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1. Defining the critical hurdles in cancer immunotherapy

Author

Andrea Nicolini, Francesco M. Marincola, William E. Carson, Paolo A. Ascierto, Michele Maio, Jedd D. Wolchok, Michael T. Lotze, Jirina Bartunkova, Weihua Xiao, Hauke Winter, Barbara Seliger, Jon M. Wigginton, Cedrik M. Britten, Ignacio Melero, Guido Kroemer, Neil L. Berinstein, Jill O'Donnell-Tormey, Heinz Zwierzina, Lothar Bergmann, Lloyd J. Old, Christian H. Ottensmeier, Jérôme Galon, Per thor Straten, Koji Kawakami, Michael Papamichail, Yutaka Kawakami, Michael I. Nishimura, Mary L. Disis, Steinar Aamdal, C. J. M. Melief, Pedro Romero, Kristen Hege, Wenru Song, Pawel Kalinski, Jonathan L. Bramson, Harpreet Singh-Jasuja, Jens Peter Marschner, Bernard A. Fox, Samir N. Khleif, Brad H. Nelson, Marij J. P. Welters, Elizabeth M. Jaffee, Patrick Hwu, Rik J. Scheper, Robert C. Rees, Giuseppe Masucci, Hideaki Tahara, Cristina Bonorino, Glenn Dranoff, Ernest C. Borden, William J. Murphy, Zhigang Tian, Michael B. Atkins, Robert O. Dillman, Thomas F. Gajewski, Hiroshi Shiku, Leif Håkansson, Michael J. Mastrangelo, Lisa H. Butterfield, Shukui Qin, Laurence Zitvogel, Harry Dolstra, Michele Guida, George Coukos, Mohamed L. Salem, Xuetao Cao, Giorgio Parmiani, Enrico Proietti, Ena Wang, Sylvia Janetzki, A. Raja Choudhury, Gerd Ritter, Hyam I. Levitsky, Kunle Odunsi, Kohzoh Imai, Paul von Hoegen, Christoph Huber, Réjean Lapointe, Antoni Ribas, Dolores J. Schendel, Pamela S. Ohashi, Beatrix Kotlan, Cécile Gouttefangeas, James H. Finke, Alfred E. Chang, Howard L. Kaufman, Lindy G. Durrant, Sjoerd H. van der Burg, Jared Gollob, Dainius Characiejus, Tara Withington, Padmanee Sharma, Ronald B. Herberman, Cristina Maccalli, Ulrich Keilholtz, Axel Hoos, Graham Pawelec, Fabio Grizzi, Tanja D. de Gruijl, F. Stephen Hodi, Ruggero Ridolfi, James P. Allison, Licia Rivoltini, Carl H. June, Rolf Kiessling, Department of Molecular Microbiology and Immunology, Oregon Health and Science University [Portland] (OHSU)-Knight Cancer Institute, Earle A. Chiles Research Institute, Providence Portland Medical Center-Robert W. Franz Research Center-Providence Cancer Center, Clinical Cooperation Group 'Immune Monitoring', German Research Center for Environmental Health-Helmholtz Centre Munich-Institute of Molecular Immunology, Division of Hematology Oncology, University of Pittsburgh Cancer Institute-Departments of Medicine, Department of Surgery, Cancer Institute-University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Department of Immunology, University of Pittsburgh Cancer Institute, Department of Clinical Cancer Research, The Norwegian Radium Hospital-Oslo University Hospital [Oslo], Memorial Sloane Kettering Cancer Center [New York], Howard Hughes Medical Institute (HHMI), Medical Oncology and Innovative Therapy, Instituto Nazionale Tumori-Fondazione 'G. Pascale', Beth Israel Deaconess Medical Center, Harvard Medical School [Boston] (HMS), Institute of Immunology, Charles University [Prague] (CU)-FOCIS Center of Excellence-2nd Medical School, Goethe-Universität Frankfurt am Main, IRX Therapeutics, Stanford University-ImmunoVaccine Inc., Instituto Nacional para o Controle do Câncer, Instituto de Pesquisas Biomédicas-PUCRS Faculdade de Biociências, Department of Solid Tumor Oncology, Cleveland Clinic, Department of Translational Hematology and Oncology Research, Department of Pathology, McMaster University [Hamilton, Ontario], University Medical Center Mainz, III. Medical Department, Ribological GmbH, Department of Medicine-University Medical Center of the Johannes Gutenberg-University-Clinical Development, BioNTech AG, Chinese Academy of Medical Sciences, Second Military Medical University-National Key Laboratory of Medical Immunology, Ohio State University [Columbus] (OSU), University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Institute of Oncology, Vilnius University [Vilnius]-Faculty of Medicine, Department of Medicine, University of Queensland [Brisbane], Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Department of Medical Oncology, VU Medical Center-Cancer Center Amsterdam, Hoag Institute for Research and Education, Hoag Cancer Institute, Department of Laboratory Medicine, Radboud university [Nijmegen]-Nijmegen Centre for Molecular Life Sciences-Nijmegen Medical Centre [Nijmegen], Brigham and Women's Hospital [Boston], Dana-Farber Cancer Institute [Boston], Academic Department of Clinical Oncology, University of Nottingham, UK (UON), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Alnylam Pharmaceuticals, Inc., Institute for Cell Biology, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Oncology Department, University of Lund, CanImGuide Therapeutics AB, University of California [San Francisco] (UCSF), University of California, Intrexon Corporation, Germantown, Bristol-Myers Squibb Company, Translational Oncology & Immunology, Centre TRON at the Mainz University Medical Center, Department of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center [Houston], The Institute of Medical Science, The University of Tokyo (UTokyo), Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine [Baltimore]-Johns Hopkins University School of Medicine [Baltimore], ZellNet Consulting, Pathology and Laboratory Medicine, University of Pennsylvania [Philadelphia], Rush University Cancer Center, Rush University Medical Center [Chicago], School of Medicine and Public Health, Kyoto University [Kyoto], Division of Cellular Signaling, Institute for Advanced Medical Research, Dept. of Hematology and Medical Oncology, Charité Comprehensive Cancer Center, Cancer Vaccine Section, NCI, Department of Oncology - Pathology, Cancer Center Karolinska [Karolinska Institutet] (CCK), Karolinska Institutet [Stockholm]-Karolinska Institutet [Stockholm], Department of Molecular Immunology and Toxicology, Center of Surgical and Molecular Tumor pathology, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), School of Medicine, Johns Hopkins University (JHU)-Oncology Center, Department of Molecular Oncology, Foundation San Raffaele Scientific Institute, Medical Oncology and Immunotherapy, Istituto Toscano Tumori-University Hospital of Siena-Department of Oncology, Merck KGaA, Merck & Co. Inc, Thomas Jefferson University, Department of Oncology-Pathology, karolinska institute, CIMA, CUN and Medical School University of Navarra, Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Davis Medical Center, Sacramento-University of California, Deeley Research Centre, BC Cancer Agency (BCCRC), Department of Internal Medicine, University of Pisa - Università di Pisa, Oncology Institute, Loyola University Medical Center (LUMC)-Cardinal Bernardin Cancer Center, Tumor Immunology and Immunotherapy Program, Roswell Park Cancer Institute [Buffalo]-Department of Gynecologic Oncology, Ontario Cancer Institute, University Health Network, Cancer Immunotherapy Consortium (CIC), Cancer Research Institute, Cancer Research, Ludwig Institute, Experimental Cancer Medicine Centre, University of Southampton-Faculty of Medicine, Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Unit of Immuno-Biotherapy of Melanoma and Solid Tumors, San Raffaele Scientific Institute, Center for Medical Research, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita', Chinese PLA Cancer Center, Department of Oncology-The Eighty-First Hospital, The John van Geest Cancer Research Centre, School of Science and Technology-Nottingham Trent University, Jonsson Comprehensive Cancer Center, Immunoterapia e Terapia Cellulare Somatica, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Unit of Immunotherapy of Human Tumors, Istituto Nazionale Tumori-IRCCS Foundation, Division of Clinical Onco-Immunology, Université de Lausanne (UNIL)-Ludwig Center for Cancer Research, Immunology and Biotechnology Unit, Faculty of Science-Department of Zoology-Tanta University, VU University Medical Center [Amsterdam], Institute of Medical Immunology, Martin-Luther-Universität Halle Wittenberg (MLU), Departments of Immunology, Department of Cancer Vaccine, Mie University, Department of Immuno-gene Therapy, Immatics Biotechnologies GmbH, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen-Department of Immunology-Institute for Cell Biology, Millennium: The Takeda Oncology Company, Pfizer Oncology, Center for Cancer Immune Therapy (CCIT), Herlev and Gentofte Hospital-Department of Hematology, Department of Surgery and Bioengineering, The University of Tokyo (UTokyo)-Institute of Medical Science-Advanced Clinical Research Center, School of Life Sciences-University of Science & Technology of China [Suzhou], Institute of Immunopharmacology & Immunotherapy, Shandong University-School of Pharmaceutical Sciences, Experimental Cancer Immunology and Therapy, Leiden University Medical Center (LUMC)-Department of Clinical Oncology, Euraccine Consulting Group, Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine-Clinical Center-National Institute of Health NIH), Center for Human Immunology (CHI), National Institute of Health (NIH), Leiden University Medical Center (LUMC)-Department of Clinical Oncology (K1-P), Ludwig Maximilians University-Klinikum Grosshadern, Biological Therapy of Cancer, Medical and Surgical Services Organizations-International Society For Biological Therapy Of Cancer, School of Life Science-University of Science and Technology of China [Hefei] (USTC), Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Department Haematology and Oncology, Innsbruck Medical University [Austria] (IMU), Medical Center, University of Chicago, Discovery Medicine-Oncology, Tumor Vaccine Group, University of Washington [Seattle]-Center for Translational Medicine in Women's Health, The work of CIMT-CIP was supported by a grant from the Wallace Coulter foundation (Florida, USA)., Helmholtz Centre Munich-Institute of Molecular Immunology-Helmholtz Zentrum München = German Research Center for Environmental Health, University of Pennsylvania-University of Pennsylvania, Radboud University [Nijmegen]-Nijmegen Centre for Molecular Life Sciences-Nijmegen Medical Centre [Nijmegen], Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Lund University [Lund], University of California [San Francisco] (UC San Francisco), University of California (UC), University of Pennsylvania, Kyoto University, Sacramento-University of California (UC), Université de Lausanne = University of Lausanne (UNIL)-Ludwig Center for Cancer Research, Klinikum Grosshadern-Ludwig-Maximilians University [Munich] (LMU), University of Science and Technology of China [Hefei] (USTC)-School of Life Science, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), BMC, Ed., Computer Systems, Medical oncology laboratory, Pathology, CCA - Immuno-pathogenesis, CCA - Innovative therapy, Oregon Health and Science University-Knight Cancer Institute, Cancer Institute-University of Pittsburgh, The Norwegian Radium Hospital-Oslo University Hospital, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, Howard Hughes Medical Institute, Ludwig Center for Cancer Immunotherapy, A Teaching Hospital of Harvard Medical School, Charles University [Prague]-FOCIS Center of Excellence-2nd Medical School, Stanford University [Stanford]-ImmunoVaccine Inc., Ohio State University [Columbus] ( OSU ), University of Michigan Medical Center, University of Pennsylvania Medical Center, Radboud university [Nijmegen]-Nijmegen Centre for Molecular Life Sciences-Nijmegen Medical Centre, University of Nottingham, UK ( UON ), Cleveland Clinic Foundation, Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Istituto Clinico Humanitas [Milan] ( IRCCS Milan ), Humanitas University [Milan] ( Hunimed ), University of California [San Francisco] ( UCSF ), Harvard Medical School [Boston] ( HMS ), MD Anderson Cancer Center, The University of Tokyo, Rush University Medical Center, Cancer Center Karolinska [Karolinska Institutet] ( CCK ), Centre Hospitalier de l'Université de Montréal-Hôpital Notre-Dame Research Center ( CRCHUM ), Department of Medicine-University of Montreal, Johns Hopkins University ( JHU ) -Oncology Center, BC Cancer Agency ( BCCRC ), University of Pisa [Pisa], Loyola University Medical Center ( LUMC ) -Cardinal Bernardin Cancer Center, Cancer Immunotherapy Consortium ( CIC ), University of Southampton [Southampton]-Faculty of Medicine, Eberhard Karls Universität Tübingen, University of Lausanne-Ludwig Center for Cancer Research, Martin-Luther-University Halle-Wittenberg, Mie University Graduate School of Medicine, Eberhard Karls Universität Tübingen-Department of Immunology-Institute for Cell Biology, Center for Cancer Immune Therapy ( CCIT ), Herlev Hospital-Department of Hematology, The University of Tokyo-Institute of Medical Science-Advanced Clinical Research Center, Infectious Disease and Immunogenetics Section ( IDIS ), Center for Human Immunology ( CHI ), University of Science and Technology of China [Hefei] ( USTC ) -School of Life Science, Immunologie des tumeurs et immunothérapie ( UMR 1015 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Innsbruck Medical University [Austria] ( IMU ), Department of Medicine-Clinical Development, BioNTech AG-Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Universiteit Leiden-Universiteit Leiden, Roswell Park Cancer Institute [Buffalo] (RPCI)-Department of Gynecologic Oncology, Istituto Superiore di Sanità (ISS), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Universiteit Leiden-Universiteit Leiden-Department of Clinical Oncology, and Universiteit Leiden-Universiteit Leiden-Department of Clinical Oncology (K1-P)

Subjects
medicine.medical_specialty, International Cooperation, medicine.medical_treatment, Alternative medicine, lcsh:Medicine, Translational research, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cancer Immunotherapy, General Biochemistry, Genetics and Molecular Biology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Translational Research, Biomedical, 03 medical and health sciences, SDG 17 - Partnerships for the Goals, 0302 clinical medicine, Cancer immunotherapy, [SDV.CAN] Life Sciences [q-bio]/Cancer, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Neoplasms, medicine, Humans, In patient, 030304 developmental biology, Medicine(all), 0303 health sciences, geography, Summit, geography.geographical_feature_category, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Biochemistry, Genetics and Molecular Biology(all), business.industry, lcsh:R, Cancer, General Medicine, Public relations, medicine.disease, 3. Good health, Clinical trial, Immunotherapy, Neoplasms/therapy, Translational Medical Research, 030220 oncology & carcinogenesis, Immunology, Commentary, Working group, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer. © 2011 Fox et al; licensee BioMed Central Ltd.

Published
2011
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2. Prognostic impact of B-cell density in cutaneous melanoma.

Author

Ladányi A, Kiss J, Mohos A, Somlai B, Liszkay G, Gilde K, Fejös Z, Gaudi I, Dobos J, and Tímár J

Subjects
Adolescent, Adult, Aged, B-Lymphocytes pathology, Female, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Lymphocytes, Tumor-Infiltrating pathology, Male, Melanoma mortality, Melanoma pathology, Middle Aged, Prognosis, Proportional Hazards Models, Skin Neoplasms mortality, Skin Neoplasms pathology, T-Lymphocytes immunology, T-Lymphocytes pathology, Young Adult, B-Lymphocytes immunology, Lymphocytes, Tumor-Infiltrating immunology, Melanoma immunology, Skin Neoplasms immunology
Abstract

Studies on the prognostic importance of tumor-infiltrating lymphocytes have mainly focused on T cells, while little is known about the role of tumor-infiltrating B lymphocytes. We investigated the prevalence of CD20(+) B cells by immunohistochemistry in primary melanoma samples of 106 patients and analyzed in relation to clinicopathological parameters and patients' survival. The majority of samples contained a significant amount of B lymphocytes, predominantly dispersed in the stroma surrounding tumor deposits (mean peritumoral and intratumoral densities: 178.7 ± 156.1 vs. 4.9 ± 6.9 cells/mm², respectively). B cells organized in follicle-like aggregates were also observed in 26% of the samples. B-cell density correlated with that of activated (CD25(+) or OX40(+)) T lymphocytes. Infiltration by CD20(+) lymphocytes did not correlate with tumor thickness, while the presence of B-cell aggregates was observed more frequently in thick melanomas. On the other hand, B-cell infiltration was more pronounced in nonmetastatic or lymph node metastatic tumors, compared to visceral metastatic ones. Accordingly, high number of these cells provided significant survival advantage (P = 0.0391 and P = 0.0136 for intra- and peritumoral infiltration, respectively). Furthermore, combination of peritumoral B-cell density with the number of activated T lymphocytes identified patient subgroups with different disease outcome, which was most favorable in the case of high density, while very poor in the case of low density of both cell types. Multivariate survival analysis identified tumor thickness and CD20(+)/OX40(+) cell density combination as significant independent prognostic factors. Taken together, our results show correlation between low number of CD20(+) B lymphocytes and melanoma progression, indicating a possible role of tumor-infiltrating B cells in antitumoral immune response. It was also reflected in better outcome of the disease since the density of B lymphocytes alone as well as in combination with that of activated T cells proved of prognostic importance in patients with malignant melanoma.

Published
2011
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3. Glucocorticoid receptor expression and antiproliferative effect of dexamethasone on human melanoma cells.

Author

Dobos J, Kenessey I, Tímár J, and Ladányi A

Subjects
Apoptosis, Case-Control Studies, Cell Proliferation, Flow Cytometry, Humans, Immunoenzyme Techniques, Melanoma pathology, Nevus metabolism, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Skin metabolism, Tumor Cells, Cultured, Dexamethasone pharmacology, Glucocorticoids pharmacology, Melanoma drug therapy, Melanoma metabolism, Receptors, Glucocorticoid genetics, Receptors, Glucocorticoid metabolism
Abstract

Glucocorticoids, such as dexamethasone are widely used in cancer therapy and have cell type-specific pro- or antiapoptotic effects. We examined whether melanoma cells are sensitive to dexamethasone treatment. We have demonstrated for the first time that in human melanoma cell lines as well as in benign and malignant melanocytic tumors glucocorticoid receptor (GCR) is present both at mRNA and protein level. Dexamethasone applied at high doses inhibited the in vitro growth of WM983A human melanoma cells. The inhibitory effect was due to apoptosis induction. In the case of this relatively sensitive cell line dexamethasone enhanced the effect of the chemotherapeutic drug DTIC.

Published
2011
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4. Pioneering the trail of cancer immunotherapy.

Author

Kotlan B and Balwit JM

Subjects
Antibodies, Monoclonal therapeutic use, Humans, Immunotherapy, Neoplasms therapy
Abstract

The annual conference of the International Society for Biological Therapy of Cancer (iSBTc), recently renamed the Society for Immunotherapy of Cancer (SITC), provides clinicians and scientists with a uniquely broad yet focused view of the growing field of tumor immunology and cancer immunotherapy. In this time of exciting new developments in cancer immunotherapy, it is critically important to effectively guide new immune-based advances from bench to bedside to improve outcomes of patients with cancer. iSBTc/SITC with its dedicated leadership (past and present) provides this guidance through its Annual Meeting and associated programs. This year the society celebrated its 25th Anniversary in Hyatt Regency Washington on Capitol Hill (Washington DC, USA), with educational offerings from 30 September to 4 October 2010.

Published
2011
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5. FOXP3+ cell density in primary tumor has no prognostic impact in patients with cutaneous malignant melanoma.

Author

Ladányi A, Mohos A, Somlai B, Liszkay G, Gilde K, Fejos Z, Gaudi I, and Tímár J

Subjects
Adult, Aged, Biomarkers, Tumor analysis, Female, Forkhead Transcription Factors biosynthesis, Humans, Immunohistochemistry, Male, Melanoma mortality, Melanoma pathology, Middle Aged, Neoplasm Staging, Prognosis, Skin Neoplasms mortality, Skin Neoplasms pathology, T-Lymphocytes, Regulatory metabolism, Biomarkers, Tumor immunology, Forkhead Transcription Factors immunology, Melanoma immunology, Skin Neoplasms immunology, T-Lymphocytes, Regulatory immunology
Abstract

Regulatory T cells (Tregs) have been implicated as inhibitors of antitumor immune reactions. However, data on the relevance of their prevalence at tumor sites in influencing disease outcome are controversial. The aim of our study was to investigate the role in tumor progression and the prognostic impact of the density of lymphocytes expressing FOXP3, a transcription factor expressed predominantly by CD4(+)CD25(+) Tregs, in primary cutaneous melanoma. We examined the infiltration of FOXP3(+) cells by immunohistochemistry in tumor samples from 97 patients and evaluated in relation to patient and tumor parameters. The degree of infiltration by FOXP3(+) cells did not show correlation with the thickness of melanomas. Moreover, no associations were found with metastasis formation during the 5-year follow-up period, patient survival, or any other clinicopathologic parameters studied. These results suggest that the presence of FOXP3(+) lymphocytes in primary tumors is not of prognostic importance in human cutaneous melanoma.

Published
2010
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6. Turning laboratory findings into therapy: a marathon goal that has to be reached.

Author

Kotlan B, Stroncek DF, and Marincola FM

Subjects
Biomedical Research trends, Chemistry, Clinical trends, Evidence-Based Medicine trends, Humans, Interdisciplinary Communication, Pharmaceutical Preparations, Research Design, Biomedical Research organization & administration, Chemistry, Clinical organization & administration, Evidence-Based Medicine organization & administration
Abstract

The mission of translational research involves difficult tasks to be accomplished for its ultimate goal, i.e., the introduction of novel, effective therapeutic strategies in the clinic to diminish human suffering and cure life-threatening diseases. Translational research (also referred to as translational medicine) facilitates the translation of investment in biomedical research into successful medical treatment. This includes the transfer of diagnostic and therapeutic advances by proving their efficacy in large evidence-based trials. Through the study of humans novel insights about disease are brought back to the laboratory to identify new, observation-based strategies. This "two-way road" ("bench to bedside and bedside to bench") process includes formulating guidelines for drug development and principles for new therapeutic strategies; initiating clinical investigations that provide the biological basis for new therapies, and related clinical trials; defining therapeutic targets and clinical endpoints. It requires a systematic approach beginning with specimen sampling, patient data collection, laboratory investigations, data analysis, preclinical testing, clinical trials, treatment efficacy monitoring, and finally the evaluation of therapeutic result. The marathon well symbolizes the enormous efforts undertaken by clinicians, scientists, regulators, ethicists, patient advocates, drug developers, and others, coordinately attempting to overcome obstacles along this road toward the final "marathon goal in medicine".

Published
2009

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