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Article ; Online: How the microenvironment wires the natural history of chronic lymphocytic leukemia.

Caligaris-Cappio, Federico / Bertilaccio, Maria T S / Scielzo, Cristina

2014 Volume 24, Page(s) 43–48

Abstract: The investigation on the mechanisms that govern the development and progression of cancer is constantly swaying between "seed" and "soil". Chronic lymphocytic leukemia (CLL) makes no exception. Its natural history, including response to treatment and ... ...

Abstract	The investigation on the mechanisms that govern the development and progression of cancer is constantly swaying between "seed" and "soil". Chronic lymphocytic leukemia (CLL) makes no exception. Its natural history, including response to treatment and drug resistance, is determined both by causal and influential genes and by the relationships that leukemic cells entertain with their supportive microenvironments. Therefore dissecting the role of microenvironment may provide new strategies of diagnosis and treatment. CLL, though phenotypically homogeneous, is clinically heterogeneous and despite major therapeutic advances remains incurable. Conceivably the host of new non-genotoxic drugs that operate at the forefront between tumor cells and their milieu will modify the present therapeutic perspective by re-shaping the tumor cell/microenvironment cross talk.
MeSH term(s)	Animals ; Carcinogenesis/genetics ; Cytoskeleton/genetics ; Disease Models, Animal ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Mice ; Signal Transduction ; Tumor Microenvironment
Language	English
Publishing date	2014-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1033980-2
ISSN	1096-3650 ; 1044-579X
ISSN (online)	1096-3650
ISSN	1044-579X
DOI	10.1016/j.semcancer.2013.06.010
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Article: Chronic lymphocytic leukemia: the pathologist's view of lymph node microenvironment.

Ponzoni, Maurilio / Doglioni, Claudio / Caligaris-Cappio, Federico

Seminars in diagnostic pathology

2011 Volume 28, Issue 2, Page(s) 161–166

Abstract: Chronic lymphocytic leukemia (CLL), an indolent B-cell malignancy frequently diagnosed in the elderly, is characterized by the relentless accumulation of CD5+ monoclonal B cells that proliferate in the appropriate tissue microenvironments. Despite many ... ...

Abstract	Chronic lymphocytic leukemia (CLL), an indolent B-cell malignancy frequently diagnosed in the elderly, is characterized by the relentless accumulation of CD5+ monoclonal B cells that proliferate in the appropriate tissue microenvironments. Despite many advances achieved by molecular and functional studies, our knowledge of the reciprocal relationship between the CLL cell and its microenvironment at the tissue level is still largely incomplete. In this review we present the relevant current information on the tissue microenvironmental features of CLL, focusing on the events that appear to occur in the lymph node. Special attention is devoted to analyzing the properties of both neoplastic and nonneoplastic bystander cells within proliferation centers, the mysterious structures that likely represent the actual proliferative compartment.
MeSH term(s)	Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Lymph Nodes/pathology ; Pathology ; Tumor Microenvironment
Language	English
Publishing date	2011-08-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	605834-6
ISSN	1930-1111 ; 0740-2570
ISSN (online)	1930-1111
ISSN	0740-2570
DOI	10.1053/j.semdp.2011.02.014
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Article ; Online: Lenalidomide enhances CD23.CAR T cell therapy in chronic lymphocytic leukemia.

Tettamanti, Sarah / Rotiroti, Maria Caterina / Giordano Attianese, Greta Maria Paola / Arcangeli, Silvia / Zhang, Ronghua / Banerjee, Priyanka / Galletti, Giovanni / McManus, Sheighlah / Mazza, Massimiliano / Nicolini, Fabio / Martinelli, Giovanni / Ivan, Cristina / Veliz Rodriguez, Tania / Barbaglio, Federica / Scarfò, Lydia / Ponzoni, Maurilio / Wierda, William / Gandhi, Varsha / Keating, Michael /

Biondi, Andrea / Caligaris-Cappio, Federico / Biagi, Ettore / Ghia, Paolo / Bertilaccio, Maria Teresa Sabrina

Leukemia & lymphoma

2022 Volume 63, Issue 7, Page(s) 1566–1579

Abstract: Chimeric antigen receptors (CAR)-modified T cells are an emerging therapeutic tool for chronic lymphocytic leukemia (CLL). However, in patients with CLL, well-known T-cell defects and the inhibitory properties of the tumor microenvironment (TME) hinder ... ...

Abstract	Chimeric antigen receptors (CAR)-modified T cells are an emerging therapeutic tool for chronic lymphocytic leukemia (CLL). However, in patients with CLL, well-known T-cell defects and the inhibitory properties of the tumor microenvironment (TME) hinder the efficacy of CAR T cells. We explored a novel approach combining CARs with lenalidomide, an immunomodulatory drug that tempers the immunosuppressive activity of the CLL TME. T cells from patients with CLL were engineered to express a CAR specific for CD23, a promising target antigen. Lenalidomide maintained the in vitro effector functions of CD23.CAR
MeSH term(s)	Humans ; Immunotherapy, Adoptive ; Interleukin Receptor Common gamma Subunit ; Lenalidomide/pharmacology ; Lenalidomide/therapeutic use ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell/therapy ; T-Lymphocytes ; Tumor Microenvironment
Chemical Substances	Interleukin Receptor Common gamma Subunit ; Lenalidomide (F0P408N6V4)
Language	English
Publishing date	2022-03-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2022.2043299
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Article ; Online: An overview of chronic lymphocytic leukaemia biology.

Bertilaccio, M T S / Scielzo, C / Muzio, M / Caligaris-Cappio, F

Best practice & research. Clinical haematology

2010 Volume 23, Issue 1, Page(s) 21–32

Abstract: Chronic lymphocytic leukaemia (CLL) is characterised by accumulation of CD5(+) monoclonal B cells in primary and secondary lymphoid tissues. Genetic defects and stimuli originating from the microenvironment concur to the selection and expansion of the ... ...

Abstract	Chronic lymphocytic leukaemia (CLL) is characterised by accumulation of CD5(+) monoclonal B cells in primary and secondary lymphoid tissues. Genetic defects and stimuli originating from the microenvironment concur to the selection and expansion of the malignant clone. Several lines of evidence, including molecular and functional analysis of the monoclonal immunoglobulin, support the hypothesis that stimulation through the B-cell receptor affects life and death of leukaemic cells. The microenvironment also has a critical role in the survival and accumulation of leukaemic cells within lymphoid organs where signals delivered from the surrounding cells are likely crucial in inducing proliferation. Nevertheless, several major biological issues still remain to be solved including regulation of the balance between proliferation and survival of leukaemic cells and the links between emerging gene abnormalities and microenvironment. In this context, mouse models are helpful tools in understanding disease mechanisms and in evaluating the efficacy of novel therapeutic agents.
MeSH term(s)	Animals ; Cell Proliferation ; Cell Survival ; Disease Models, Animal ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/metabolism ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Leukemia, Lymphocytic, Chronic, B-Cell/therapy
Language	English
Publishing date	2010-03
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2048027-1
ISSN	1532-1924 ; 1521-6926
ISSN (online)	1532-1924
ISSN	1521-6926
DOI	10.1016/j.beha.2009.12.005
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Article ; Online: Cohort Study to Assess the Impact of Breast Implants on Breastfeeding.

Filiciani, Sandra / Siemienczuk, Guillermo F / Nardín, Juan M / Cappio, Bárbara / Albertengo, Andrés C / Nozzi, Guillermo / Caggioli, Matías

Plastic and reconstructive surgery

2016 Volume 138, Issue 6, Page(s) 1152–1159

Abstract: Background: The objective of this study was to evaluate the impact of breast implant surgery and its approaches on lactation by comparing women with and without breast implants at the time of childbirth.: Methods: Between April of 2013 and July of ... ...

Abstract	Background: The objective of this study was to evaluate the impact of breast implant surgery and its approaches on lactation by comparing women with and without breast implants at the time of childbirth. Methods: Between April of 2013 and July of 2014, in Rosario (Sanatorio de la Mujer and Centro Quirúrgico Rosario), Argentina, a prospective cohort study of women with and without breast implants was performed. Of a total of 3950 births that occurred during this period, 200 patients with similar anthropometric characteristics (maternal and newborn) were selected. Breastfeeding (exclusive or mixed) was compared with artificial feeding at 24 and 48 hours and 30 days in both groups, and the type of incision was also compared. Results: Breastfeeding at 30 days showed a nonsignificant trend favoring the control group (OR, 7.39; 95 percent CI, 0.92 to 339.2). The percentage of women with implants who succeeded in establishing breastfeeding (exclusive or mixed) was very high (93 percent). In the control group, 99 percent of the women were breastfeeding at 30 days. In a comparison of the submammary and areola incision, breastfeeding showed odds ratios of 0.78 (95 percent CI, 0.33 to 1.87) at 24 hours, 1.10 (95 percent CI, 0.48 to 2.56) at 48 hours, and 0.18 (95 percent CI, 0.36 to 1.82) at 30 days. Conclusions: This study shows that most patients with breast implants were able to establish breastfeeding. However, there is a higher number of women without implants that established exclusive breastfeeding. No significant difference was found between the different surgical approaches. Clinical question/level of evidence: Therapeutic, II.
MeSH term(s)	Adult ; Breast Feeding/statistics & numerical data ; Breast Implantation/instrumentation ; Breast Implantation/methods ; Breast Implants ; Female ; Humans ; Infant ; Infant, Newborn ; Prospective Studies
Language	English
Publishing date	2016-10-27
Publishing country	United States
Document type	Journal Article ; Observational Study ; Video-Audio Media
ZDB-ID	208012-6
ISSN	1529-4242 ; 0032-1052 ; 0096-8501
ISSN (online)	1529-4242
ISSN	0032-1052 ; 0096-8501
DOI	10.1097/PRS.0000000000002745
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Zs.MO 293: Show issues

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Article: Biology of chronic lymphocytic leukemia.

Caligaris-Cappio, F

Reviews in clinical and experimental hematology

2001 Volume 4, Issue 1, Page(s) 5–21

Abstract: ... with progressive hypogammaglobulinemia; and (c) they have a high prevalence of autoimmune phenomena. Recent ...

Abstract	B-cell chronic lymphocytic leukemia (CLL) lies at the cross-roads of hematology, immunology and oncology for at least three major reasons: (a) it is the prototype of human malignancies that primarily involve defects in the induction of apoptosis; (b) CLL patients develop a severe immunodeficiency with progressive hypogammaglobulinemia; and (c) they have a high prevalence of autoimmune phenomena. Recent advances in the biology of the malignant cell in CLL lead to a scenario comprised of two basic elements: first, CLL cells are optimally organized to survive in their niches because their ability to undergo apoptosis is severely hampered; second, they have a microenvironment-dependence that promotes their extended survival, a situation that arises most probably through direct cell-to-cell contacts. In addition, CLL cells themselves are the major accessory cells in CLL, but are inefficient antigen-presenting cells. This latter defect may provide a clue to reinterpret the events of immunodeficiency and autoimmunity.
MeSH term(s)	Antigen-Presenting Cells/pathology ; Apoptosis/drug effects ; Apoptosis/immunology ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/immunology ; Cell Transformation, Neoplastic/pathology ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/etiology ; Leukemia, Lymphocytic, Chronic, B-Cell/immunology ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology
Language	English
Publishing date	2001-07-16
Publishing country	Italy
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2086903-4
ISSN	1825-151X ; 1127-0020
ISSN (online)	1825-151X
ISSN	1127-0020
DOI	10.1046/j.1468-0734.2000.00001.x
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Zs.A 5731: Show issues

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Article ; Online: iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL.

Hallek, Michael / Cheson, Bruce D / Catovsky, Daniel / Caligaris-Cappio, Federico / Dighiero, Guillermo / Döhner, Hartmut / Hillmen, Peter / Keating, Michael / Montserrat, Emili / Chiorazzi, Nicholas / Stilgenbauer, Stephan / Rai, Kanti R / Byrd, John C / Eichhorst, Barbara / O'Brien, Susan / Robak, Tadeusz / Seymour, John F / Kipps, Thomas J

Blood

2018 Volume 131, Issue 25, Page(s) 2745–2760

Abstract: The previous edition of the consensus guidelines of the International Workshop on Chronic Lymphocytic Leukemia (iwCLL), published in 2008, has found broad acceptance by physicians and investigators caring for patients with CLL. Recent advances including ... ...

Abstract	The previous edition of the consensus guidelines of the International Workshop on Chronic Lymphocytic Leukemia (iwCLL), published in 2008, has found broad acceptance by physicians and investigators caring for patients with CLL. Recent advances including the discovery of the genomic landscape of the disease, the development of genetic tests with prognostic relevance, and the detection of minimal residual disease (MRD), coupled with the increased availability of novel targeted agents with impressive efficacy, prompted an international panel to provide updated evidence- and expert opinion-based recommendations. These recommendations include a revised version of the iwCLL response criteria, an update on the use of MRD status for clinical evaluation, and recommendations regarding the assessment and prophylaxis of viral diseases during management of CLL.
MeSH term(s)	Clinical Trials as Topic ; Disease Management ; Genetic Testing/methods ; Humans ; Immunophenotyping/methods ; Karyotyping/methods ; Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Leukemia, Lymphocytic, Chronic, B-Cell/therapy ; Mutation ; Neoplasm Staging/methods ; Neoplasm, Residual/diagnosis ; Neoplasm, Residual/genetics ; Neoplasm, Residual/pathology ; Neoplasm, Residual/therapy ; Prognosis
Language	English
Publishing date	2018-03-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2017-09-806398
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Uh III Zs.140: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 364: Show issues

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Article ; Online: Xenograft models of chronic lymphocytic leukemia: problems, pitfalls and future directions.

Bertilaccio, M T S / Scielzo, C / Simonetti, G / Ten Hacken, E / Apollonio, B / Ghia, P / Caligaris-Cappio, F

Leukemia

2013 Volume 27, Issue 3, Page(s) 534–540

Abstract: Xenotransplantation of human tumor cells into immunodeficient mice has been a powerful preclinical tool in several hematological malignancies, with the notable exception of chronic lymphocytic leukemia (CLL). For several decades, this possibility was ... ...

Abstract	Xenotransplantation of human tumor cells into immunodeficient mice has been a powerful preclinical tool in several hematological malignancies, with the notable exception of chronic lymphocytic leukemia (CLL). For several decades, this possibility was hampered by the inefficient and/or short-term engrafment of CLL cells into available animals. The development of new generations of immunocompromised mice has allowed to partially overcome these constraints. Novel humanized animal models have been created that allow to recapitulate the pathogenesis of the disease and the complex in vivo relationships between leukemic cells and the microenvironment. In this review we discuss the development of xenograft models of CLL, how they may help elucidating the mechanisms that account for the natural history of the disease and facilitating the design of novel therapeutic approaches.
MeSH term(s)	Animals ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell/etiology ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Mice ; Transplantation, Heterologous ; Xenograft Model Antitumor Assays
Language	English
Publishing date	2013-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/leu.2012.268
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Zs.A 2295: Show issues

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Article ; Online: Noise model application to small hydroelectrical power plants impact evaluation in the Aosta Valley territory.

Tibone, C / Agnesod, G / Cappio Borlino, M / Tartin, C / Crea, D / Berlier, F

Radiation protection dosimetry

2009 Volume 137, Issue 3-4, Page(s) 271–274

Abstract: In this paper measurements, results and model estimates, with reference to hydroelectric power plant noise emissions in the Aosta Valley territory, are compared in different contexts. The analysis was performed to evaluate and point out the influence of ... ...

Abstract	In this paper measurements, results and model estimates, with reference to hydroelectric power plant noise emissions in the Aosta Valley territory, are compared in different contexts. The analysis was performed to evaluate and point out the influence of the noise source context on the accuracy of the model results. The estimates were implemented considering power plants as: point sources and area sources taking (or not) into account the building elements of the plant. This method allowed evaluating the detail that is suitable to achieve in an estimate and to justify possible simplifications in this kind of noise source description. Noise measurements were carried out simultaneously, at different distances from the power plants that were taken into account. The measurement results at the closest points to the sources were used as the model input data, while the levels found at the other points were used for comparison with the estimate results.
MeSH term(s)	Computer Simulation ; Environmental Exposure/analysis ; Environmental Exposure/statistics & numerical data ; Italy ; Models, Theoretical ; Noise ; Power Plants/statistics & numerical data ; Radiation Dosage ; Radiation Monitoring/methods ; Radiation Monitoring/statistics & numerical data
Language	English
Publishing date	2009-12
Publishing country	England
Document type	Evaluation Studies ; Journal Article
ZDB-ID	225912-6
ISSN	1742-3406 ; 0144-8420
ISSN (online)	1742-3406
ISSN	0144-8420
DOI	10.1093/rpd/ncp213
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Article ; Online: IL1R8 Deficiency Drives Autoimmunity-Associated Lymphoma Development.

Riva, Federica / Ponzoni, Maurilio / Supino, Domenico / Bertilaccio, Maria Teresa Sabrina / Polentarutti, Nadia / Massara, Matteo / Pasqualini, Fabio / Carriero, Roberta / Innocenzi, Anna / Anselmo, Achille / Veliz-Rodriguez, Tania / Simonetti, Giorgia / Anders, Hans-Joachim / Caligaris-Cappio, Federico / Mantovani, Alberto / Muzio, Marta / Garlanda, Cecilia

Cancer immunology research

2019 Volume 7, Issue 6, Page(s) 874–885

Abstract: Chronic inflammation, including that driven by autoimmunity, is associated with the development of B-cell lymphomas. IL1R8 is a regulatory receptor belonging to the IL1R family, which negatively regulates NF-κB activation following stimulation of IL1R or ...

Abstract	Chronic inflammation, including that driven by autoimmunity, is associated with the development of B-cell lymphomas. IL1R8 is a regulatory receptor belonging to the IL1R family, which negatively regulates NF-κB activation following stimulation of IL1R or Toll-like receptor family members. IL1R8 deficiency is associated with the development of severe autoimmune lupus-like disease in
MeSH term(s)	Animals ; Autoimmunity/genetics ; Biomarkers ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/immunology ; Cell Transformation, Neoplastic/metabolism ; Disease Models, Animal ; Disease Susceptibility ; Gene Expression ; Genetic Predisposition to Disease ; Humans ; Immunoglobulin Heavy Chains/genetics ; Immunohistochemistry ; Lymphoma/etiology ; Lymphoma/metabolism ; Lymphoma/pathology ; Lymphoma, Large B-Cell, Diffuse/etiology ; Lymphoma, Large B-Cell, Diffuse/metabolism ; Lymphoma, Large B-Cell, Diffuse/pathology ; Mice ; NF-kappa B/metabolism ; Receptors, Interleukin-1/deficiency ; Signal Transduction ; Toll-Like Receptors/metabolism
Chemical Substances	Biomarkers ; Immunoglobulin Heavy Chains ; NF-kappa B ; Receptors, Interleukin-1 ; SIGIRR protein, human ; Toll-Like Receptors
Language	English
Publishing date	2019-04-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2732489-8
ISSN	2326-6074 ; 2326-6066
ISSN (online)	2326-6074
ISSN	2326-6066
DOI	10.1158/2326-6066.CIR-18-0698
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