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Lung cancer, immunotherapy

Cristina Alguacil-Núñez, Inés Ferrer-Ortiz, Elena García-Verdú, Pilar López-Pirez, Irene Maria Llorente-Cortijo, Bruno Sainz
Lung cancer, in particular non-small cell lung carcinoma (NSCLC), is the second most common cancer in both men and women and the leading cause of cancer-related deaths worldwide. Its prognosis and diagnosis are determined by several driver mutations and diverse risk factors (e.g. smoking). While immunotherapy has proven effective in some patients, treatment of NSCLC using conventional chemotherapy is largely ineffective. The latter is believed to be due to the existence of a subpopulation of stem-like, highly tumorigenic and chemoresistant cells within the tumor population known as cancer stem cells (CSC)...
May 2018: Critical Reviews in Oncology/hematology
Si-Si Wang, Wei Liu, Dalam Ly, Hao Xu, Limei Qu, Li Zhang
Evidence indicates that lung cancer development is a complex process that involves interactions between tumor cells, stromal fibroblasts, and immune cells. Tumor-infiltrating immune cells play a significant role in the promotion or inhibition of tumor growth. As an integral component of the tumor microenvironment, tumor-infiltrating B lymphocytes (TIBs) exist in all stages of cancer and play important roles in shaping tumor development. Here, we review recent clinical and preclinical studies that outline the role of TIBs in lung cancer development, assess their prognostic significance, and explore the potential benefit of B cell-based immunotherapy for lung cancer treatment...
April 8, 2018: Cellular & Molecular Immunology
John M Wrangle, Vamsidhar Velcheti, Manish R Patel, Elizabeth Garrett-Mayer, Elizabeth G Hill, James G Ravenel, Jeffrey S Miller, Mohammad Farhad, Kate Anderton, Kathryn Lindsey, Michele Taffaro-Neskey, Carol Sherman, Samantha Suriano, Marzena Swiderska-Syn, Amy Sion, Joni Harris, Andie R Edwards, Julie A Rytlewski, Catherine M Sanders, Erik C Yusko, Mark D Robinson, Carsten Krieg, William L Redmond, Jack O Egan, Peter R Rhode, Emily K Jeng, Amy D Rock, Hing C Wong, Mark P Rubinstein
BACKGROUND: Immunotherapy with PD-1 or PD-L1 blockade fails to induce a response in about 80% of patients with unselected non-small cell lung cancer (NSCLC), and many of those who do initially respond then develop resistance to treatment. Agonists that target the shared interleukin-2 (IL-2) and IL-15Rβγ pathway have induced complete and durable responses in some cancers, but no studies have been done to assess the safety or efficacy of these agonists in combination with anti-PD-1 immunotherapy...
April 5, 2018: Lancet Oncology
Koen A Marijt, Elien M Doorduijn, Thorbald van Hall
T-cell based immunotherapies through checkpoint blockade or adoptive transfer are effective treatments for a wide range of cancers like melanomas and lung carcinomas that harbor a high mutational load. The HLA class I and class II (HLA-I and HLA-II) presented neoantigens arise from genetic mutations in the cancerous cells and are ideal non-self targets for the T cell-based treatments. Although some cancer patients responded with complete regression, many others are irresponsive to checkpoint blockade treatments, or relapse after initial success...
April 4, 2018: Molecular Immunology
Aaron Sosa, Esther Lopez Cadena, Cristina Simon Olive, Niki Karachaliou, Rafael Rosell
Immunotherapy through checkpoint inhibitors is now standard practice for a growing number of cancer types, supported by overall improvement of clinical outcomes and better tolerance. One anti-CTLA-4 antibody (ipilimumab), two anti-PD-1 antibodies (pembrolizumab and nivolumab) and three anti-PD-L1 antibodies (atezolizumab, avelumab and durvalumab) have been approved for clear benefits across diverse trials. Adverse events of an immune nature associated with these agents frequently affect the skin, colon, endocrine glands, lungs and liver...
2018: Therapeutic Advances in Medical Oncology
Girish S Shroff, Patricia M de Groot, Vassiliki A Papadimitrakopoulou, Mylene T Truong, Brett W Carter
The treatment strategy in advanced non-small cell lung cancer (NSCLC) has evolved from empirical chemotherapy to a personalized approach based on histology and molecular markers of primary tumors. Targeted therapies are directed at the products of oncogenic driver mutations. Immunotherapy facilitates the recognition of cancer as foreign by the host immune system, stimulates the immune system, and alleviates the inhibition that allows the growth and spread of cancer cells. The authors describes the role of targeted therapy and immunotherapy in the treatment of NSCLC, patterns of disease present on imaging studies, and immune-related adverse events encountered with immunotherapy...
May 2018: Radiologic Clinics of North America
Jie Lan, Rui Li, Li-Mei Yin, Lei Deng, Jun Gui, Bao-Qing Chen, Lin Zhou, Mao-Bin Meng, Qiao-Rong Huang, Xian-Ming Mo, Yu-Quan Wei, Bo Lu, Adam Dicker, Jian-Xin Xue, You Lu
PURPOSE: Ablative hypofractionated radiation therapy (AHFRT) presents a therapeutic advantage compared with conventional fractionated radiation therapy (CFRT) for primary and oligometastatic cancers. However, the underlying mechanisms remain largely unknown. In the present study, we compared the immune alterations in response to AHFRT versus CFRT and examined the significance of immune regulations contributing to the efficacy of AHFRT. METHODS AND MATERIALS: We established subcutaneous tumors using syngeneic lung cancer and melanoma cells in both immunocompetent and immunocompromised mice and treated them with AHFRT and CFRT under the same biologically equivalent dose...
May 1, 2018: International Journal of Radiation Oncology, Biology, Physics
Imerio Capone, Paolo Marchetti, Paolo Antonio Ascierto, Walter Malorni, Lucia Gabriele
Nowadays, several types of tumors can benefit from the new frontier of immunotherapy, due to the recent increasing knowledge of the role of the immune system in cancer control. Among the new therapeutic strategies, there is the immune checkpoint blockade (ICB), able to restore an efficacious antitumor immunity and significantly prolong the overall survival (OS) of patients with advanced tumors such as melanoma and non-small cell lung cancer (NSCLC). Despite the impressive efficacy of these agents in some patients, treatment failure and resistance are frequently observed...
2018: Frontiers in Immunology
Anamarija Markota, Stefan Endres, Sebastian Kobold
Interleukin-22 (IL-22) is a member of IL-10 family of cytokines. IL-22 induces proliferative and anti-apoptotic signaling pathways and production of anti-microbial molecules that enhance tissue regeneration and host defense. IL-22 has also been identified as a cancer-promoting cytokine since deregulation of the IL-22-IL-22R1 system is linked to different cancer entities including lung, breast, gastric, pancreatic and colon cancers. T cells and innate lymphoid cells are the main cellular sources of IL-22. Expression of its specific receptor IL-22R1 is restricted to the non-hematopoietic cells which makes the IL-22-IL-22R1 pathway an attractive target for anti-cancer therapy...
April 4, 2018: Human Vaccines & Immunotherapeutics
Ozge Nur Aktaş, Ayşe Bilge Öztürk, Baran Erman, Suat Erus, Serhan Tanju, Şükrü Dilege
PURPOSE: One of the key immune cells involved in the pathogenesis of lung cancer is natural killer (NK) cells and these cells are novel targets for therapeutic applications in lung cancer. The purpose of this review is to summarize the current literature on lung cancer pathogenesis with a focus on the interaction between NK cells and smoking, how these factors are related to the pathogenesis of lung cancer and how NK cell-based immunotherapy effect lung cancer survival. METHODS: The relevant literature from PubMed and Medline databases is reviewed in this article...
April 3, 2018: Journal of Cancer Research and Clinical Oncology
Rebecca Voelker
No abstract text is available yet for this article.
April 3, 2018: JAMA: the Journal of the American Medical Association
Jonathan S Kurman, Septimiu D Murgu
Immunotherapy agents in metastatic non-small cell lung cancer (NSCLC) can result in improved quality of life and survival when compared with platinum-based chemotherapy. Novel response patterns such as pseudoprogression and hyperprogression, however, have been described and pose a challenge to treating physicians. Predictors of hyperprogressive disease (HPD) have not yet been identified. Evaluation and management by a multidisciplinary team involving medical and radiation oncologists, thoracic radiologists, and proceduralists is necessary to identify this subset of patients in a timely manner...
February 2018: Journal of Thoracic Disease
Chen Pang, Limei Yin, Xiaojuan Zhou, Chuanfen Lei, Ruizhan Tong, Meijuan Huang, Youling Gong, Zhenyu Ding, Jianxin Xue, Jiang Zhu, Yongsheng Wang, Li Ren, Lin Zhou, Jin Wang, Feng Peng, Qiao Zhou, You Lu
Background: Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have been identified as novel targets for immunotherapy, with PD-L1 as a potential predictive biomarker. However, a specific antibody for PD-L1 expression is an immediate requirement. Meanwhile, the clinicopathological identification of patients with positive PD-L1 remains unclear. Methods: The present study adopted three anti-PD-L1 IHC antibodies, SP142, SP263, and UMAB228 to test PD-L1 expression in 84 non-small cell lung cancer (NSCLC) specimens...
February 2018: Journal of Thoracic Disease
Robert A Wolff, Andrea Wang-Gillam, Hector Alvarez, Hervé Tiriac, Dannielle Engle, Shurong Hou, Abigail F Groff, Anthony San Lucas, Vincent Bernard, Kelvin Allenson, Jonathan Castillo, Dong Kim, Feven Mulu, Jonathan Huang, Bret Stephens, Ignacio I Wistuba, Matthew Katz, Gauri Varadhachary, YoungKyu Park, James Hicks, Arul Chinnaiyan, Louis Scampavia, Timothy Spicer, Chiara Gerhardinger, Anirban Maitra, David Tuveson, John Rinn, Gregory Lizee, Cassian Yee, Arnold J Levine
This manuscript follows a single patient with pancreatic adenocarcinoma for a five year period, detailing the clinical record, pathology, the dynamic evolution of molecular and cellular alterations as well as the responses to treatments with chemotherapies, targeted therapies and immunotherapies. DNA and RNA samples from biopsies and blood identified a dynamic set of changes in allelic imbalances and copy number variations in response to therapies. Organoid cultures established from biopsies over time were employed for extensive drug testing to determine if this approach was feasible for treatments...
March 13, 2018: Oncotarget
Naghmehossadat Eshghi, Linda Garland, Emily Saghar Nia, Robert Betancourt, Elizabeth Krupinski, Phillip H Kuo
Objective: For patients undergoing immunotherapy with nivolumab for lung cancer, determine if increased18 F-FDG uptake in the thyroid gland predicts development of thyroiditis with subsequent hypothyroidism. Secondarily, determine if18 F-FDG uptake in the thyroid gland correlates with administered cycles of nivolumab. Materials and Methods: Retrospective chart review over 2 years found 18 lung cancer patients treated with nivolumab and with18 F-FDG PET/CT scans pre- and during therapy. Standardized uptake value (SUV) mean and maximum and total lesion glycolysis (TLG) of the thyroid gland were measured...
March 29, 2018: Journal of Nuclear Medicine Technology
Xiaoqing Yu, Xuefeng Wang
Even with the great advances in immunotherapy in recent years, the response rate to immune checkpoint inhibitor therapy for non-small cell lung cancer is only about 20%. We aimed to identify new features that would better predict which patients can benefit from an immune checkpoint blocker. This study is based on the publicly available gene expression data from The Cancer Genome Atlas lung cancer samples and the newly released mutation annotation data. We performed a comprehensive analysis by correlating patient cytolytic activity index, mutational signatures, and other immune characteristics in four stratified patient groups...
2018: PeerJ
Arthur Winer, J Nicholas Bodor, Hossein Borghaei
Immunotherapy has revolutionized the field of oncology. By inhibiting the cytotoxic T-lymphocyte-associated protein (CTLA-4) and programmed death-1 (PD-1) immune checkpoint pathways, multiple studies have demonstrated greatly improved survival in locally advanced and metastatic cancers including melanoma, renal, lung, gastric, and hepatocellular carcinoma. Trials in other malignancies are ongoing, and undoubtedly the number of drugs in this space will grow beyond the six currently approved by the Food and Drug Administration...
February 2018: Journal of Thoracic Disease
Suchita Pakkala, Taofeek K Owonikoko
Small cell lung cancer (SCLC) is a rapidly progressive cancer that often debilitates patients within months of detection and quickly becomes refractory to the limited options of therapy. While SCLC is not generally considered an immunogenic tumor, clinical experience suggests that patients with robust immune response manifesting as paraneoplastic syndrome are more likely to present with limited stage of the disease and tend to have a better prognosis. Monoclonal antibodies targeting critical negative regulators of immune response, so called immune checkpoints, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) have expanded the application of immune-based therapies to increasing number of advanced stage cancers...
February 2018: Journal of Thoracic Disease
Justin Yeh, Kristen A Marrone, Patrick M Forde
Lung cancer continues to be the leading cause of cancer death worldwide. Recently, immunotherapy for non-small cell lung cancer (NSCLC) has emerged as a powerful treatment option for advanced lung cancer. The relative success of programmed death 1 (PD-1) and/or programmed death ligand 1 (PD-L1) antibodies in metastatic disease have increased interest in expanding their use to earlier stage NSCLC. The complex and diverse nature of stage III disease also invites the incorporation of immunotherapy into treatment plans in both the neoadjuvant and consolidation settings...
February 2018: Journal of Thoracic Disease
Sandrine Niyongere, Andreas Saltos, Jhanelle E Gray
Immune checkpoint inhibitors enhance the activation and antitumor activity of the immune system, resulting in durable response rates in a select group of patients. Cytotoxic T lymphocyte antigen 4 (CTLA4) inhibitors target the inhibitory interaction between CTLA4 and CD80 or CD86. Programmed death 1 (PD1) inhibitors target the interaction between PD1 receptors on T-cells and PD-ligand 1 (PD-L1) and PD-ligand 2, blocking the inhibitory signaling and resulting in activation of T-cell effector function. These therapeutic drugs were originally evaluated in patients with metastatic melanoma before expansion to all tumor types, including non-small cell lung cancer (NSCLC) with promising results...
February 2018: Journal of Thoracic Disease
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