Rodríguez, M.J. (María José)
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- The Toll like receptor 4 ligand cold-inducible RNA-binding protein as vaccination platform against cancer(Taylor & Francis, 2017) Silva, L. (Leyre); Rodríguez, M.J. (María José); Lozano-Moreda, T. (Teresa); Carrascosa, J.L. (José L.); Ruiz, M. (Marta); Hervas-Stubbs, S. (Sandra); Casares, N. (Noelia); Llopiz, D. (Diana); Sarobe, P. (Pablo); Iglesias-Alonso, T. (Tamara); Villanueva, L. (Lorea); Lasarte, J.J. (Juan José)Tumor infiltrating lymphocytes have been associated with a better prognostic and with higher response rates in patients treated with checkpoint inhibiting antibodies, suggesting that strategies promoting tumor inflammation may enhance the efficacy of these currently available therapies. Our aim was thus to develop a new vaccination platform based on cold-inducible RNA binding protein (CIRP), an endogenous TLR4 ligand generated during inflammatory processes, and characterize whether it was amenable to combination with checkpoint inhibitors. In vitro, CIRP induced dendritic cell activation, migration and enhanced presentation of CIRP-bound antigens to T-cells. Accordingly, antigen conjugation to CIRP conferred immunogenicity, dependent on immunostimulatory and antigen-targeting capacities of CIRP. When applied in a therapeutic setting, vaccination led to CD8-dependent tumor rejection in several tumor models. Moreover, immunogenicity of this vaccination platform was enhanced not only by combination with additional adjuvants, but also with antibodies blocking PD-1/PD-L1, CTLA-4 and IL-10, immunosuppressive molecules usually present in the tumor environment and also induced by the vaccine. Therefore, priming with a CIRP-based vaccine combined with immune checkpoint-inhibiting antibodies rejected established B16-OVA tumors. Finally, equivalent activation and T-cell stimulatory effects were observed when using CIRP in vitro with human cells, suggesting that CIRP-based vaccination strategies could be a valuable clinical tool to include in combinatorial immunotherapeutic strategies in cancer patients.
- How frequently benign uterine myomas appear suspicious for sarcoma as assessed by transvaginal ultrasound?(2023) Redondo, A. (Ana); Cabezas, N. (Nieves); Rodríguez, M.J. (María José); Díaz-de la Noval, B. (Begoña); Alcazar, J.L. (Juan Luis); Díaz, P. (Patricia); Guerriero, S. (Stefano); Lopez-Picazo, A. (Ana); Pascual, M.A. (Maria Angela); Ajossa, S. (Silvia); Valero, B. (Beatriz)Background: Uterine myomas may resemble uterine sarcomas in some cases. However, the rate of benign myomas appearing as sarcomas at an ultrasound examination is not known. The objective of this study is to determine the percentage of benign myomas that appear suspicious for uterine sarcoma on ultrasound examination. This is a prospective observational multicenter study (June 2019-December 2021) comprising a consecutive series of patients with histologically proven uterine myoma after hysterectomy or myomectomy who underwent transvaginal and/or transabdominal ultrasound prior to surgery. All ultrasound examinations were performed by expert examiners. MUSA criteria were used to describe the lesions (1). Suspicion of sarcoma was established when three or more sonographic features, described by Ludovisi et al. as frequently seen in uterine sarcoma, were present (2). These features are no visible myometrium, irregular cystic areas, non-uniform echogenicity, irregular contour, cooked appearance, and a Doppler color score of 3-4. In addition, the examiners had to classify the lesion as suspicious based on her/his impression, independent of the number of features present. Eight hundred and ten women were included. The median maximum diameter of the myomas was 58.7 mm (range: 10.0-263.0 mm). Three hundred and forty-nine (43.1%) of the patients had more than one myoma. Using the criterion of >3 suspicious features, 40 (4.9%) of the myomas had suspicious appearance. By subjective impression, the examiners considered 40 (4.9%) cases suspicious. The cases were not exactly the same. We conclude that approximately 5% of benign uterine myomas may exhibit sonographic suspicion of sarcoma. Although it is a small percentage, it is not negligible.
- Bendamustine as part of conditioning of autologous stem cell transplantation in patients with aggressive lymphoma: a phase 2 study from the GELTAMO group(2018) Gayoso, J. (Jorge); López-Guillermo, A. (Armando); Castro, N. (Nerea); Suárez-Lledó, M. (María); Briones, J. (Javier); Bello, J. I. (José I.); Rodríguez, M.J. (María José); López, A. (Andrés); Ramirez, M.J. (María Javier); Rifon, J. J. (Jose J.); Montes-Moreno, S. (Santiago); López-Jiménez, J. (Javier); Martin, A. (Alejandro); Caballero, D. (Dolores); Colorado, M. (Mercedes); Valcarcel, D. (David); Palomera, L. (Luis); Terol, M.J. (María José); Canales-Albendea, M. A. (Miguel Ángel); Sanchez, A. (Andrés); del Campo, R. (Raquel); Redondo, A. M. (Alba M.); Jarque, I. (Isidro); Arranz, R. (Reyes); González-Rodriguez, A.P. (Ana Pilar)We conducted a phase 2 trial to evaluate the safety and efficacy of bendamustine instead of BCNU (carmustine) in the BEAM (BCNU, etoposide, cytarabine and melphalan) regimen (BendaEAM) as conditioning for autologous stem-cell transplantation (ASCT) in patients with aggressive lymphomas. The primary endpoint was 3-year progression-free survival (PFS). Sixty patients (median age 55 [28–71] years) were included. All patients (except one who died early) engrafted after a median of 11 (9–72) and 14 (4–53) days to achieve neutrophil and platelet counts of >0.5 × 109/l and >20 × 109/l, respectively. Non-relapse mortality at 100 days and 1 year were 3.3% and 6.7%, respectively. With a median follow-up of 67 (40–77) months, the estimated 3-year PFS and overall survival (OS) were 58% and 75%, respectively. Patients in partial response at study entry had significantly worse PFS and OS than patients who underwent ASCT in complete metabolic remission, and this was the only prognostic factor associated with both PFS (Relative risk [RR], 0.27 [95% confidence interval {CI} [0.12–0.56]) and OS (RR, 0.40 [95% CI 0.17–0.97]) in the multivariate analysis. BendaEAM conditioning is therefore a feasible and effective regimen in patients with aggressive lymphomas. However, patients not in complete metabolic remission at the time of transplant had poorer survival and so should be considered for alternative treatment strategies.