Gloria Peiró

Fetiform teratoma (FT) and fetus-in-fetu (FIF) represent a spectrum of rare retroperitoneal masses containing organoid structures. While FIF is classically defined by the presence of a vertebral axis, FT lacks this organized skeletal development. Distinguishing between these entities is critical given the malignant potential associated with FT, estimated at approximately 10%. We report a case of a 5-month-old male presenting with a large (12 cm) retroperitoneal mass and elevated alpha-fetoprotein (AFP 56.8 IU/mL; age-matched reference <7 IU/mL). Macroscopically, the resected tumor featured a distinct rudimentary digitiform projection with a nail bed. Histopathology demonstrated extensive organoid differentiation, including gastrointestinal loops with muscular layers, respiratory epithelium, and well-formed pancreatic parenchyma and adrenal cortex. Despite the complex organogenesis and limb-like morphology, the absence of a vertebral column or ossified long bones supported a diagnosis of mature cystic teratoma with fetiform features (FT) over FIF. This report highlights the diagnostic ambiguity within the “gray zone” of these lesions and emphasizes the role of axial skeletal organization and serum AFP levels as complementary tools for classification and oncologic surveillance.

Breast cancer (BC) is the most common cancer in women and the leading cause of cancer-related death worldwide. Systemic immune dysregulation is increasingly recognized as a critical component of BC pathophysiology. Therefore, the characterization of inflammatory mediators in this neoplasia has emerged as a focus of increasing research. In this study, we performed a multiplex analysis of 62 circulating immune-related molecules in serum samples from 229 BC patients prior to any treatment and 50 healthy controls. Serum samples were analyzed using the LEGENDplex™ protocol and measured by a spectral flow cytometer. Among the 62 circulating immune-related molecules initially analyzed, we identified a distinct serum signature comprising 27 soluble factors that significantly discriminated BC patients from healthy controls. The integration of these biomarkers into supervised machine learning models revealed that the Light Gradient Boosting Machine (LightGBM) algorithm achieved optimal diagnostic performance (AUC = 0.91; accuracy = 96.4%), with TSLP, IL-8, and IL-1β emerging as key predictive features. By integrating clinicopathological data, we identified significant associations between immune factor levels and tumor characteristics, including proliferation, lymph-node involvement, and histological grade. Stratification by molecular subtype also revealed distinct immunologic patterns. Significantly, elevated levels of IL-2RA and PD-1 were identified as promising candidates to predict shorter overall and disease-free survival, respectively. These findings provide novel insights into the systemic immune landscape of early-stage BC and support the use of circulating immune mediators as minimally invasive biomarkers for diagnosis and prognosis. However, external validation is needed to confirm the robustness and generalizability of these findings.

Breast cancer (BC) is the most common cancer in women and the leading cause of cancer-related death worldwide. This heterogeneous disease has been historically considered a non-immunogenic type of cancer. However, recent advances in immunotherapy have increased the interest in knowing the role of the immune checkpoints (IC) and other immune regulation pathways in this neoplasia. In this retrospective study, we evaluated the correlation of mRNA expression of CTLA-4, PDCD1 (PD1), CD274 (PD-L1), PDCD1LG2 (PD-L2), CD276 (B7-H3), JAK2, and FOXO1 with clinicopathological factors and BC patient’s outcome by real-time quantitative polymerase chain reaction (qPCR). Our results showed that immunoregulatory gene expression depends on BC immunophenotype being CTLA-4 and PDCD1 (PD1) overexpressed on triple-negative/basal-like (TN/BL) and luminal B/HER2-positive phenotypes, respectively, and CD276 (B7-H3), JAK2 and FOXO1 associated with both luminal A and luminal B/HER2-negative tumors. In addition, we found that these genes can also be related to aggressive and non-aggressive clinicopathological characteristics in BC. Finally, survival analysis showed that CTLA-4 expression levels emerge as a significant independent factor of good prognosis in BC patients, especially in the HER2-enriched subtype. Considering all these data, we can conclude that the expression of immunoregulatory genes depends on tumor phenotype and has potential clinical implications in BC patients.

Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) are the most frequently used rheumatoid arthritis (RA) diagnostic markers, but they are unable to anticipate the patient’s evolution or response to treatment. The aim of this study was to identify possible severity biomarkers to predict an upcoming flare-up or remission period. To address this objective, sera and anticoagulated blood samples were collected from healthy controls (HCs; n = 39) and from early RA (n = 10), flare-up (n = 5), and remission (n = 16) patients. We analyzed leukocyte phenotype markers, regulatory T cells, cell proliferation, and cytokine profiles. Flare-up patients showed increased percentages of cluster of differentiation (CD)3⁺CD4⁻ lymphocytes (p < 0.01) and granulocytes (p < 0.05) but a decreased natural killer (NK)/T lymphocyte ratio (p < 0.05). Analysis of leukocyte markers by principal component analysis (PCA) and receiver operating characteristic (ROC) curves showed that CD45RO⁺ (p < 0.0001) and CD45RA⁺ (p < 0.0001) B lymphocyte expression can discriminate between HCs and early RA patients, while CD3⁺CD4⁻ lymphocyte percentage (p < 0.0424) and CD45RA⁺ (p < 0.0424), CD62L⁺ (p < 0.0284), and CD11a⁺ (p < 0.0185) B lymphocyte expression can differentiate between flare-up and RA remission subjects. Thus, the combined study of these leukocyte surface markers could have potential as disease severity biomarkers for RA, whose fluctuations could be related to the development of the characteristic pro-inflammatory environment.

Advances in immunotherapy have increased interest in knowing the role of the immune system in breast cancer (BC) pathogenesis. Therefore, immune checkpoints (IC) and other pathways related to immune regulation, such as JAK2 and FoXO1, have emerged as potential targets for BC treatment. However, their intrinsic gene expression in vitro has not been extensively studied in this neoplasia. Thus, we evaluated the mRNA expression of tumor-cell-intrinsic CTLA-4, PDCD1 (PD1), CD274 (PD-L1), PDCD1LG2 (PD-L2), CD276 (B7-H3), JAK2, and FoXO1 in different BC cell lines, derived mammospheres, and co-cultures with peripheral blood mononuclear cells (PBMCs) by real-time quantitative polymerase chain reaction (qRT-PCR). Our results showed that intrinsic CTLA-4, CD274 (PD-L1), and PDCD1LG2 (PD-L2) were highly expressed in triple-negative cell lines, while CD276 was predominantly overexpressed in luminal cell lines. In contrast, JAK2 and FoXO1 were under-expressed. Moreover, high levels of CTLA-4, PDCD1 (PD1), CD274 (PD-L1), PDCD1LG2 (PD-L2), and JAK2 were found after mammosphere formation. Finally, the interaction between BC cell lines and peripheral blood mononuclear cells (PBMCs) stimulates the intrinsic expression of CTLA-4, PCDC1 (PD1), CD274 (PD-L1), and PDCD1LG2 (PD-L2). In conclusion, the intrinsic expression of immunoregulatory genes seems very dynamic, depending on BC phenotype, culture conditions, and tumor-immune cell interactions.

Absent in melanoma 2 (AIM2) is a cytosolic dsDNA sensor that has been broadly studied for its role in inflammasome assembly. However, little is known about the function of AIM2 in adaptive immune cells. The purpose of this study was to investigate whether AIM2 has a cell-intrinsic role in CD4⁺ T cell differentiation or function. We found that AIM2 is expressed in both human and mouse CD4⁺ T cells and that its expression is affected by T cell receptor (TCR) activation. Naïve CD4⁺ T cells from AIM2-deficient (Aim2^−/−) mice showed higher ability to maintain forkhead box P3 (FOXP3) expression in vitro, while their capacity to differentiate into T helper (Th)1, Th2 or Th17 cells remained unaltered. Transcriptional profiling by RNA sequencing showed that AIM2 might affect regulatory T cell (Treg) stability not by controlling the expression of Treg signature genes, but through the regulation of the cell’s metabolism. In addition, in a T cell transfer model of colitis, Aim2^−/−-naïve T cells induced less severe body weight loss and displayed a higher ability to differentiate into FOXP3⁺ cells in vivo. In conclusion, we show that AIM2 function is not confined to innate immune cells but is also important in CD4⁺ T cells. Our data identify AIM2 as a regulator of FOXP3⁺ Treg cell differentiation and as a potential intervention target for restoring T cell homeostasis.

Breast cancer is the leading cause of death among women worldwide. Over the years, oxidative stress has been linked to the onset and progression of cancer. In addition to the classical histological classification, breast carcinomas are classified into phenotypes according to hormone receptors (estrogen receptor—RE—/progesterone receptor—PR) and growth factor receptor (human epidermal growth factor receptor—HER2) expression. Luminal tumors (ER/PR-positive/HER2-negative) are present in older patients with a better outcome. However, patients with HER2-positive or triple-negative breast cancer (TNBC) (ER/PR/HER2-negative) subtypes still represent highly aggressive behavior, metastasis, poor prognosis, and drug resistance. Therefore, new alternative therapies have become an urgent clinical need. In recent years, anticancer agents based on natural products have been receiving huge interest. In particular, carotenoids are natural compounds present in fruits and vegetables, but algae, bacteria, and archaea also produce them. The antioxidant properties of carotenoids have been studied during the last years due to their potential in preventing and treating multiple diseases, including cancer. Although the effect of carotenoids on breast cancer during in vitro and in vivo studies is promising, clinical trials are still inconclusive. The haloarchaeal carotenoid bacterioruberin holds great promise to the future of biomedicine due to its particular structure, and antioxidant activity. However, much work remains to be performed to draw firm conclusions. This review summarizes the current knowledge on pre-clinical and clinical analysis on the use of carotenoids as chemopreventive and chemotherapeutic agents in breast cancer, highlighting the most recent results regarding the use of bacterioruberin from haloarchaea.

The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study, and 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1 mm portion of each lymph node was subjected to semi-serial sectioning at 200 μm intervals and examined by hematoxylin–eosin and immunohistochemistry with CK19; the remaining tissue was analyzed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/μL), the sensitivity of the OSNA assay was 92%, specificity was 82%, diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis.

Inhibitor of differentiation (ID) proteins are a family of transcription factors that contribute to maintaining proliferation during embryogenesis as they avoid cell differentiation. Afterward, their expression is mainly silenced, but their reactivation and contribution to tumor development have been suggested. In breast cancer (BC), the overexpression of ID1 has been previously described. However, whether the remaining ID genes have a specific role in this neoplasia is still unclear. We studied the mRNA expression of all ID genes by q RT-PCR in BC cell lines and 307 breast carcinomas, including all BC subtypes. Our results showed that ID genes are highly expressed in all cell lines tested. However, ID4 presented higher expression in BC cell lines compared to a healthy breast epithelium cell line. In accordance, ID1 and ID4 were predominantly overexpressed in Triple-Negative and HER2-enriched samples. Moreover, high levels of both genes were associated with larger tumor size, histological grade 3, necrosis and vascular invasion, and poorer patients’ outcomes. In conclusion, ID1 and ID4 may act as biomarkers of tumor aggressiveness and worse prognosis in breast cancer, and they could be used as potential targets for new treatments discover.