Immune cell labelling and tracking. implications for adoptive cell transfer therapies

BACKGROUND: The understanding of the role of different immune cell subsets that infiltrate tumors can help researchers in developing new targeted immunotherapies to reactivate or reprogram them against cancer. In addition to conventional drugs, new cell-based therapies, like adoptive cell transfer, proved to be successful in humans. Indeed, after the approval of anti-CD19 CAR-T cell therapy, researchers are trying to extend this approach to other cancer or cell types.MAIN BODY: This review focuses on the different approaches to non-invasively monitor the biodistribution, trafficking and fate of immune therapeutic cells, evaluating their efficacy at preclinical and clinical stages. PubMed and Scopus databases were searched for published articles on the imaging of cell tracking in humans and preclinical models.CONCLUSION: Labelling specific immune cell subtypes with specific radiopharmaceuticals, contrast agents or optical probes can elucidate new biological mechanisms or predict therapeutic outcome of adoptive cell transfer therapies. To date, no technique is considered the gold standard to image immune cells in adoptive cell transfer therapies

Role of [18F]FDG PET/CT in the management of G1 gastro-entero-pancreatic neuroendocrine tumors

Purpose: Since the role of [18F]FDG PET/CT in low-grade gastroenteropancreatic (GEP) neuroendocrine neoplasia (NET) is not well established, this study was aimed to evaluate the role of [18F]FDG PET/CT in grade 1 (G1) GEP-NETs. Methods: This is a retrospective study including patients with G1 GEP-NETs who underwent [18F]FDG PET/CT. Results: 55 patients were evaluated, including 24 (43.6%) with pancreatic NETs and 31 (56.4%) with gastrointestinal NETs. At the time of diagnosis, 28 (51%) patients had metastatic disease, and 50 (91%) patients were positive by 68-Ga sstr PET/CT. Overall, 27 patients (49%) had positive findings on [18F]FDG PET/CT. Following [18F]FDG PET/CT, therapeutic management was modified in 29 (52.7%) patients. Progression-free survival was longer in patients with negative [18F]FDG PET/CT compared with positive [18F]FDG PET/CT (median PFS was not reached and 24 months, respectively, p = 0.04). This significance was particularly evident in the pancreatic group (p = 0.008). Conclusions: Despite having low proliferative activity, approximately half of GEP-NETs G1 showed positive [18F]FDG PET/CT, with a corresponding negative impact on patients’ clinical outcomes. These data are in favor of a more “open” attitude toward the potential use of [18F]FDG PET/CT in the diagnostic work-up of G1 GEP-NETs, which may be used in selected cases to detect those at higher risk for an unfavorable disease course

Imaging activated-T-lymphocytes in the salivary glands of patients with sjögren’s syndrome by 99mTc-interleukin-2. diagnostic and therapeutic implications

Background: Sjögren’s syndrome (SS) is a progressive autoimmune disease characterized by local mononuclear cell infiltration of the salivary and lachrymal glands. Labial biopsy demonstrates local infiltration by Th1 cells that produce pro-inflammatory cytokines, such as interleukin-2 (IL2). The aim of this study was to assess the utility of 99mTc-labelled-IL2 (99mTc-IL2) in evaluating in vivo the extent and severity of lympho-mononuclear cell infiltration in the salivary glands of patients with SS. Methods: We investigated 48 patients with primary SS and 27 control subjects using 99mTc-IL2 scintigraphy. Furthermore, in a subgroup of 30 patients, we also performed 99mTc-pertechnetate scintigraphy (99mTcO4−) for evaluation of the salivary gland function. Results: 99mTc-IL2 uptake in the salivary glands of SS patients was higher than in the control subjects (1.30 ± 0.16 vs. 0.83 ± 0.08 for parotids and 1.36 ± 0.15 vs. 1.16 ± 0.07 for submandibular glands; p < 0.0001). The salivary gland uptake of 99mTc-IL2 in patients with a longer history of disease was lower compared with the recently diagnosed patients. A significant direct correlation was found between the uptake of 99mTc-IL2 and histology. Conclusions: 99mTc-IL2 scintigraphy showed that the degree of lymphocytic infiltration of major salivary glands is variable in patients with different disease durations. Patients with a high 99mTc-IL2 uptake could be efficiently treated with immuno-modulatory drugs and the efficacy of treatment could be followed-up by 99mTc-IL2 scintigraphy

Whole body MRI with diffusion weighted imaging versus 18F‑fuorodeoxyglucose‑PET/CT in the staging of lymphomas

Purpose To assess the diagnostic performance of Whole Body (WB)-MRI in comparison with 18F-Fluorodeoxyglucose-PET/CT (18F-FDG-PET/CT) in lymphoma staging and to assess whether quantitative metabolic parameters from 18F-FDG-PET/CT and Apparent Diffusion Coefficient (ADC) values are related. Materials and methods We prospectively enrolled patients with a histologically proven primary nodal lymphoma to undergo 18F-FDG-PET/CT and WB-MRI, both performed within 15 days one from the other, either before starting treatment (baseline) or during treatment (interim). Positive and negative predictive values of WB-MRI for the identification of nodal and extra-nodal disease were measured. The agreement between WB-MRI and 18F-FDG-PET/CT for the identification of lesions and staging was assessed through Cohen's coefficient k and observed agreement. Quantitative parameters of nodal lesions derived from 18F-FDG-PET/CT and WB-MRI (ADC) were measured and the Pearson or Spearman correlation coefficient was used to assess the correlation between them. The specified level of significance was p ≤ 0.05. Results Among the 91 identified patients, 8 refused to participate and 22 met exclusion criteria, thus images from 61 patients (37 men, mean age 30.7 years) were evaluated. The agreement between 18F-FDG-PET/CT and WB-MRI for the identification of nodal and extra-nodal lesions was 0.95 (95% CI 0.92 to 0.98) and 1.00 (95% CI NA), respectively; for staging it was 1.00 (95% CI NA). A strong negative correlation was found between ADCmean and SUVmean of nodal lesions in patients evaluated at baseline (Spearman coefficient rs = − 0.61, p = 0.001). Conclusion WB-MRI has a good diagnostic performance for staging of patients with lymphoma in comparison with 18F-FDG-PET/CT and is a promising technique for the quantitative assessment of disease burden in these patients

Upadacitinib effectiveness and factors associated with minimal disease activity achievement in patients with psoriatic arthritis: preliminary data of a real-life multicenter study

Background Upadacitinib (UPA) is a selective JAK inhibitor recently approved for the treatment of psoriatic arthritis (PsA). In this post-approval study, we aimed to evaluate the effectiveness and safety of UPA over 24 weeks and identify clinical predictors of response, in a multicentric cohort of patients affected by PsA.Methods One hundred and twenty-six patients with PsA treated with UPA were enrolled in 10 Italian centres. UPA effectiveness outcomes, such as the proportion of patients with MDA status, DAPSA remission, and low disease activity, ASDAS-CRP inactive and low disease activity, and change from baseline in DAPSA and ASDAS-CRP scores, were evaluated every 12 weeks until week 24. The proportion of DAPSA minor, moderate, and major improvement, and ASDAS clinically important improvement (CII) and major improvement (MI) were considered as well. All treatment-related adverse events were collected during the observation period. Clinical predictors of MDA response at week 24 were evaluated through multivariate analysis.Results At baseline, 124/126 (98%) and 54/126 (43%) patients showed peripheral and axial involvement, respectively; 110 (87%) patients were intolerant or resistant to biologic DMARDs.At 24 weeks, MDA status, DAPSA remission, and ASDAS-CRP inactive disease were achieved in 47%, 23%, and 48% of patients, respectively. Minor, moderate, and major DAPSA improvement was observed in 67%, 39%, and 23%, respectively; while 65% and 35% achieved ASDAS-CRP CII and MI, respectively. The mean change from baseline was 15.9 +/- 13.5 (p < 0.001) for DAPSA and 1.21 +/- 0.97 (p < 0.001) for ASDAS-CRP. thirteen patients (10%) discontinued UPA due to a lack of efficacy or non-serious adverse events. No serious adverse events were observed. Male gender (OR 2.54, 95% CI 1.03-6.25 p = 0.043), being naive to biological DMARDs (OR 4.13, 95% CI 1.34-12.71, p = 0.013) and elevated baseline CRP (OR 2.49, 95% CI 1.02-6.12, p = 0.046) were associated with MDA response at week 24.conclusions this is one of the first real-life studies supporting the effectiveness of UPA and its safety profile in PsA patients. Furthermore, the study identifies predictors of MDA response to UPA treatment at 6 months

Closing address [by Paolo Gentiloni, Prime Minister of Italy]

This contribution was delivered on the occasion of the EUI State of the Union in Florence on 5 May 2017This intervention was part of the recorded SoU afternoon session that took place on 5 May 2017 available on Youtube; move to the part of the video session of your interest within the video recording

Social Changes and Political Sistem in Italy

Italy's long 1960s between the word miracle and the political and social chang

La fine della guerra fredda. Prospettive e punti di vista

Dopo 30 anni dal 1989 riflessioni e giudizi di studiosi di diversi paesi sul significato di una data periodizzante, tra cesure e continuità. Il peso del confronto storiografico nella sua evoluzione più recente