions by which T cell reactivity against tumor cells is selectively enhanced (i...
September 29, 2016: International Journal of Cancer. Journal International du Cancer
Cesare Gridelli, Paolo A Ascierto, Massimo C P Barberis, Enriqueta Felip, Edward B Garon, Mary O'brien, Suresh Senan, Francesca Casaluce, Assunta Sgambato, Vali Papadimitrakopoulou, Filippo De Marinis
INTRODUCTION: The potential long term survival gain, related to immune adaptability and memory, the potential activity across multiple tumour types through targeting the immune system, and the opportunity for combinations offered by the unique mechanism of actions and safety profile of these new agents, all support the role of immunotherapy in the cancer treatment pathway or paradigm. AREAS COVERED: The authors discuss the recent advances in the understanding of immunology and antitumor immune responses that have led to the development of new immunotherapies, including monoclonal antibodies that inhibit immune checkpoint pathways, such as Programmed Death-1 (PD-1) and Cytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA-4)...
September 21, 2016: Expert Opinion on Biological Therapy
Severin Schmid, Uyen-Thao LE, Benedikt Haager, Olga Mayer, Irene Dietrich, Mirjam Elze, Lars Johann Kemna, Gernot Zissel, Bernward Passlick
BACKGROUND: The tumor microenvironment plays a critical role in tumor growth and spreading. Tumor-associated macrophages (TAM) make up a large proportion of the tumor mass and are one of the main producers of CC-chemokine ligand 18 (CCL18), which is believed to carry out important functions in the immunological interactions that promote tumor progression. MATERIALS AND METHODS: Cytokines/chemokines were measured in bronchoalveolar lavage (BAL) from the tumor site and serum before and after resection in patients with proven non-small cell lung cancer (NSCLC)...
September 2016: Anticancer Research
Ulrich T Egle, Matthias Franz, Peter Joraschky, Astrid Lampe, Inge Seiffge-Krenke, Manfred Cierpka
In the last decade strong empirical evidence from several long-term studies supports the conclusion that physical and sexual abuse as well as emotional deprivation in childhood make people significantly more vulnerable to mental and functional disorders across their lifetime. Additionally, an increased vulnerability to several somatic disorders (cardiovascular disorders, type-2-diabetes, hepatitis, chronic obstructive pulmonary disease (COPD), immunological and pain disorders, pharynx and lung cancer) was demonstrated - most of them with a reduced life expectancy...
October 2016: Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz
Yasuto Akiyama, Chizu Nonomura, Ryota Kondou, Haruo Miyata, Tadashi Ashizawa, Chie Maeda, Koichi Mitsuya, Nakamasa Hayashi, Yoko Nakasu, Ken Yamaguchi
Immune checkpoint antibody-mediated blockade has gained attention as a new cancer immunotherapy strategy. Accumulating evidence suggests that this therapy imparts a survival benefit to metastatic melanoma and non-small cell lung cancer patients. A substantial amount of data on immune checkpoint antibodies has been collected from clinical trials; however, the direct effect of the antibodies on human peripheral blood mononuclear cells (PBMCs) has not been exclusively investigated. In this study, we developed an anti-programmed death-1 (PD-1) antibody (with biosimilarity to nivolumab) and examined the effects of the antibody on PBMCs derived from cancer patients...
September 2016: International Journal of Oncology
Huiying Liu, Rong Xing, Xuefang Cheng, Qingran Li, Fang Liu, Hui Ye, Min Zhao, Hong Wang, Guangji Wang, Haiping Hao
Tryptophan metabolism is essential in diverse kinds of tumors via regulating tumor immunology. However, the direct role of tryptophan metabolism and its signaling pathway in cancer cells remain largely elusive. Here, we establish a mechanistic link from L-type amino acid transporter 1 (LAT1) mediated transport of tryptophan and the subsequent de-novo NAD+ synthesis to SIRT1-FOXO1 regulated apoptotic signaling in A549 cells in response to NQO1 activation. In response to NQO1 activation, SIRT1 is repressed leading to the increased cellular accumulation of acetylated FOXO1 that transcriptionally activates apoptotic signaling...
August 23, 2016: Oncotarget
Rafael Rosell, Elia Neninger, Marianne Nicolson, Rudolf M Huber, Sumitra Thongprasert, Purvish M Parikh, Erik D'Hondt
Abnormalities in the Epidermal Growth Factor (EGF) and EGF receptor pathway promote progression of non-small cell lung cancer (NSCLC). Immunisation with EGF vaccine induces specific, neutralizing anti-EGF antibodies that prevent binding of the ligand to its receptor. This concept of Pathway Targeted Immunotherapy (PTI) was validated in vitro by dose-related suppression of EGFR, Akt and Erk 1-2 phosphorylation in cell lines with different mutations. A randomised phase II trial demonstrated improved overall survival (OS) in advanced NSCLC subgroups showing clear immunological response...
August 23, 2016: Journal of Thoracic Oncology
David Clever, Rahul Roychoudhuri, Michael G Constantinides, Michael H Askenase, Madhusudhanan Sukumar, Christopher A Klebanoff, Robert L Eil, Heather D Hickman, Zhiya Yu, Jenny H Pan, Douglas C Palmer, Anthony T Phan, John Goulding, Luca Gattinoni, Ananda W Goldrath, Yasmine Belkaid, Nicholas P Restifo
Cancer cells must evade immune responses at distant sites to establish metastases. The lung is a frequent site for metastasis. We hypothesized that lung-specific immunoregulatory mechanisms create an immunologically permissive environment for tumor colonization. We found that T-cell-intrinsic expression of the oxygen-sensing prolyl-hydroxylase (PHD) proteins is required to maintain local tolerance against innocuous antigens in the lung but powerfully licenses colonization by circulating tumor cells. PHD proteins limit pulmonary type helper (Th)-1 responses, promote CD4(+)-regulatory T (Treg) cell induction, and restrain CD8(+) T cell effector function...
August 25, 2016: Cell
Vincent Sibaud, Nicole R Lebœuf, Henri Roche, Viswanath R Belum, Laurence Gladieff, Marion Deslandres, Marion Montastruc, Audrey Eche, Emmanuelle Vigarios, Florence Dalenc, Mario E Lacouture
Taxanes (docetaxel and paclitaxel) are among the most commonly prescribed anticancer drugs approved for the treatment of metastatic or locally advanced breast, non-small cell lung, prostate, gastric, head and neck, and ovarian cancers, as well as in the adjuvant setting for operable node-positive breast cancers. Although the true incidence of dermatological adverse events (AEs) in patients receiving taxanes is not known, and has never been prospectively analysed, they clearly represent one of the major AEs associated with these agents...
August 22, 2016: European Journal of Dermatology: EJD
Andrew Paul Demidowich, Amartya Kundu, James C Reynolds, Francesco S Celi
A 42-year-old female with immunoglobulin A deficiency and recurrent sinopulmonary infections underwent thyroidectomy for papillary thyroid cancer (PTC). Follow-up (123)I scintigraphy demonstrated diffuse pulmonary uptake, suggesting metastatic disease. However, subsequent pathologic, biochemical and radiographic testing proved that she was in fact disease free, and the initial (123)I pulmonary uptake was identified as a false positive. Inflammatory conditions may rarely cause iodine uptake in non-thyroidal tissues due to local retention, organification, and/or immunologic utilization...
September 2016: Nuclear Medicine and Molecular Imaging
Susan F Slovin
PURPOSE OF REVIEW: The purpose of this review is to identify possible reasons why prostate cancer suboptimally responds to immune therapies. RECENT FINDINGS: Interrogation of the intraprostatic milieu suggests that within the normal prostate, foci of tumor can be surrounded by inflammatory cells that may or may not represent foci of immune sensitivity. Whether or not these cells are specific 'immune responders' depends on a multiplicity of factors within the host and intratumoral/stromal milieu...
November 2016: Current Opinion in Urology
Claud Grigg, Naiyer A Rizvi
Research in cancer immunology is currently accelerating following a series of cancer immunotherapy breakthroughs during the last 5 years. Various monoclonal antibodies which block the interaction between checkpoint molecules PD-1 on immune cells and PD-L1 on cancer cells have been used to successfully treat non-small cell lung cancer (NSCLC), including some durable responses lasting years. Two drugs, nivolumab and pembrolizumab, are now FDA approved for use in certain patients who have failed or progressed on platinum-based or targeted therapies while agents targeting PD-L1, atezolizumab and durvalumab, are approaching the final stages of clinical testing...
2016: Journal for Immunotherapy of Cancer
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