Publications by authors named "Michela Cangemi"

8 Publications

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Radical Hemithoracic Radiotherapy Induces Systemic Metabolomics Changes That Are Associated with the Clinical Outcome of Malignant Pleural Mesothelioma Patients.

Cancers (Basel) 2021 Jan 29;13(3). Epub 2021 Jan 29.

Immunopathology and Cancer Biomarkers Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.

Radical hemithoracic radiotherapy (RHRT) represents an advanced therapeutic option able to improve overall survival of malignant pleural mesothelioma patients. This study aims to investigate the systemic effects of this radiotherapy modality on the serum metabolome and their potential implications in determining the individual clinical outcome. Nineteen patients undergoing RHRT at the dose of 50 Gy in 25 fractions were enrolled. Serum targeted metabolomics profiles were investigated at baseline and the end of radiotherapy by liquid chromatography and tandem mass spectrometry. Univariate and multivariate OPLS-DA analyses were applied to study the serum metabolomics changes induced by RHRT while PLS regression analysis to evaluate the association between such changes and overall survival. RHRT was found to affect almost all investigated metabolites classes, in particular, the amino acids citrulline and taurine, the C14, C18:1 and C18:2 acyl-carnitines as well as the unsaturated long chain phosphatidylcholines PC ae 42:5, PC ae 44:5 and PC ae 44:6 were significantly decreased. The enrichment analysis showed arginine metabolism and the polyamine biosynthesis as the most perturbed pathways. Moreover, specific metabolic changes encompassing the amino acids and acyl-carnitines resulted in association with the clinical outcome accounting for about 60% of the interpatients overall survival variability. This study highlighted that RHRT can induce profound systemic metabolic effects some of which may have a significant prognostic value. The integration of metabolomics in the clinical assessment of the malignant pleural mesothelioma could be useful to better identify the patients who can achieve the best benefit from the RHRT treatment.
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http://dx.doi.org/10.3390/cancers13030508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866164PMC
January 2021

Serum albumin concentrations are associated with disease severity and outcomes in coronavirus 19 disease (COVID-19): a systematic review and meta-analysis.

Clin Exp Med 2021 Jan 28. Epub 2021 Jan 28.

Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43, 07100, Sassari, Italy.

Coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the most threatening pandemic in modern history. The aim of this systematic review and meta-analysis was to investigate the associations between serum albumin concentrations and COVID-19 disease severity and adverse outcomes. A systematic literature search was conducted in PubMed, from inception to October 30, 2020. Sixty-seven studies in 19,760 COVID-19 patients (6141 with severe disease or poor outcome) were selected for analysis. Pooled results showed that serum albumin concentrations were significantly lower in patients with severe disease or poor outcome (standard mean difference, SMD: - 0.99 g/L; 95% CI, - 1.11 to - 0.88, p < 0.001). In multivariate meta-regression analysis, age (t =  - 2.13, p = 0.043), publication geographic area (t = 2.16, p = 0.040), white blood cell count (t =  - 2.77, p = 0.008) and C-reactive protein (t =  - 2.43, p = 0.019) were significant contributors of between-study variance. Therefore, lower serum albumin concentrations are significantly associated with disease severity and adverse outcomes in COVID-19 patients. The assessment of serum albumin concentrations might assist with early risk stratification and selection of appropriate care pathways in this group.
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http://dx.doi.org/10.1007/s10238-021-00686-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842395PMC
January 2021

Clinical and Antitumor Immune Responses in Relapsed/Refractory Follicular Lymphoma Patients after Intranodal Injections of IFNα-Dendritic Cells and Rituximab: a Phase I Clinical Trial.

Clin Cancer Res 2019 09 6;25(17):5231-5241. Epub 2019 Jun 6.

Institute of Translational Pharmacology, CNR, Rome, Italy.

Purpose: This study was aimed at evaluating the feasibility, safety, immunologic and clinical responses in patients with follicular lymphoma treated with monocyte-derived dendritic cells generated in the presence of IFNα and GM-CSF (IFN-DC) in combination with low doses of rituximab.

Patients And Methods: Firstly, we analyzed and the immunologic properties of IFN-DC against follicular lymphoma. Thus, we performed a phase I trial in 8 patients with refractory and relapsed follicular lymphoma based on sequential intranodal injections of low-dose of rituximab and unloaded IFN-DC and report the safety, clinical, and immunologic results of the enrolled patients.

Results: Preclinical studies indicated that IFN-DC can synergize with rituximab leading to increased cytotoxicity and T-cell tumor infiltration. The clinical evaluation showed that the combined treatment was totally safe. The overall response rate was 50%, PET-negative complete response rate 37%, and remission is still ongoing in 2/4 of responding patients (median follow-up 26 months, range 11-47). Notably, following the combined therapy all patients showed induction/enhancement of T-cell responses by CD107 degranulation or IFNγ ELISPOT assay against patient-specific tumor IGHV sequences.

Conclusions: These results represent the proof-of-principle on the effectiveness of unloaded IFN-DC in inducing durable clinical responses and promoting induction of tumor-specific peripheral T cells, thus suggesting the occurrence of an effective endogenous antitumor vaccination. The overall findings indicate that some unique properties of IFN-DC can be successfully exploited to induce/enhance antitumor responses, thus representing a valuable antitumor strategy for novel and more effective combination therapies in patients with cancer.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-0709DOI Listing
September 2019

Dissecting the Multiplicity of Immune Effects of Immunosuppressive Drugs to Better Predict the Risk of Malignancies in Solid Organ Transplant Patients.

Front Oncol 2019 27;9:160. Epub 2019 Mar 27.

Translational Research Institute, University of Queensland Diamantina Institute, Brisbane, QLD, Australia.

malignancies constitute an emerging cause of morbidity after solid organ transplant (SOT), significantly affecting the long-term survival of transplant recipients. Pharmacologic immunosuppression may functionally impair the immunosurveillance in these patients, thereby increasing the risk of cancer development. Nevertheless, the multiplicity and heterogeneity of the immune effects induced by immunosuppressive drugs limit the current possibilities to reliably predict the risk of malignancy in SOT patients. Therefore, there is the pressing need to better characterize the immune dysfunctions induced by the different immunosuppressive regimens administered to prevent allograft rejection to tailor more precisely the therapeutic schedule and decrease the risk of malignancies. We herein highlight the impact exerted by different classes of immunosuppressants on the most relevant immune cells, with a particular focus on the effects on dendritic cells (DCs), the main regulators of the balance between immunosurveillance and tolerance.
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http://dx.doi.org/10.3389/fonc.2019.00160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445870PMC
March 2019

Fighting Viral Infections and Virus-Driven Tumors with Cytotoxic CD4 T Cells.

Front Immunol 2017 27;8:197. Epub 2017 Feb 27.

Istituto Oncologico Veneto IOV-IRCCS, Padova, Italy; Department of Surgery, Oncology and Gastroenterology, Oncology and Immunology Section, University of Padova, Padova, Italy.

CD4 T cells have been and are still largely regarded as the orchestrators of immune responses, being able to differentiate into distinct T helper cell populations based on differentiation signals, transcription factor expression, cytokine secretion, and specific functions. Nonetheless, a growing body of evidence indicates that CD4 T cells can also exert a direct effector activity, which depends on intrinsic cytotoxic properties acquired and carried out along with the evolution of several pathogenic infections. The relevant role of CD4 T cell lytic features in the control of such infectious conditions also leads to their exploitation as a new immunotherapeutic approach. This review aims at summarizing currently available data about functional and therapeutic relevance of cytotoxic CD4 T cells in the context of viral infections and virus-driven tumors.
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http://dx.doi.org/10.3389/fimmu.2017.00197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5327441PMC
February 2017

Cytokine-Induced Killer Cells Kill Chemo-surviving Melanoma Cancer Stem Cells.

Clin Cancer Res 2017 May 4;23(9):2277-2288. Epub 2016 Nov 4.

Division of Medical Oncology, Experimental Cell Therapy, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Torino, Italy.

The MHC-unrestricted activity of cytokine-induced killer (CIK) cells against chemo-surviving melanoma cancer stem cells (mCSC) was explored, as CSCs are considered responsible for chemoresistance and relapses. Putative mCSCs were visualized by engineering patient-derived melanoma cells (MC) with a lentiviral vector encoding eGFP under expression control by stemness gene promoter Their stemness potential was confirmed by limiting dilution assays. We explored the sensitivity of eGFP mCSCs to chemotherapy (CHT), BRAF inhibitor (BRAFi) or CIK cells, as single agents or in sequence, First, we treated MCs with fotemustine or dabrafenib (BRAF-mutated cases); then, surviving MCs, enriched in mCSCs, were challenged with autologous CIK cells. CIK cell activity against chemoresistant mCSCs was confirmed in two distinct immunodeficient murine models. We visualized eGFP mCSCs (14% ± 2.1%) in 11 MCs. The tumorigenic precursor rate was higher within eGFP MCs (1/42) compared with the eGFP counterpart (1/4,870). mCSCs were relatively resistant to CHT and BRAFi, but killed by CIK cells ( = 11, 8/11 autologous), with specific lysis ranging from 95% [effector:tumor ratio (E:T), 40:1] to 20% (E:T 1:3). infusion of autologous CIK cells into mice bearing xenografts from three distinct melanomas demonstrated significant tumor responses involving CHT-spared eGFP mCSCs ( = 0.001). Sequential CHT-immunotherapy treatment retained antitumor activity ( = 12, = 0.001) reducing mCSC rates ( = 0.01). These findings are the first demonstration that immunotherapy with CIK cells is active against autologous mCSCs surviving CHT or BRAFi. An experimental platform for mCSC study and rationale for CIK cells in melanoma clinical study is provided. .
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http://dx.doi.org/10.1158/1078-0432.CCR-16-1524DOI Listing
May 2017

Cytokine-induced killer cells as immunotherapy for solid tumors: current evidence and perspectives.

Immunotherapy 2015 27;7(9):999-1010. Epub 2015 Aug 27.

Department of Oncology, University of Torino, Turin, Italy.

Cytokine-induced killer (CIK) cells are ex vivo expanded T lymphocytes endowed with potent MHC-independent antitumor activity. CIK cells are emerging as promising therapeutic approach in the field of cancer adoptive immunotherapy, with biologic features favoring their transferability into clinical applications. Aim of this review is to present the biologic characteristic of CIK cells, discussing the main preclinical findings and initial clinical applications in the field of solid tumors.
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http://dx.doi.org/10.2217/imt.15.61DOI Listing
August 2016

Adoptive immunotherapy against sarcomas.

Expert Opin Biol Ther 2015 Apr 16;15(4):517-28. Epub 2014 Dec 16.

Candiolo Cancer Institute-IRCCS, Laboratory of Medical Oncology, Experimental Cell Therapy , Candiolo, Turin , Italy.

Introduction: Conventional treatments reached an unsatisfactory therapeutic plateau in the treatment of advanced unresectable bone and soft tissue sarcomas that remain an unsolved medical need. Several evidences support the concept that adoptive immunotherapy may effectively integrate within the complex and multidisciplinary treatment of sarcomas.

Areas Covered: In this work we reviewed adoptive immunotherapy strategies that have been explored in sarcoma settings, with specific focus on issues related to their clinic transferability. We schematically divided approaches based on T lymphocytes specific for MHC-restricted tumor-associated antigens or relying on MHC-independent immune effectors such as natural killer (NK), cytokine-induced killer (CIK) or γδ T cells.

Expert Opinion: Preclinical findings and initial clinical reports showed the potentialities and drawbacks of different adoptive immunotherapy strategies. The expansion of tumor infiltrating lymphocytes is difficult to be reproduced outside melanoma. Genetically redirected T cells appear to be a promising option and initial reports are encouraging against patients with sarcomas. Adoptive immunotherapy with MHC-unrestricted effectors such as NK, CIK or γδ T cells has recently shown great preclinical potential in sarcoma setting and biologic features that may favor clinical transferability. Combination of different immunotherapy approaches and integration with conventional treatments appear to be key issues for successful designing of next clinical trials.
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http://dx.doi.org/10.1517/14712598.2015.987121DOI Listing
April 2015