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https://www.readbyqxmd.com/read/28822058/immune-dysfunction-in-non-hodgkin-lymphoma-avenues-for-new-immunotherapy-based-strategies
#1
REVIEW
Lorenzo Falchi
PURPOSE OF THIS REVIEW: The present review focuses on key aspects of non-Hodgkin lymphoma (NHL) evasion of immune surveillance and how these can be leveraged to devise effective immunotherapy strategies. RECENT FINDINGS: In recent years, significant progress has been made in the field of cancer immunotherapy. In particular, the remarkable clinical results of anti-programmed death (PD)-1/PD-ligand (L)1 antibodies are revolutionizing the treatment approach to multiple solid and hematologic tumors...
August 18, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28820000/novel-combination-strategies-for-enhancing-efficacy-of-immune-checkpoint-inhibitors-in-the-treatment-of-metastatic-solid-malignancies
#2
Michael J Flynn, James M G Larkin
Immune-checkpoint inhibitor (ICPI) drugs, which include antibodies against CTLA-4, PD-1 and PD-L1, have been shown to induce durable complete responses in a proportion of patients with particular efficacy demonstrated in both the first line and refractory setting in advanced NSCLC and melanoma. However, these drugs remain effective only in a minority of unselected patients. Areas covered: This review will focus on mechanisms of resistance to ICPI and underline the importance of identification of novel predictive markers of responsiveness...
August 18, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28819209/synergistic-immuno-photothermal-nanotherapy-symphony-for-the-treatment-of-unresectable-and-metastatic-cancers
#3
Yang Liu, Paolo Maccarini, Gregory M Palmer, Wiguins Etienne, Yulin Zhao, Chen-Ting Lee, Xiumei Ma, Brant A Inman, Tuan Vo-Dinh
Metastatic spread is the mechanism in more than 90 percent of cancer deaths and current therapeutic options, such as systemic chemotherapy, are often ineffective. Here we provide a proof of principle for a novel two-pronged modality referred to as Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) having the potential to safely eradicate both primary tumors and distant metastatic foci. Using a combination of immune-checkpoint inhibition and plasmonic gold nanostar (GNS)-mediated photothermal therapy, we were able to achieve complete eradication of primary treated tumors and distant untreated tumors in some mice implanted with the MB49 bladder cancer cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28815043/the-mek-inhibitor-selumetinib-complements-ctla-4-blockade-by-reprogramming-the-tumor-immune-microenvironment
#4
Edmund Poon, Stefanie Mullins, Amanda Watkins, Geoffrey S Williams, Jens-Oliver Koopmann, Gianfranco Di Genova, Marie Cumberbatch, Margaret Veldman-Jones, Shaun E Grosskurth, Vasu Sah, Alwin Schuller, Corrine Reimer, Simon J Dovedi, Paul D Smith, Ross Stewart, Robert W Wilkinson
BACKGROUND: T-cell checkpoint blockade and MEK inhibitor combinations are under clinical investigation. Despite progress elucidating the immuno-modulatory effects of MEK inhibitors as standalone therapies, the impact of MEK inhibition on the activity of T-cell checkpoint inhibitors remains incompletely understood. Here we sought to characterize the combined effects of MEK inhibition and anti-CTLA-4 mAb (anti-CTLA-4) therapy, examining effects on both T-cells and tumor microenvironment (TME)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28812378/bevacizumab-in-advanced-lung-cancer-state-of-the-art
#5
Sandra Assoun, Solenn Brosseau, Christelle Steinmetz, Valérie Gounant, Gérard Zalcman
Despite recent advances in metastatic lung cancer treatment with the advent of immune checkpoint inhibitors and molecules targeting addictive genomic abnormalities, prognosis of most of the patients remains unfavorable. Combination approaches with older drugs, such as bevacizumab, should be thus envisioned. Bevacizumab is a monoclonal anti-VEGF antibody, approved by the US FDA and the EMA in first-line and maintenance settings of advanced nonsquamous non-small-cell lung cancer (NSCLC) treatment, in association with platinum-based chemotherapy...
August 16, 2017: Future Oncology
https://www.readbyqxmd.com/read/28807001/the-mek-inhibitor-selumetinib-complements-ctla-4-blockade-by-reprogramming-the-tumor-immune-microenvironment
#6
Edmund Poon, Stefanie Mullins, Amanda Watkins, Geoffrey S Williams, Jens-Oliver Koopmann, Gianfranco Di Genova, Marie Cumberbatch, Margaret Veldman-Jones, Shaun E Grosskurth, Vasu Sah, Alwin Schuller, Corrine Reimer, Simon J Dovedi, Paul D Smith, Ross Stewart, Robert W Wilkinson
BACKGROUND: T-cell checkpoint blockade and MEK inhibitor combinations are under clinical investigation. Despite progress elucidating the immuno-modulatory effects of MEK inhibitors as standalone therapies, the impact of MEK inhibition on the activity of T-cell checkpoint inhibitors remains incompletely understood. Here we sought to characterize the combined effects of MEK inhibition and anti-CTLA-4 mAb (anti-CTLA-4) therapy, examining effects on both T-cells and tumor microenvironment (TME)...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28777142/assessing-tumor-infiltrating-lymphocytes-in-solid-tumors-a-practical-review-for-pathologists-and-proposal-for-a-standardized-method-from-the-international-immunooncology-biomarkers-working-group-part-1-assessing-the-host-immune-response-tils-in-invasive-breast
#7
Shona Hendry, Roberto Salgado, Thomas Gevaert, Prudence A Russell, Tom John, Bibhusal Thapa, Michael Christie, Koen van de Vijver, M V Estrada, Paula I Gonzalez-Ericsson, Melinda Sanders, Benjamin Solomon, Cinzia Solinas, Gert G G M Van den Eynden, Yves Allory, Matthias Preusser, Johannes Hainfellner, Giancarlo Pruneri, Andrea Vingiani, Sandra Demaria, Fraser Symmans, Paolo Nuciforo, Laura Comerma, E A Thompson, Sunil Lakhani, Seong-Rim Kim, Stuart Schnitt, Cecile Colpaert, Christos Sotiriou, Stefan J Scherer, Michail Ignatiadis, Sunil Badve, Robert H Pierce, Giuseppe Viale, Nicolas Sirtaine, Frederique Penault-Llorca, Tomohagu Sugie, Susan Fineberg, Soonmyung Paik, Ashok Srinivasan, Andrea Richardson, Yihong Wang, Ewa Chmielik, Jane Brock, Douglas B Johnson, Justin Balko, Stephan Wienert, Veerle Bossuyt, Stefan Michiels, Nils Ternes, Nicole Burchardi, Stephen J Luen, Peter Savas, Frederick Klauschen, Peter H Watson, Brad H Nelson, Carmen Criscitiello, Sandra O'Toole, Denis Larsimont, Roland de Wind, Giuseppe Curigliano, Fabrice André, Magali Lacroix-Triki, Mark van de Vijver, Federico Rojo, Giuseppe Floris, Shahinaz Bedri, Joseph Sparano, David Rimm, Torsten Nielsen, Zuzana Kos, Stephen Hewitt, Baljit Singh, Gelareh Farshid, Sibylle Loibl, Kimberly H Allison, Nadine Tung, Sylvia Adams, Karen Willard-Gallo, Hugo M Horlings, Leena Gandhi, Andre Moreira, Fred Hirsch, Maria V Dieci, Maria Urbanowicz, Iva Brcic, Konstanty Korski, Fabien Gaire, Hartmut Koeppen, Amy Lo, Jennifer Giltnane, Marlon C Rebelatto, Keith E Steele, Jiping Zha, Kenneth Emancipator, Jonathan W Juco, Carsten Denkert, Jorge Reis-Filho, Sherene Loi, Stephen B Fox
Assessment of tumor-infiltrating lymphocytes (TILs) in histopathologic specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitors and other forms of immunotherapy become a clinical reality, the need for widely applicable, accessible, and reliable immunooncology biomarkers is clear. In part 1 of this review we briefly discuss the host immune response to tumors and different approaches to TIL assessment...
September 2017: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28689001/immuno-oncologic-approaches-car-t-cells-and-checkpoint-inhibitors
#8
REVIEW
Francesca Gay, Mattia D'Agostino, Luisa Giaccone, Mariella Genuardi, Moreno Festuccia, Mario Boccadoro, Benedetto Bruno
Advances in understanding myeloma biology have shown that disease progression is not only the consequence of intrinsic tumor changes but also of interactions between the tumor and the microenvironment in which the cancer grows. The immune system is an important component of the tumor microenvironment in myeloma, and acting on the immune system is an appealing new treatment strategy. There are 2 ways to act toward immune cells and boost antitumor immunity: (1) to increase antitumor activity (acting on T and NK cytotoxic cells), and (2) to reduce immunosuppression (acting on myeloid-derived stem cells and T regulatory cells)...
June 17, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28668860/gastrocutaneous-fistula-in-a-patient-with-locally-recurrent-msi-high-colorectal-cancer-local-complications-arising-from-therapeutic-response-to-immune-checkpoint-blockade
#9
Claire Greene, Eric K Nakakura, Andrew H Ko
Colorectal cancers with high microsatellite instability (MSI-H) have distinct clinical features in terms of their prognosis, recurrence patterns, and sensitivity to immunotherapeutic agents. We present the case of a woman with a left-sided MSI-H colon cancer who had repeated recurrences concentrated exclusively in the left upper quadrant of the abdomen, including gastric involvement. Despite multiple surgical resections, radiation, and several lines of chemotherapy, her disease eventually eroded through the chest wall...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28666979/predicting-the-response-to-ctla-4-blockade-by-longitudinal-noninvasive-monitoring-of-cd8-t-cells
#10
Mohammad Rashidian, Jessica R Ingram, Michael Dougan, Anushka Dongre, Katherine A Whang, Camille LeGall, Juan J Cragnolini, Brian Bierie, Monica Gostissa, James Gorman, Gijsbert M Grotenbreg, Atul Bhan, Robert A Weinberg, Hidde L Ploegh
Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non-small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno-positron emission tomography (immuno-PET) can visualize tumors by detecting infiltrating lymphocytes and, through longitudinal observation of individual animals, distinguish responding tumors from those that do not respond to therapy. We used (89)Zr-labeled PEGylated single-domain antibody fragments (VHHs) specific for CD8 to track the presence of intratumoral CD8(+) T cells in the immunotherapy-susceptible B16 melanoma model in response to checkpoint blockade...
August 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28665052/discovery-of-breast-putative-cancer-antigens-using-an-integrative-platform-of-genomics-driven-immunoproteomics
#11
Veneta Qendro, Deborah H Lundgren, Samuel Palczewski, Poornima Hegde, Christina Stevenson, Laurie Perpetua, Ardian Latifi, Jesse Merriman, Grace Bugos, David K Han
Recent advances in cancer immuno-therapeutics such as checkpoint inhibitors, chimeric antigen-receptor T cells, and tumor infiltrating T cells (TIL) are now significantly impacting cancer patients in a positive manner. Although very promising, reports indicate no more than 25% of cases result in complete remission. One of the limitations of these treatments is the identity of putative cancer antigens in each patient as it is technically challenging to identify of cancer antigens in a rapid fashion. Thus, identification of cancer antigens followed by targeted treatment will increase the efficacy of cancer immunotherapies...
June 30, 2017: Proteomics
https://www.readbyqxmd.com/read/28663235/immunotherapy-of-prostate-cancer-facts-and-hopes
#12
Marijo Bilusic, Ravi A Madan, James L Gulley
In the last few years immunotherapy has become an important cancer treatment modality and while the principles of immunotherapy evolved over many decades, the FDA approvals of sipuleucel-T and ipilimumab began a new wave in immuno-oncology. Despite the current enthusiasm, it is unlikely that any of the immunotherapeutics alone can dramatically change prostate cancer outcomes, but combination strategies are more promising and provide a reason for optimism. Several completed and ongoing studies have shown that the combination of cancer vaccines or checkpoint inhibitors with different immunotherapeutic agents, hormonal therapy (enzalutamide), radiation therapy (radium 223), DNA-damaging agents (olaparib), or chemotherapy (docetaxel) can enhance immune responses and induce more dramatic, long-lasting clinical responses without significant toxicity...
June 29, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28634022/goals-and-objectives-of-the-italian-network-for-tumor-biotherapy-nibit
#13
Vincenzo Russo, Alberto Amadori, Marco Bregni, Luana Calabrò, Mario Paolo Colombo, Massimo Di Nicola, Pier Francesco Ferrucci, Enrico Proietti, Michele Maio, Matteo Bellone
The explosion in the immuno-oncology field, exemplified by the clinical implementation of immune checkpoint inhibitor blockade and other immunotherapeutic strategies was quickly recognized by the Italian biomedical community, thanks to the networking activities of the Italian Network for Tumor Biotherapy (NIBIT), which has been active since 2004 in the diffusion of new scientific and clinical findings in the fields of tumor immunology and immunotherapy. Numerous activities of NIBIT have also helped to overcome the hurdles associated with the clinical implementation of cancer immune-biotherapeutic strategies at the national and international levels...
June 16, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28603207/varied-immuno-related-adverse-events-induced-by-immune-check-point-inhibitors-nivolumab-associated-psoriasiform-dermatitis-related-with-increased-serum-level-of-interleukin-6
#14
Naoko Okiyama, Ryota Tanaka
  Nivolumab is a standard recombinant antibody treatment for patients with malignant melanoma (MM), which functions as an immune checkpoint inhibitor by blocking the programmed cell death-1 (PD-1) pathway in T cells. However, it leads to various immune-related adverse events (irAEs), and also exacerbates underlying autoimmune diseases. Herein we report cases of MM with irAE. Case 1: A 69-year-old woman with MM developed destructive thyroiditis resulting in hypothyroidism after 3 doses of nivolumab, and had been treated with thyroid gland auxiliary therapy...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28600479/trabectedin-overrides-osteosarcoma-differentiative-block-and-reprograms-the-tumor-immune-environment-enabling-effective-combination-with-immune-checkpoint-inhibitors
#15
Chiara Ratti, Laura Botti, Valeria Cancila, Silvia Galvan, Ilaria Torselli, Cecilia Garofalo, Maria Cristina Manara, Lucia Bongiovanni, Cesare F Valenti, Alessia Burocchi, Mariella Parenza, Barbara Cappetti, Sabina Sangaletti, Claudio Tripodo, Katia Scotlandi, Mario P Colombo, Claudia Chiodoni
Purpose: Osteosarcoma (OS), the most common primary bone tumor, is characterized by an aggressive behavior with high tendency to develop lung metastases as well as by multiple genetic aberrations that have hindered the development of targeted therapies. New therapeutic approaches are urgently needed; however, novel combinations with immunotherapies and checkpoint inhibitors require suitable preclinical models with intact immune systems to be properly tested. <p>Experimental Design: We have developed immuno-competent OS models that grow orthotopically in the bone and spontaneously metastasize to the lungs, mimicking human OS...
June 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28578991/oncolytic-vsv-primes-differential-responses-to-immuno-oncology-therapy
#16
Nicholas M Durham, Kathy Mulgrew, Kelly McGlinchey, Noel R Monks, Hong Ji, Ronald Herbst, JoAnn Suzich, Scott A Hammond, Elizabeth J Kelly
Vesicular stomatitis virus encoding the IFNβ transgene (VSV-IFNβ) is a mediator of potent oncolytic activity and is undergoing clinical evaluation for the treatment of solid tumors. Emerging preclinical and clinical data suggest treatment of tumors with oncolytic viruses may sensitize tumors to checkpoint inhibitors and increase the anti-tumor immune response. New generations of immuno-oncology molecules including T cell agonists are entering clinical development and could be hypothesized to enhance the activity of oncolytic viruses, including VSV-IFNβ...
August 2, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28546465/quantitative-mass-spectrometry-analysis-of-pd-l1-protein-expression-n-glycosylation-and-expression-stoichiometry-with-pd-1-and-pd-l2-in-human-melanoma
#17
Carlos A Morales-Betanzos, Hyoungjoo Lee, Paula I Gonzalez-Ericsson, Justin M Balko, Douglas B Johnson, Lisa J Zimmerman, Daniel C Liebler
Quantitative assessment of key proteins that control the tumor-immune interface is one of the most formidable analytical challenges in immunotherapeutics. We developed a targeted mass spectrometry (MS) platform to quantify programmed cell death-1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2) at fmol/microgram protein levels in formalin fixed, paraffin-embedded sections from 22 human melanomas. PD-L1 abundance ranged 50-fold, from approximately 0.03 to 1.5 fmol/microgram protein and the PRM data were largely concordant with total PD-L1-positive cell content, as analyzed by immunohistochemistry (IHC) with the E1L3N antibody...
May 25, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28497159/current-status-of-chimeric-antigen-receptor-engineered-t-cell-based-and-immune-checkpoint-blockade-based-cancer-immunotherapies
#18
REVIEW
Upendra P Hegde, Bijay Mukherji
Adoptive cell therapies with chimeric antigen receptor (CAR) engineered T cells (CAR-T) and immune checkpoint inhibition (ICI)-based cancer immunotherapies have lately shown remarkable success in certain tumor types. CAR-T cell-based therapies targeting CD19 can now induce durable remissions as well as prolong disease-free survival of patients with CD19 positive treatment refractory B cell malignancies and ICI-based therapies with humanized monoclonal antibodies against the T cell inhibitory receptors CTLA-4 and PD-1 as well as against the PD-1 ligand, PD-L1, can now achieve durable remissions as well as prolongation of life of a sizeable fraction of patients with melanoma and Hodgkin's lymphoma and non-small cell cancers...
May 11, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28459041/advancing-cancer-therapy-with-present-and-emerging-immuno-oncology-approaches
#19
REVIEW
Jeff Kamta, Maher Chaar, Anusha Ande, Deborah A Altomare, Sihem Ait-Oudhia
Immuno-oncology (I-O) is a young and growing field on the frontier of cancer therapy. Contrary to cancer therapies that directly target malignant cells, I-O therapies stimulate the body's immune system to target and attack the tumor, which is otherwise invisible to, or inhibiting the immune response. To this end, several methods have been developed: First, passive therapies that enable T-cells to fight the tumor without direct manipulation, typically through binding and modifying the intracellular signaling of surface receptors...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28446466/landscape-of-combination-immunotherapy-and-targeted-therapy-to-improve-cancer-management
#20
Leandro M Colli, Mitchell J Machiela, Han Zhang, Timothy A Myers, Lea Jessop, Olivier Delattre, Kai Yu, Stephen J Chanock
Cancer treatments composed of immune checkpoint inhibitors and oncogene-targeted drugs might improve cancer management, but there has been little investigation of their combined potential as yet. To estimate the fraction of cancer cases that might benefit from such combination therapy, we conducted an exploratory study of cancer genomic datasets to determine the proportion with somatic mutation profiles amenable to either immunotherapy or targeted therapy. We surveyed 13,349 genomic profiles from public databases for cases with specific mutations targeted by current agents or a burden of exome-wide nonsynonymous mutations (NsM) that exceed a proposed threshold for response to checkpoint inhibitors...
July 1, 2017: Cancer Research
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