Browsing by Subject "MDSCs"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Publication
    Open Access
    Myeloid cell distribution and activity in multiple sclerosis
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Moliné-Velázquez, Verónica; Vila-del Sol, Virginia; de Castro, Fernando; Clemente, Diego
    Multiple sclerosis (MS) is a demyelinating disease in which an exacerbated immune response provokes oligodendrocyte loss and demyelination, the hallmarks of this neurological disease. The destruction of myelin due to the uncontrolled activity of the invading immune cells leads to the formation of MS plaques. Among the different leukocytes that participate in the immune response associated with MS, the role of myeloid cells has been analyzed extensively (i.e. macrophages, dendritic cells -DCs- and neutrophils). Hence, in this review we will summarize what is known about the distribution, expression and markers available to study myeloid cells, and their histopathology, not only in a standard animal model of MS (autoimmune experimental encephalomyelitis -EAE) but also in MS tissue. In this review, we will not only refer to mature myeloid cells but also to the undifferentiated and almost unexplored myeloid-derived suppressor cells (MDSCs). The active role of MDSCs in the prompt resolution of an immune episode is gaining importance, yet is still the subject of some debate. Finally, the similarities and differences between MS and EAE are discussed, particularly in terms of myeloid cell phenotype, activity and the markers used.
  • Thumbnail Image
    Publication
    Open Access
    Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015–04 (PANGEA-Breast) study
    (BioMed Central, 2022-12-03) Cruz-Merino, L. de la; Gion, M.; Cruz, J.; Alonso-Romero, José Luis; Quiroga, V.; Andrés, R.; Santisteban, M.; Ramos, M.; Holgado, E.; Cortés, J.; López-Miranda, E.; Cortés, A.; Henao, F.; Palazón-Carrión, N.; Rodriguez, L. M.; Ceballos, I.; Soto, A.; Puertes, A.; Casas, M.; Benito, S.; Chiesa, M.; Bezares, S.; Caballero, R.; Jiménez‑Cortegana, C.; Sánchez‑Margalet, V.; Rojo, F.; Medicina
    Background: We evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and the pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer (ABC) patients previously treated in the advanced setting, in order to explore a potential synergism that could eventually obtain long term benefit in these patients. Methods: HER2-negative ABC patients received 21-day cycles of pembrolizumab 200 mg (day 1) and gemcitabine (days 1 and 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) of gemcitabine (1,250 mg/m2 [DL0]; 1,000 mg/m2 [DL1]) to determine the recommended phase II dose (RP2D). The primary objective was objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloid-derived suppressor cells (MDSCs) levels in peripheral blood were analyzed. Results: Fourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the first stage of Simon’s design. Recruitment was stopped as statistical assumptions were not met. The median age was 52; 21 (58%) patients had triple-negative disease, 28 (78%) visceral involvement, and 27 (75%) ≥ 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5–32). Eight patients were treated ≥ 6 months before progression. Fourteen patients reported grade ≥ 3 treatment-related adverse events. Due to the small sample size, we did not find any clear association between immune tumor biomarkers and treatment efficacy that could identify a subgroup with higher probability of response or better survival. However, patients that experienced a clinical benefit showed decreased MDSCs levels in peripheral blood along the treatment. Conclusion: Pembrolizumab 200 mg and gemcitabine 1,250 mg/m2 were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for ≥ 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pretreated population, TILs, PD-L1 expression and MDSCs levels could not identify a subgroup of patients for whom the combination of gemcitabine and pembrolizumab would induce long term benefit of.
  • Thumbnail Image
    Publication
    Open Access
    Pembrolizumab plus gemcitabine in the subset of triple-negative advanced breast cancer patients in the GEICAM/2015-04 (PANGEA-Breast) study
    (MDPI, 2021-10-29) Cruz-Merino, Luis de la; Gion, María; Cruz-Jurado, Josefina; Quiroga, Vanesa; Andrés, Raquel; Moreno, Fernando; Alonso-Romero, José Luis; Ramos, Manuel; Holgado, Esther; Cortés, Javier; López-Miranda, Elena; Henao-Carrasco, Fernando; Palazón-Carrión, Natalia; Rodríguez, Luz M.; Ceballos, Isaac; Casas, Maribel; Benito, Sara; Chiesa, Massimo; Bezares, Susana; Caballero, Rosalia; Jiménez-Cortegana, Carlos; Sánchez-Margalet, Víctor; Rojo, Federico; Medicina
    The PANGEA-Breast trial evaluated a new chemo-immunotherapeutic combination that would synergistically induce long-term clinical benefit in HER2-negative advanced breast cancer patients. Treatment consisted of 21-day cycles of 200 mg of pembrolizumab (day 1) plus gemcitabine (days 1 and 8). The primary objective was the objective response rate (ORR). The tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumor, and the myeloid-derived suppressor cells (MDSCs) level in peripheral blood, were analyzed to explore associations with treatment efficacy. Considering a two-stage Simon’s design, the study recruitment was stopped after its first stage as statistical assumptions were not met. A subset of 21 triple-negative breast cancer (TNBC) patients was enrolled. Their median age was 49 years; 15 patients had visceral involvement, and 16 had ≤3 metastatic locations. Treatment discontinuation due to progressive disease (PD) was reported in 16 patients. ORR was 15% (95% CI 3.2–37.9). Four patients were on treatment >6 months before PD. Grade ≥3 treatment-related adverse events were observed in 8 patients, where neutropenia was the most common. No association was found between TILs density, PD-L1 expression or MDSCs levels and treatment efficacy. ORR in TNBC patients also did not meet the assumptions, but 20% were on treatment >6 months.