K Mikhail V. Kiselevsky i s e Editor l e v s k y E d . Atlas Eff ectors (cid:2) of Anti-Tumor A t l a s Immunity E f e c t o r s o f A n t i - T u m o r I m m u n i t y (cid:5)(cid:6)(cid:4) Atlas Effectors of Anti-Tumor Immunity Atlas Effectors of Anti-Tumor Immunity Editor Mikhail V. Kiselevsky NN Blokhin Russian Cancer Research Center RAMS, Moscow, Russia Editor MikhailV.Kiselevsky LaboratoryofCellImmunity NNBlokhinRussianCancer ResearchCenter RussianAcademyofMedicalSciences Kashirskoeshosse24 Moscow Russia115478 ISBN: 978-1-4020-6930-7 e-ISBN: 978-1-4020-6931-4 LibraryofCongressControlNumber:2007939885 ©2008SpringerScience+BusinessMediaB.V. Nopartofthisworkmaybereproduced,storedinaretrievalsystem,ortransmitted inanyformorbyanymeans,electronic,mechanical,photocopying,microfilming,recording orotherwise,withoutwrittenpermissionfromthePublisher,withtheexception ofanymaterialsuppliedspecificallyforthepurposeofbeingentered andexecutedonacomputersystem,forexclusiveusebythepurchaserofthework. Printedonacid-freepaper. 9 8 7 6 5 4 3 2 1 springer.com Table of Contents Preface vii List of Contributors ix 1. Adoptive immunotherapy for human cancers: Flagmen signal first “open road” then “roadblocks.” A narrative synopsis 1 Joseph G. Sinkovics 2. Tumor microenvironment genesis and implications on cancer immune response 25 Gianfranco Baronzio and Isabel Freitas 3. Natural killer cells. Lymphokine-activated killers 45 Irina Zh. Shubina, Olga V. Lebedinskaya, Evgenia O. Khalturina, Irina O. Chikileva and Mikhail V. Kiselevsky 4. CD4+/CD25+ T-regulatory cells 65 Irina Zh. Shubina, Nadezhda P. Velizheva and Mikhail V. Kiselevsky 5. CD8+ CD57+ T cells in tumor immunology 73 María I. Sada-Ovalle 6. Natural killer T (NKT) cells: Immunophenotype, functional characteristics and significance in clinical practice 81 Olga V. Lebedinskaya, Nelly K. Akchmatova, Irina O. Chikileva, Irina Zh. Shubina and Mikhail V. Kiselevsky 7. LAK immunotherapy in clinical studies 101 Irina Zh. Shubina, Lev V. Demidov, Irina O. Chikileva, Olga V. Lebedinskaya and Mikhail V. Kiselevsky v vi Table of Contents 8. Major properties of dendritic cells and their actual and potential applications in cancer therapy and infectious disease prophylaxis 111 Irina O. Chikileva, Natalia Yu. Anisimova, Olga V. Lebedinskaya, Mikhail V. Kiselevsky and Vyacheslav M. Abramov Index 161 Preface Traditional understanding of anti-tumor of anti-tumor defense is assigned to other immunity is based on the theory of immuno- effectors of innate immunity as well, first logical surveillance and it suggests function of all, as potential NK activators, such as of cytotoxic lymphocytes that can recognize dendriticcellsandnaturalkillerT-cells.Along tumor-specific antigens and lyse malig- withthementionedfunctionsinnateimmunity nantly transformed cells. However tumor effectors can have a negative regulatory effect development is not the direct result of on anti-tumor immuno-biological surveillance immune system disorders and even in by secreting Th2 cytokines. Contemporary case of marked immuno-deficiencies, in standpoints in understanding mechanisms of particular, in patients – transplant recipients, innate and adaptive immunity are the basis immune dysfunction does not always lead for development and improvement various to higher cancer incidence comparing with methods of adoptive immunotherapy. total population. This phenomenon may be Anti-tumor immunity has been subject of explained by the concept of immuno-editing, most thorough interest and detailed investi- which suggests that anti-tumor immunity gation over the last decades. Nowadays more effectors can not only protect the organism and more specialists in medicine and adjacent from tumor development, but also select low areas face the problem of immuno-biological immunogenic clones of transformed cells that surveillance function. Research data on this can escape from immuno-biological surveil- issue are diverse and extensive. In numerous lance. Mechanism of avoiding the immune monographs, educational books and scien- attack is primarily due to the lack of tific papers a keen reader can find practi- specific antigens on tumor cell surface and cally any material concerning the questions loss or down-regulation of expression rate of interest. The purpose of the present of molecules of major histocompatibility publication is to convey considerably full complex, which are necessary factors for and up-to-date information to the reader initiation of adaptive immune response and in a reasonably comprehensible format. To generation of antigen-specific T-lymphocytes. make the material easy for perception the Therefore recent data have more often given Atlas has a large number of illustrative evidence in favor of innate immunity being pictures,whichalsohelptotrackinterrelations themainweaponofimmunesurveillanceover between morphological features of anti-tumor tumordevelopment.AndNKsplaythecrucial immunity effectors and their phenotype and role as they can recognize and lyse trans- functional characteristics. The Atlas is aimed formedcellsinMHCandantigenindependent at a wide audience of students and teachers manner. An important part in realization of medical and biology faculties, specialists vii viii Preface of research laboratories and diagnostics The Atlas comprises over 200 figures and centers, practicing oncologists and immunol- schemes referring to effectors of anti-tumor ogists, as well as physicians of different immunityandmethodsofanti-canceradoptive specializations. immunotherapy. List of Contributors Vyacheslav M. Abramov Mikhail V. Kiselevsky Institute Immunological Engineering Moscow Region, NN Blokhin Russian Cancer Research Center RAMS, Russia Laboratory of Cell Immunity, Moscow, Russia Nelly K. Akchmatova Olga V. Lebedinskaya II Metchnikov Research Institute of Vaccines and EAVagner Perm Medical Academy, Departtament of Serums, Laboratory of Therapeutic Vaccines, Histology, Embryology and Cytology Perm, Russia Moscow, Russia María I. Sada-Ovalle Nathalie Yu. Anisimova Research Unit, Biochemistry Department, National NN Blokhin Russian Cancer Research Center RAMS, Institute of Respiratory Diseases, Calzada de Tlalpan Laboratory of Cell Immunity, Moscow, Russia 4502, Col. Sección XVI, Delegación Tlalpan, México D.F., Mexico Gianfranco Baronzio Family Medicine Area ASL1 Legnano (Mi) and Irina Zh. Shubina Radiotherapy, Hyperthermia Service, Policlinico di Monza, Monza, Italy NN Blokhin Russian Cancer Research Center RAMS, Moscow, Russia Irina O. Chikileva NN Blokhin Russian Cancer Research Center RAMS, Joseph G. Sinkovics Laboratory of Cell Immunity, Moscow, Russia St.Joseph’sHospital’sCancerInstituteAffiliatedwith the H. L. Moffitt Comprehensive Cancer Center at the Lev V. Demidov University of South Florida College of Medicine; NN Blokhin Russian Cancer Research Center RAMS, Department of Medical Microbiology & Immunology, Department of Biotherapy, Moscow, Russia the University of South Florida College of Medicine, Tampa FL, USA Isabel Freitas University of Pavia, Department of Animal Biology Nadezhda P. Velizheva and IGM-CNR Center for Histochemistry and NN Blokhin Russian Cancer Research Center RAMS, Cytometry, Pavia, Italy Moscow, Russia Evgenia O. Khalturina I.M. Setchenov Medical Academy, Departtament of Microbiology, Virusology and Immunology Moscow, Russia ix The Atlas Effectors of Anti-Tumor Immunity activity is associated with the development was published with the financial support of of international science projects. Since 1994, The International Science and Technology the ISTC has managed financial support Center (ISTC). Chapters 3–8 have been exceeding USD 769M to 2500 projects, written by the participants of ISTC-supported encompassing over 70,000 scientists and projects. This publication has been produced technicians at more than 700 institutes in with the financial assistance of the European Russia and CIS. The ISTC also provides a Union as a Funding Party to the Agreement tax and customs-duty exempt mechanism for establishing the ISTC. its 370 commercial and governmental agency The International Science and Technology Partners to fund research with ISTC benefi- Center is an intergovernmental organization ciary institutes. 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