Objective To identify a phenotype that could be informative and prognostic in patients with renal cell carcinoma (RCC) peripheral blood was evaluated for TH1, TH2, regulatory T cells (Tregs), natural killer (NK) and NKT cells and for cytokines/chemokines. Patients and Methods Peripheral blood from 77 patients with RCC and 40 healthy controls was evaluated by flow cytometry using monoclonal antibodies against CD4, CD25, FoxP3, CD45RA, CD45RO, CD152, CD184, CD279, CD3, CD16, CD56, CD161, CD158a, CD4, CD26, CD30, CD183 and CD184. A concomitant evaluation of 38 molecules was conducted in patients’ serum using a multiplex biometric ELISA‐based immunoassay. Results The number of NK cells CD3−/CD16+, CD3−/CD16+/CD161+ (NK) and CD3−/CD16+/CD161+/CD158a+ (NK‐ Kir 2+) was greater in the patients with RCC (P < 0.05); and the number of Treg cells CD4+/CD25high+/FOXP3+ and the subset CD4+/CD25high+/FOXP3+/CD45RA+ (naïve) and CD45R0+(memory) cells, were greater in the patients with RCC (P < 0.001). An increase in the following was observed in the serum of patients with RCC compared with healthy controls: interleukin (IL)‐4, IL‐6, IL‐8, IL‐10, G‐CSF, CXCL10, CXCL11, hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF). According to Ingenuity Pathway Analysis (IPA), CXCL10, IL‐6, IL‐8, epidermal growth factor (EGF), HGF and VEGF were associated with a network that controls cellular movement, tissue development and cellular growth. Kaplan–Meier analysis for disease‐free survival showed that high numbers of CD4+/CD25high+/FOXP3+/CD45RA+ (Treg naïve) and low numbers of CD3−/CD16+/CD161+/CD158a+ (NK‐Kir+) cells predict short disease‐free survival in patients with RCC. Conclusion Concomitant evaluation of Treg (CD4+/CD25high+/FOXP3+ and CD4+/CD25high+/FOXP3+/CD45RA+) and of six soluble factors (IL‐6, IL‐8 ,VEGF, CXCL10, CXCL11, EGF, HGF) might be a surrogate marker of host immunity in patients with RCC.

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Background Effects of immunosuppressive therapy (IST) on ventricular arrhythmias (VA) have not been reported in immune-mediated biopsy-proven myocarditis patients. Furthermore, myocarditis arrhythmic risk is still unpredictable. The aim of our study was to evaluate effectiveness of IST on VA in myocarditis patients, and stratify their arrhythmic risk, using clinical and diagnostic features, including serum organ-specific anti-heart (AHA) and antiintercalated-disk autoantibodies (AIDA). Methods From a cohort of 498 consecutive patients, we enrolled 255 cases with biopsy-proven virus-negative myocarditis and evidence of VA (VF, VT, NSVT, and Lown's grade ≥2 PVC) at index hospitalization. Serum AHA and AIDA were detected by a standardised indirect immunofluorescence technique. Whenever accepted and non-contraindicated, IST was started. Controls (IST-) were chosen after 1:1 matching to IST+ cases by age, gender, ethnicity, left ventricular ejection fraction, VA type, and treatment. Prospective follow-up (FU), occurred at defined timepoints. Results 58 matched patient couples (42±13 y, 67% males, 50% IST+) were analyzed in the main study cohort. Overall, 28 (24%) had VT, and 62 (53%) were discharged with ICD. IST duration was 12±1 months. No patients died and no serious complications from IST occurred. By 24-month FU, major VA occurred in 6 IST+ vs. 10 IST- patients (p=0.420), with no cases of VT following IST termination. As compared to IST- ones, IST+ patients showed a significant reduction in NSVT and PVC burden, as well as an improvement in clinical, laboratory and imaging findings (all p&lt;0.05). Major VA onset and positive AIDA status were independently associated with major VA at FU (HR 14.2, 95% CI 2.9–68.7, and 8.0, 95% CI 2.6–25.2, respectively, both p&lt;0.001). Furthermore, in the whole study population (N=255), IST played as an independent protective factor from major VA (HR 0.3, 95% CI 0.2–0.7, p=0.005) at 38±21 months FU. Conclusions In immune-mediated virus-negative myocarditis patients presenting with VA, IST is feasible and effective on NSVT and PVC burden, as well as on structural, laboratory and imaging endpoints. Short-term effects are limited on major VA, which were independently associated with major arrhythmic onset and positive AIDA, in keeping with the proposed etiopathogenetic involvement of autoimmunity in virus-negative myocarditis. Funding Acknowledgement Type of funding source: None

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