Biology subjects

Munera-Maravilla, E.

Publications and source records attributed to Munera-Maravilla, E..

3 recordsLinked to original sources

bioRxiv2026

Circulating Immune Profiling Reveals Immune Signatures Associated with Disease Stage and Outcome in Endometrial Cancer

Although the tumor immune microenvironment has been studied in endometrial cancer, the systemic immune alterations associated with disease progression and their potential prognostic significance remain poorly defined. In this study, peripheral blood immune subsets were characterized by multiparametric flow cytometry in 67 patients with EC and 20 healthy controls, including dendritic cells, MDSCs, T-cell subsets, NK cells, and exhaustion and senescence associated markers. Immune profiles were similar between healthy controls and patients with early-stage disease, whereas advanced tumors showed marked changes, including dendritic cell expansion, reduced CD4+ T-cell proportions, and increased frequencies of CD8+CD27-CD28- and CD8+CD57+ populations. Among clinicopathologic features, MDSC levels were associated with tumor grade and myometrial infiltration, while regulatory T cells were increased in TP53-mutated and microsatellite-stable tumors. In the advanced cohort (n=31), non-responders frequently displayed elevated CD8+, CD8+CD27-CD28-, and CD8+CD57+ levels alongside decreased CD27+CD28+ proportions. In multivariable Cox models, higher baseline CD8+ (HR 1.13), CD8+ CD27-CD28- (HR 1.04), and CD8+CD57+ proportions (HR 1.07; all p<0.05) were independently associated with shorter PFS, whereas higher CD27+CD28+ levels were associated with improved PFS. CD27-CD28- proportions were also linked to worse PFS by Kaplan-Meier analysis (HR 5.1, log-rank p=0.005). Longitudinal analysis (n=28) showed that senescent-like lymphocyte levels remained associated with progression across timepoints (OR 18.80), whereas total CD8+ proportions diverged progressively, reaching significance only from 6 months onward. Together, these findings identify systemic immune remodeling as a characteristic of advanced endometrial cancer and support the potential of circulating immune profiling for patient stratification and prognostic assessment, pending validation in larger prospective cohorts.

cancer biology↗

bioRxiv2025

Cell-of-origin and genetic drivers define advanced bladder cancer subtypes and potential therapeutic response in mouse models

Bladder cancer (BC) remains a major clinical challenge owing to its high recurrence, limited treatment options, and molecular heterogeneity. Despite recent therapeutic advances, prognosis remains poor, and resistance is frequent, underscoring the need for improved experimental models to study tumorigenesis and therapeutic response. A key limitation of advanced BC research is the scarcity of in vivo models that accurately reflect invasive disease, with even fewer capturing the complexity of metastasis. To investigate how the cell-of-origin and specific combinations of driver mutations influence in bladder tumorigenesis, we developed and characterized four genetically engineered mouse models of advanced BC by targeting two combinations of tumor suppressor genes (Pten and Trp53, or Pten, Trp53, Rb1, and Rbl1) in basal or suprabasal urothelial cells through intravesical of Cre-adenovirus delivery. Loss of the retinoblastoma family reduced cancer-specific survival and was associated with more differentiated carcinomas. In both genetic backgrounds, luminal-derived tumors developed earlier but showed fewer metastatic events. Histopathological and transcriptomic analyses revealed that these tumors resemble human basal-squamous and stroma-rich subtypes, sharing regulatory networks and activated signaling pathways with human invasive tumors. Notably, tumors lacking retinoblastoma family genes exhibited increased immune infiltration, reinforcing the value of these models for diverse preclinical applications. To overcome detection and latency limitations, we established tumor-derived cell lines and generated syngeneic graft models. These were validated as preclinical platforms, exhibiting therapeutic responses to CDK4/6 inhibition and anti-PD-L1 immunotherapy. Our findings highlight the value of these novel models for studying BC progression and evaluating emerging therapeutic strategies in immunocompetent settings.

cancer biology↗

bioRxiv2023

Comprehensive Landscape of Non-muscle Invasive Bladder Cancer Tumour Microenvironment and Prognostic value of Cancer-Associated Myofibroblasts

BACKGROUNDNon-muscle-invasive bladder cancer (NMIBC) poses clinical challenges due to its high recurrence and progression rates. While Bacillus Calmette-Guerin (BCG) remains as the gold standard treatment for high-risk NMIBC, recent irruption of anti-PD-1/PD-L1 drugs claims for a comprehensive understanding of the tumour microenvironment (TME) of these tumors. METHODSThe present prospective study consisted on the analysis 98 fresh NMIBC samples, tumor and non-pathological tissue, via flow cytometry. Final analysis included distribution of 11 cell types and the expression of PD-L1 in 66 tumor and 62 non-pathological tissue biopsies from 73 NMIBC patients (84.4% paired samples). The results were validated using publicly available transcriptomic data, and histology. RESULTSIn comparison to non-pathological tissue, the TME of NMIBC presented microvascular alterations, increased cancer-associated fibroblast (CAF) and myofibroblast (myoCAF) presence, and varied immune cell distribution. Heterogeneous PD-L1 expression was observed across subsets, with cancer cells as primary potential anti-PD-L1 binding targets. Unbiased analysis revealed that myoCAF and M2-like macrophages are enriched in high grade NMIBC tumors, but only myoCAF were associated with higher rates of progression and recurrence, as we confirmed in three independent transcriptomic cohorts (888 total patients). We further validated the prognostic value of myoCAFs by tissue micro-array. CONCLUSIONThis comprehensive analysis provides a roadmap to establish the full landscape of the NMIB[C]s TME, highlighting myoCAFs as potential prognostic markers. FUNDINGThis study was funded by FC AECC (INVES222946GARC), Consejeria de Educacion, Ciencia y Universidades de la CAM (2018-T2/BMD-10342), Hoffmann-La Roche, Ministerio de Ciencia e Innovacion (INMUNOEPIBLA) and ISCIII/FEDER (CIBERONC CB16/12/00489)

cancer biology↗