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Introduction: In the current study, we have investigated the effects of the different modalities of treatment (volume of radiotherapy [RT], previous surgery) as well as the Gleason score of prostate cancer (PC) on the lymphocyte composition of PC patients undergoing RT., Methods: This is a monoinstitutional study that prospectively included PC patients that underwent RT from January 2016 until December 2017. To compare the different evaluations, the Wilcoxon signed-rank test was used among 2 times (Timepoint 0 to Timepoint 1). Percentage variation was calculated for all the lymphocyte subpopulation and was correlated with clinical parameters (previous surgery, Gleason score, and pelvic irradiation) with the χ2 test. The statistical analysis was repeated also on the stratified dataset according to the above parameters (previous surgery, Gleason score, and whole pelvic radiotherapy [WPRT])., Results: One hundred and eleven patients were included in the present analysis. All the lymphocyte subpopulations resulted significantly lower after RT. The modifications of several lymphocyte subpopulations correlated with previous surgery, Gleason score, and WPRT, although stratified analysis demonstrated that WPRT showed the greatest correlation., Conclusion: Our results could be used to design a prospective trial in order to study the use of WPRT on the lymphocyte subpopulations., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Olaparib is effective in metastatic triple negative breast cancer (TNBC) carrying germline mutations in DNA damage repair (DDR) genes BRCA1/2 (g BRCA -mut). The OLTRE window-of-opportunity trial preliminarily investigated potential pathologic, radiometabolic and immune biomarkers of early-response to olaparib in g BRCA -wild-type (wt) TNBC and, as proof-of-concept in g BRCA -mut HER2-negative BC., Methods: Patients received olaparib for 3 weeks (3w) before standard neoadjuvant chemotherapy and underwent multiple FDG 18 -PET/CT scan (basal, after olaparib), clinical assessments (basal, every 3w), tumor biopsies and blood samplings (baseline, after olaparib). Clinical and radiometabolic responses were evaluated according to RECIST1.1 and PERCIST criteria., Results: 27 patients with g BRCA -wt TNBC and 8 with g BRCA -mut BC (6 TNBC, 2 HR+/HER2-negative) were enrolled. Three (11.1%) patients showed mutations in non- BRCA 1/2 DDR genes and 4 (14.8%) in other genes. 3w olaparib induced 16/35 and 15/27 partial clinical and radiometabolic responses, including in 40.7% and 50.0% g BRCA -wt patients. g BRCA -mut tumors presented numerically higher tumor-infiltrating lymphocytes (TILs) levels and PD-L1 positive tumors. Clinical responders experienced a reduction in T-regs/T-eff ratio (p=0.05), B and NK lymphocytes (p=0.003 both), with an average increase in T-helpers rate (p<0.001) and CD4/CD8 ratio (p=0.02). Ki67% and TILs did not vary significantly (p=0.67 and p=0.77). A numerical increase in PD-L1 positive cases after olaparib was observed, though non-significant (p=0.134). No differences were observed according to g BRCA status and type of response., Conclusions: Early-stage TNBC might be a target population for olaparib, irrespective of g BRCA mutations. Future trials should combine TILs, PD-L1 and g BRCA status to better identify candidates for escalated/de-escalated treatment strategies including olaparib., Competing Interests: EM, AB, LX, EZ and DC were employed by Personal Genomics Ltd. GW and ML are employed at Oncologica UK Ltd., which has received project funding from AstraZeneca outside of the submitted work. DG has declared consulting fees from Novartis, Lilly and Pfizer, research funding from LILT, Novartis, Astra-Zeneca and University of Trieste outside of the submitted work. IP has declared consulting fees from Roche, Novartis, Lilly, Pfizer, Astra-Zeneca, Pierre Fabre and Ipsen outside of the submitted work. GS has declared Grant/Research Support from MSD Italia S.r.l., consulting role for TESARO Bio Italy S.r.l. Johnson & Johnson and Clovis Oncology Italy S.r.l., outside of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schettini, Corona, Giudici, Strina, Sirico, Bernocchi, Milani, Ziglioli, Aguggini, Azzini, Barbieri, Cervoni, Cappelletti, Molteni, Lazzari, Ferrero, Ungari, Marasco, Bruson, Xumerle, Zago, Cerra, Loddo, Williams, Paris, Scambia and Generali.)

Purpose: mTOR inhibitor everolimus is used for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (mBC). No reliable predictive biomarker of response is available. Following evidences from other solid tumors, we aimed to assess the association between treatment-associated immune system features and everolimus activity., Methods: We retrospectively explored a correlation with the therapeutic activity of everolimus and tumor-associated immune pathways with ingenuity pathway analysis (IPA), neutrophil-to-lymphocyte ratio (NLR), circulating lymphocytes, and endothelial cells (CECs) in 3 different HR+ mBC studies, including the BALLET phase IIIb study., Results: The circulating levels of CD3 + /CD8 + , CD3 + /CD4 + , and overall T lymphocytes were higher in responders versus non-responders at baseline (p = 0.017, p < 0.001, p = 0.034) and after treatment (p = 0.01, p = 0.003, p = 0.023). Reduced CECs, a tumor neoangiogenesis marker, were observed in responders after treatment (p < 0.001). Patients with low NLR (≤ 4.4) showed a better progression-free survival compared to patients with high NLR (> 4.4) (p = 0.01). IPA showed that the majority of immunity-related genes were found upregulated in responders compared to non-responders before treatment, but not after., Conclusions: Lymphocytes subpopulations, CECs and NLR could be interesting biomarkers predictive of response to everolimus-based regimens, potentially useful in daily clinical practice to select/monitor everolimus-based treatment in mBC. Further studies to confirm such hypotheses are warranted.

Background: The expression of the immunoglobulin superfamily cell membrane adhesion molecule CD146 has been reported on several normal and pathological cell types in human. The aim of this study was to investigate CD146 expression in acute leukemia using a multiparametric cytofluorimetric approach., Methods: Cytofluorimetric and cytogenetic studies were performed on peripheral blood and bone marrow samples from 162 patients with acute myeloid leukemia (AML, n = 121) and acute lymphoblastic leukemia (ALL, n = 41). ALL patients were subdivided in B-ALL (n = 38) and T-ALL (n = 3). Adult (n = 18) and pediatric (n = 20) B-ALL were considered as a whole group., Results: Four out of 121 (3.3%) AML cases, 14/38 (36.8%) B-ALL, and 2/3 (66.6%) T-ALL expressed CD146 on 12-98% of blasts (p < 0.001). CD146 expression was not observed in 10 healthy controls. Among B-ALL CD146-positive cases, 78.6% were associated with a "common"/BII-ALL and 21.4% with a pre-B/BIII-ALL immunophenotype while pro-B/BI-ALL and mature-B/BIV-ALL cases were CD146-negative. Statistical analysis showed CD146 expression strongly associated with Ph+ positivity in B-ALL with the highest percentage of CD146-positive blasts in all Ph-positive B-ALL cases (84 ± 22% Ph-positive B-ALL SD vs. 40 ± 24% SD in Ph-negative B-ALL; p < 0,001)., Conclusion: In our series, CD146 was expressed in all cases of Ph-positive B-ALL and in the vast majority of T-ALL, whereas it was rarely expressed by AML blasts. We suggest that CD146 may be considered as an additional marker for acute lymphoblastic leukemia diagnosis and monitoring of minimal residual disease in those cases which are CD146-positive at diagnosis. © 2015 International Clinical Cytometry Society., (© 2015 International Clinical Cytometry Society.)