International Journal of Molecular Sciences

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Dr. Gerardo Musuraca

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IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) S.r.l., Via Piero Maroncelli, 40-47014 Meldola, FC, Italy
Interests: Lymphoma; Lymphoproliferative disorders; T Cells against cancer; Immunotherapies; Th17 in hematologic diseases

Special Issue Information

Dear Colleagues,

Chronic Lymphoproliferative diseases are the most frequent haematological diseases in adults and despite the treatments currently in use, the percentages of patients who do not respond to treatment and die are still high. The immune system of these patients is often severely compromised by the chemotherapies used, but above all by the diseases themselves and yet little is known about what influences its permissiveness to the tumor and its escape.

In fact, the important role of immunotherapy and reactivation of the immune system is being re-understood, as a weapon to allow targeted treatment of the tumor and its constant immunocontrol until eradication.

This Special Issue aims to explore the correlations between chronic lymphoproliferative diseases and the immunological microenvironment, the immune system at the molecular and cellular level, its pathogenetic role and its therapeutic implications. Clinical studies with immunological/molecular aspects, experimental studies in in vitro and in vivo models, review articles as well, are all welcome for consideration.

Dr. Gerardo Musuraca
Guest Editor

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Keywords

lymphoma
T cell
immuntherapies
lymphoproliferative disease
myeloma

Published Papers (2 papers)

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Research

17 pages, 5571 KiB

Open AccessArticle

Follicular Lymphoma Microenvironment Traits Associated with Event-Free Survival

by Maria Maddalena Tumedei, Filippo Piccinini, Irene Azzali, Francesca Pirini, Sara Bravaccini, Serena De Matteis, Claudio Agostinelli, Gastone Castellani, Michele Zanoni, Michela Cortesi, Barbara Vergani, Biagio Eugenio Leone, Simona Righi, Anna Gazzola, Beatrice Casadei, Davide Gentilini, Luciano Calzari, Francesco Limarzi, Elena Sabattini, Andrea Pession, Marcella Tazzari and Clara Bertuzzi Show full author list Hide full author list

Int. J. Mol. Sci. 2023, 24(12), 9909; https://doi.org/10.3390/ijms24129909 - 8 Jun 2023

Cited by 1 | Viewed by 1568

Abstract

The majority of patients with Follicular Lymphoma (FL) experience subsequent phases of remission and relapse, making the disease “virtually” incurable. To predict the outcome of FL patients at diagnosis, various clinical-based prognostic scores have been proposed; nonetheless, they continue to fail for a subset of patients. Gene expression profiling has highlighted the pivotal role of the tumor microenvironment (TME) in the FL prognosis; nevertheless, there is still a need to standardize the assessment of immune-infiltrating cells for the prognostic classification of patients with early or late progressing disease. We studied a retrospective cohort of 49 FL lymph node biopsies at the time of the initial diagnosis using pathologist-guided analysis on whole slide images, and we characterized the immune repertoire for both quantity and distribution (intrafollicular, IF and extrafollicular, EF) of cell subsets in relation to clinical outcome. We looked for the natural killer (CD56), T lymphocyte (CD8, CD4, PD1) and macrophage (CD68, CD163, MA4A4A)-associated markers. High CD163/CD8 EF ratios and high CD56/MS4A4A EF ratios, according to Kaplan–Meier estimates were linked with shorter EFS (event-free survival), with the former being the only one associated with POD24. In contrast to IF CD68+ cells, which represent a more homogeneous population, higher in non-progressing patients, EF CD68+ macrophages did not stratify according to survival. We also identify distinctive MS4A4A+CD163-macrophage populations with different prognostic weights. Enlarging the macrophage characterization and combining it with a lymphoid marker in the rituximab era, in our opinion, may enable prognostic stratification for low-/high-grade FL patients beyond POD24. These findings warrant validation across larger FL cohorts. Full article

(This article belongs to the Special Issue Molecular Advances in Lymphoproliferative Diseases)

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15 pages, 4447 KiB

Open AccessArticle

Reduced Percentage of CD14^dimCD16⁺SLAN⁺ Monocytes Producing TNF and IL-12 as an Immunological Sign of CLL Progression

by Wioleta Kowalska, Michał Zarobkiewicz, Waldemar Tomczak, Justyna Woś, Izabela Morawska and Agnieszka Bojarska-Junak

Int. J. Mol. Sci. 2022, 23(6), 3029; https://doi.org/10.3390/ijms23063029 - 11 Mar 2022

Cited by 3 | Viewed by 2193

Abstract

Monocytes are one of the least studied immune cells with a potentially important role in the pathogenesis of chronic lymphocytic leukemia (CLL). Nevertheless, data regarding the role of subpopulations of monocytes in the CLL microenvironment are still limited. For the very first time, this study presents an assessment of monocyte subsets divided according to SLAN and CD16 expression in CLL patients. The study involved 70 freshly diagnosed CLL patients and 35 healthy donors. Using flow cytometry, monocyte subpopulations were assessed among PBMCs. CD14⁺ monocytes can be divided into: “classical” (CD14⁺CD16⁻SLAN⁻), “intermediate” (CD14⁺CD16⁺SLAN⁻) and “non-classical” (CD14^dimCD16⁺SLAN⁺). In our study, we noted an increased percentage of non-classical monocytes with intracellular expression of TNF and IL-12. On the other hand, among the intermediate monocytes, a significantly higher percentage of cells synthesizing anti-inflammatory IL-10 was detected. The percentage of CD14^dimCD16⁺SLAN⁺ monocytes producing TNF and IL-12 decreased with the stage of CLL and inversely correlated with the expression of the prognostic factors ZAP-70 and CD38. Moreover, the percentage of CD14^dimCD16⁺SLAN⁺ monocytes producing TNF and IL-12 was lower in CLL patients requiring treatment. This may indicate the beneficial effect of non-classical monocytes on the anti-tumor response. Full article

(This article belongs to the Special Issue Molecular Advances in Lymphoproliferative Diseases)

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