Follicle-intrinsic and spatially distinct molecular programs drive follicle rupture and luteinization during ex vivo mammalian ovulation.

During ovulation, the apical wall of the preovulatory follicle breaks down to facilitate gamete release. In parallel, the residual follicle wall differentiates into a progesterone-producing corpus luteum. Disruption of ovulation, whether through contraceptive intervention or infertility, has implications for women's health. In this study, we harness the power of an ex vivo ovulation model and machine-learning guided microdissection to identify differences between the ruptured and unruptured sides of the follicle wall. We demonstrate that the unruptured side exhibits clear markers of luteinization after ovulation while the ruptured side exhibits cell death signals. RNA-sequencing of individual follicle sides reveals 2099 differentially expressed genes (DEGs) between follicle sides without ovulation induction, and 1673 DEGs 12 h after induction of ovulation. Our model validates molecular patterns consistent with known ovulation biology even though this process occurs in the absence of the ovarian stroma, vasculature, and immune cells. We further identify previously unappreciated pathways including amino acid transport and Jag-Notch signaling on the ruptured side and glycolysis, metal ion processing, and IL-11 signaling on the unruptured side of the follicle. This study yields key insights into follicle-inherent, spatially-defined pathways that underlie follicle rupture, which may further understanding of ovulation physiology and advance women's health.

TP53 mutations and survival in ovarian carcinoma patients receiving first-line chemotherapy plus bevacizumab: Results of the MITO16A/MaNGO OV-2 study.

To date, there are no biomarkers that define a patient subpopulation responsive to bevacizumab (BEV), an effective treatment option for advanced ovarian carcinoma (OC). In the context of the MITO16A/MaNGO OV-2 trial, a Phase IV study of chemotherapy combined with BEV in first-line treatment of advanced OC, we evaluated TP53 mutations by next-generation sequencing and p53 expression by immunohistochemistry (IHC) on 202 and 311 cases, respectively. We further correlated TP53 mutations in terms of type, function, and site, and IHC data with patients' clinicopathological characteristics and survival. TP53 missense mutations of unknown function (named unclassified) represented the majority of variants in our population (44.4%) and were associated with a significantly improved overall survival (OS) both in univariable (hazard ratio [HR] = 0.43, 95% confidence interval [CI] = 0.20-0.92, p = .03) and multivariable analysis (HR = 0.39, 95% CI = 0.18-0.86, p = .02). Concordance between TP53 mutational analysis and IHC was 91%. We observed an HR of 0.70 for OS in patients with p53 IHC overexpression compared to p53 wild-type, which however did not reach statistical significance (p = .31, 95% CI = 0.36-1.38). Our results indicate that the presence of unclassified TP53 mutations has favorable prognostic significance in patients with OC receiving upfront BEV plus chemotherapy. In particular, unclassified missense TP53 mutations characterize a subpopulation of patients with a significant survival advantage, independently of clinicopathological characteristics. Our findings warrant future investigations to confirm the prognostic impact of TP53 mutations in BEV-treated OC patients and deserve to be assessed for their potential predictive role in future randomized clinical studies.

Machine learning-based discrimination of benign and malignant breast lesions on US: The contribution of shear-wave elastography.

PURPOSE: To build and validate a combined radiomics and machine learning (ML) approach using B-mode US and SWE images to differentiate benign from malignant solid breast lesions (BLs) and compare its performance with that of an expert radiologist. METHODS: Patients with at least one BI-RADS 2-6 BL who performed breast US integrated with SWE were retrospectively included. B-mode US and SWE images were manually segmented to extract radiomics features. A multi-step feature selection process was performed and a predictive model built using the Logistic Regression algorithm. The diagnostic accuracy was evaluated with the AUC and Matthews Correlation Coefficient (MCC) metrics. The performance of the ML classifier was compared to that of an expert radiologist. RESULTS: 427 Bls were included and divided into a training (286 BLs, of which 127 benign and 159 malignant) and a test set (141 BLs, of which 59 benign and 82 malignant). Of 1098 features extracted from B-mode US and SWE images, 13 were finally selected. The ML classifier showed an AUC of 0.768 and 0.746, and an MCC of 0.403 and 0.423 in the training and test sets, respectively. The performance was higher than that of the expert radiologist assessing only B-mode US images, but significantly lower when SWE images were also provided. CONCLUSION: A ML approach based on B-mode US and SWE images may represent a potential tool in the characterization of BLs. SWE still gives its most relevant contribution in the clinical setting rather than included in a radiomics pipeline.

Humulus lupulus L.: Evaluation of Phytochemical Profile and Activation of Bitter Taste Receptors to Regulate Appetite and Satiety in Intestinal Secretin Tumor Cell Line (STC-1 Cells).

SCOPE: Inflorescences of the female hop plant (Humulus lupulus L.) contain biologically active compounds, most of which have a bitter taste. Given the rising global obesity rates, there is much increasing interest in bitter taste receptors (TAS2Rs). Intestinal TAS2Rs can have beneficial effects on obesity when activated by bitter agonists. This study aims to investigate the mechanism of action of a hydroalcoholic hop extract in promoting hormone secretion that reduces the sense of hunger at the intestinal level through the interaction with TAS2Rs. METHODS AND RESULTS: The results demonstrate that the hop extract is a rich source of bitter compounds (mainly α-, ß-acids) that stimulate the secretion of anorexigenic peptides (glucagon-like peptide 1 [GLP-1], cholecystokinin [CCK]) in a calcium-dependent manner while reducing levels of hunger-related hormones like ghrelin. This effect is mediated through interaction with TAS2Rs, particularly Tas2r138 and Tas2r120, and through the activation of downstream signaling cascades. Knockdown of these receptors using siRNA transfection and inhibition of Trpm5, Plcß-2, and other calcium channels significantly reduces the hop-induced calcium response as well as GLP-1 and CCK secretion. CONCLUSIONS: This study provides a potential application of H. lupulus extract for the formulation of food supplements with satiating activity capable of preventing or combating obesity.

Airway Clearance Techniques in Primary Ciliary Dyskinesia: A Systematic Review.

OBJECTIVE: Primary ciliary dyskinesia (PCD) is a respiratory disorder that impairs mucociliary clearance, leading to decreased lung function. Conventional chest physiotherapy (CCP) is the traditional airway clearance technique (ACT) and is considered a standard treatment for PCD patients. This systematic review investigated whether device supported ACTs are better alternatives for improving lung function and/or quality of life in PCD, compared with CCP. METHODS: The OVID Medline, PubMed, CINAHL, and Cochrane databases were searched. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and the Grading of Recommendations, Assessment, Development, and Evaluation approach was used to aggregate the data. This systematic review has been registered on the International Prospective Register of Systematic Reviews website. RESULTS: Of the 389 citations that resulted from our literature search, 2 randomized crossover trials that included a total of 54 patients were analyzed. The certainty of the aggregated study evidence was very low. No difference was identified between device-supported ACTs and CCP in terms of forced vital capacity and forced expiratory volume in 1 second in PCD patients aged 6 to 20 years. CONCLUSION: Device-supported ACTs could be considered alternative treatment options to replace CCP. High quality research is required to confirm this result.

Extraction Optimization of Quercus cerris L. Wood Chips: A Comparative Study between Full Factorial Design (FFD) and Artificial Neural Network (ANN).

From a circular bio-economy perspective, biomass valorization requires the implementation of increasingly efficient extraction techniques to ensure the environmental and economic sustainability of biorefining processes. This research focuses on optimizing the specialized metabolite extraction of Turkey oak chips from Quercus cerris L. by applying a 3 levels Full Factorial Design (FFD). The goal is to obtain an extract with the highest antioxidant activity [evaluated by 1,1-diphenyl-2-picryl hydrazyl (DPPH) scavenging activity and ferric reducing antioxidant power (FRAP) assays] and specialized metabolites content [measured as total phenolic content (TPC), total flavonoid content (TFC), condensed tannin content (CTC), and hydrolysable tannins content (THC)]. With this objective, three different variables were investigated and compared: temperature (20 °C, 50 °C, 80 °C), solvents EtOH/H2O (0%, 20%, 40%), and time (3 h, 6 h, 24 h), resulting in 27 different extracts. Following the FFD analysis, the optimal extractive conditions were determined to be 80 °C, 40% EtOH/H2O, and 19.8 h. Finally, the prediction ability of FFD was compared with that of artificial neural network (ANN) for DPPH scavenging activity, FRAP, and TPC data based on the coefficient of determination (R2), mean absolute error (MAE), and root mean square error (RMSE). The results indicated that ANN predictions were more precise than FFD ones; however, both methods were useful in optimizing the extraction process as they returned comparable optimized extraction parameters.

Dermatofibrosarcoma protuberans of the breast: A rare breast tumor mimicking a cutaneous lesion.

INTRODUCTION AND IMPORTANCE: Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue tumor which generally affects people from the second to the fifth decades of life, with the same incidence in both sexes. DFSP can appear as a slow-growing, flesh-colored or erythematous plaque or nodule, often becoming protuberant if untreated. CASE PRESENTATION: We report two cases of DFSP. The first case regards a 22-year-old woman with a 1.5-centimeter, mobile nodule of hard-elastic consistency in the left breast initially suspected to be a sebaceous cyst. Ultrasound and MRI suggested benign features, but histopathological examination post-excision confirmed DFSP. The second patient come to our attention is a 54-year-old woman with a 6 mm erythematous lump in the right breast, which reached 22 mm after two years. Mammography and histological examination post-excision confirmed DFSP. Both patients underwent to wide local excision and after four years of follow-up no recurrence or complications are observed. CLINICAL DISCUSSION: DFSP is a soft tissue sarcoma with low metastatic potential but requires early diagnosis and surgical excision to avoid malignant transformation. There are no standardized guidelines for its diagnosis and treatment. Imaging techniques, including ultrasound, CT, and MRI, are crucial to define tumor extension and planning surgical intervention. Surgical excision with clear margins is the primary treatment, but there are also emerging treatments as Mohs micrographic surgery or Imatinib Mesylate therapy for unresectable cases. CONCLUSION: Our cases highlight the importance of an accurate diagnostic evaluation and effective surgical management to achieve favorable outcomes.

Nutraceutical Valorization of Exhausted Olive Pomace from Olea europaea L. Using Advanced Extraction Techniques.

Exhausted olive pomace (EOP) represents the principal residue of olive pomace. Several studies have optimized the extraction of specialized metabolites from the EOP of Olea europaea L., but a comparison between different extractive methods has not been made. For this reason, the present investigation aims to compare four different extractive methods by using water and 15% ethanol/water as extractive solvents. Specifically, based on extract antioxidant activity, the methods compared were maceration (MAC), microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), and Accelerated Solvent Extraction (ASE). Between these, the UAE and ASE hydroalcoholic EOP extracts were demonstrated to have the highest antioxidant activity. Subsequently, these extracts were investigated for their hypoglycemic and antiradical activity using in vitro cell-free and cell-based assays, respectively. ASE hydroalcoholic EOP extract demonstrated the greatest ability to inhibit the α-amylase enzyme and an in vitro antioxidant activity comparable to N-acetyl cysteine in HepG2 cells. UAE and ASE extracts' phytochemical characterization was also performed, identifying seven phenolic compounds, including 3-hydroxytyrosol, tyrosol, and, for the first time, salidroside. The ASE hydroalcoholic EOP extract was the richest from a phytochemical point of view, thus confirming its major biological activity. Therefore, ASE and 15% ethanol/water may represent the best extractive method for EOP nutraceutical valorization.

Missed opportunities in the prevention and diagnosis of pediatric tuberculosis: a scoping review

Abstract Objectives: Identify potential barriers, delays, and missed opportunities in the prevention and diagnosis of childhood TB. Methods: Scoping review according to the PRISMA extension. The definitions considered for the selection followed the acronym PCC where the population (P) is children under 18years of age with TB disease, the concept (C) refers to missed opportunities for prevention and diagnosis, and context (C) is defined as a diagnosis of TB disease. The authors searched systematically in the databases; VHL/Lilacs, Medline via PubMed, Cochrane, Scopus, and Web of Science, without date or language limitation. Results: Seven studies were included. In developed countries, with low disease burden, the main shortcoming is the delay in diagnosing bacilliferous adults in contact with young children. This problem is concentrated in the portion of the population with socioeconomic vulnerability. In underdeveloped countries, with a high burden of disease, the biggest challenge is tracking children who come into contact with bacilliferous patients. Conclusions: There are still many missed opportunities in the prevention and diagnosis of childhood TB. The positive legacy of the COVID-19 pandemic should be taken advantage of and the encouragement of scientific development in the management of infectious diseases should be taken.

Single-cell and spatiotemporal profile of ovulation in the mouse ovary.

Ovulation is a spatiotemporally coordinated process that involves several tightly controlled events, including oocyte meiotic maturation, cumulus expansion, follicle wall rupture and repair, and ovarian stroma remodeling. To date, no studies have detailed the precise window of ovulation at single-cell resolution. Here, we performed parallel single-cell RNA-seq and spatial transcriptomics on paired mouse ovaries across an ovulation time course to map the spatiotemporal profile of ovarian cell types. We show that major ovarian cell types exhibit time-dependent transcriptional states enriched for distinct functions and have specific localization profiles within the ovary. We also identified gene markers for ovulation-dependent cell states and validated these using orthogonal methods. Finally, we performed cell-cell interaction analyses to identify ligand-receptor pairs that may drive ovulation, revealing previously unappreciated interactions. Taken together, our data provides a rich and comprehensive resource of murine ovulation that can be mined for discovery by the scientific community.

Guardians and Mediators of Metastasis: Exploring T Lymphocytes, Myeloid-Derived Suppressor Cells, and Tumor-Associated Macrophages in the Breast Cancer Microenvironment.

Breast cancers (BCs) are solid tumors composed of heterogeneous tissues consisting of cancer cells and an ever-changing tumor microenvironment (TME). The TME includes, among other non-cancer cell types, immune cells influencing the immune context of cancer tissues. In particular, the cross talk of immune cells and their interactions with cancer cells dramatically influence BC dissemination, immunoediting, and the outcomes of cancer therapies. Tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs) represent prominent immune cell populations of breast TMEs, and they have important roles in cancer immunoescape and dissemination. Therefore, in this article we review the features of TILs, TAMs, and MDSCs in BCs. Moreover, we highlight the mechanisms by which these immune cells remodel the immune TME and lead to breast cancer metastasis.

Investigation of the structure of protein-polymer conjugates in solution reveals the impact of protein deuteration and the size of the polymer on its thermal stability.

The conjugation of proteins with polymers offers immense biotechnological potential by creating novel macromolecules. This article presents experimental findings on the structural properties of maltose-binding protein (MBP) conjugated with linear biodegradable polyphosphoester polymers with different molecular weights. We studied isotopic effects on both proteins and polymers. Circular dichroism and fluorescence spectroscopy and small-angle neutron scattering reveal that the conjugation process destabilizes the protein, affecting the secondary more than the tertiary structure, even at room temperature, and that the presence of two domains in the MBP may contribute to its observed instability. Notably, unfolding temperatures differ between native MBP and the conjugates. In particular, this study sheds light on the complex interplay of factors such as the deuteration influencing protein stability and conformational changes in the conjugation processes. The perdeuteration influences the hydrogen bond network and hydrophobic interactions in the case of the MBP protein. The perdeuteration of the protein influences the hydrogen bond network and hydrophobic interactions. This is evident in the decreased thermal stability of deuterated MBP protein, in the conjugate, especially with high-molecular-mass polymers.

Harmonization of homologous recombination deficiency testing in ovarian cancer: Results from the MITO16A/MaNGO-OV2 trial.

BACKGROUND: Homologous Recombination Deficiency (HRD) status predicts response to treatment with poly(ADP-ribose) polymerase inhibitors in Ovarian Cancer (OC) patients. The Myriad myChoiceCDx Assay is approved by Food and Drug Agency for the HRD assessment. Here we compared the HRD status obtained by three commercial panels with the results from Myriad reference test. METHODS: The HRD analysis was performed on DNA from formalin-fixed and paraffin-embedded tumor samples of 100 untreated OC patients for which Myriad assay results were available, using TruSight Oncology 500 HRD assay (Illumina), Oncomine Comprehensive Assay Plus (Thermo Fisher Scientific) and SOPHiA DDM HRD solution panel (SOPHiA Genetics). RESULTS: A good overall concordance with the reference method was demonstrated at three different levels: BRCA mutational status (from 94.4 % to 97.7 %), the genomic instability value (from 88.2 % to 95.3 %) and for the HRD status (from 90.4 % to 97.6 %). Moreover, a trend in favour of HRD positive patients for response rate, progression-free survival and overall survival similar to Myriad was observed for all three tests. DISCUSSION: Our data suggest the feasibility of commercial testing for assessing HRD status, with a good concordance with the reference method and association with clinical outcome.

Malus pumila Mill. cv Annurca apple extract might be therapeutically useful against oxidative stress and patterned hair loss.

Patterned hair loss (PHL) or androgenetic alopecia is a condition affecting about 50% of people worldwide. Several pharmacological medications have been developed over the years, but few studies have investigated their effectiveness. Therefore, new, safer and more effective strategies are required. Recent investigations showed that Annurca apple extract application could induce keratin production and promote hair growth thanks to the high amount of procyanidin B2 contained in. Hence, this study aimed to investigate the role of an Annurca apple extract in preventing PHL by testing it on human follicle dermal papilla cells (HFDPCs) for the first time. Treatment of HFDPCs with Annurca apple extract counteracted intracellular reactive oxygen species accumulation by increasing the activity of antioxidant enzymes such as superoxide dismutase 2 and catalase. Furthermore, treatment with Annurca apple extract increased ß-catenin and fibroblast growth factor 2, which are involved in hair growth stimulation. These data suggest that Annurca apple extract may be a potential therapeutically useful nutraceutical product for preventing or treating hair loss by reducing oxidative stress and inducing the expression of hair growth-related factors.

Case report: EBV-related eye orbits and sinuses lymphohistiocytic infiltration responsive to rituximab in a patient with X lymphoproliferative syndrome type 1.

Background and aims: X lymphoproliferative syndrome type 1 (XLP1) is a rare inborn error of immunity due to mutations of SH2D1A, encoding for slam-associated protein (SAP). The clinical phenotype includes severe mononucleosis, hemophagocytic lymphohistiocytosis (HLH), and B-cell lymphomas. Methods: We report the case of a child affected with XLP1 who presented with an incomplete HLH, triggered by Epstein-Barr virus (EBV) and treated with rituximab, involving orbits and paranasal sinuses. Results: The lesion was indistinguishable from lymphoma, complicating diagnosis and treatment. In addition, considering the high incidence of lymphoma in patients with XLP1, histology helped define its nature, driving therapeutic choices. Conclusion: We described an unusual presentation of incomplete HLH in a patient affected with XLP1: an EBV-driven infiltration of the orbits and paranasal sinuses. This led us to a challenging differential diagnosis of lymphoma-associated hemophagocytic syndrome, which can be frequently observed in patients with XLP1. Considering the extremely poor prognosis of this clinical finding, we sought for a prompt diagnosis and managed to obtain it and to immediately establish the right treatment on the basis of the pathological finding.

Wastewater irrigation and Trichoderma colonization in tomato plants: effects on plant traits, antioxidant activity, and performance of the insect pest Macrosiphum euphorbiae.

The scarcity of freshwater for agriculture in many regions has led to the application of sewage and saline water for irrigation. Irrigation with non-conventional water sources could become a non-harmful process for plant cultivation, and the effects of their use on crops should be monitored in order to develop optimal management strategies. One possibility to overcome potential barriers is to use biostimulants such as Trichoderma spp. fungi. Tomato is a crop of great economic importance in the world. This study investigated the joint effects of Trichoderma afroharzianum T-22 on tomato plants irrigated with simulated unconventional waters. The experiment consisted of a control and three water treatments. In the control, the plants were watered with distilled water. The three water treatments were obtained by using an irrigation water added with nitrogen, a wastewater effluent, and a mixed groundwater-wastewater effluents. Potted tomato plants (variety Bobcat) were grown in a controlled growth chamber. Antioxidant activity, susceptibility to the aphids Macrosiphum euphorbiae, and tomato plant growth parameters were estimated. Trichoderma afroharzianum T-22 had a positive effect on plant growth and antioxidant defenses when plants were irrigated with distilled water. Instead, no significant morphological effects induced by T. afroharzianum T-22 on plants were observed when unconventional water was used for irrigation. However, inoculation with T. afroharzianum T-22 activated a stress response that made the colonized plants more susceptible to aphid development and increased their fecundity and longevity. Thanks to this study, it may be possible for the first time to open a new discussion on the practical possibility of using reclaimed wastewater for crop irrigation with the addition of a growth-promoting fungal symbiont.

Missed opportunities in the prevention and diagnosis of pediatric tuberculosis: a scoping review.

OBJECTIVES: Identify potential barriers, delays, and missed opportunities in the prevention and diagnosis of childhood TB. METHODS: Scoping review according to the PRISMA extension. The definitions considered for the selection followed the acronym PCC where the population (P) is children under 18 years of age with TB disease, the concept (C) refers to missed opportunities for prevention and diagnosis, and context (C) is defined as a diagnosis of TB disease. The authors searched systematically in the databases; VHL/Lilacs, Medline via PubMed, Cochrane, Scopus, and Web of Science, without date or language limitation. RESULTS: Seven studies were included. In developed countries, with low disease burden, the main shortcoming is the delay in diagnosing bacilliferous adults in contact with young children. This problem is concentrated in the portion of the population with socioeconomic vulnerability. In underdeveloped countries, with a high burden of disease, the biggest challenge is tracking children who come into contact with bacilliferous patients. CONCLUSIONS: There are still many missed opportunities in the prevention and diagnosis of childhood TB. The positive legacy of the COVID-19 pandemic should be taken advantage of and the encouragement of scientific development in the management of infectious diseases should be taken.

A deep learning model to predict Ki-67 positivity in oral squamous cell carcinoma.

Anatomical pathology is undergoing its third revolution, transitioning from analogical to digital pathology and incorporating new artificial intelligence technologies into clinical practice. Aside from classification, detection, and segmentation models, predictive models are gaining traction since they can impact diagnostic processes and laboratory activity, lowering consumable usage and turnaround time. Our research aimed to create a deep-learning model to generate synthetic Ki-67 immunohistochemistry from Haematoxylin and Eosin (H&E) stained images. We used 175 oral squamous cell carcinoma (OSCC) from the University Federico II's Pathology Unit's archives to train our model to generate 4 Tissue Micro Arrays (TMAs). We sectioned one slide from each TMA, first stained with H&E and then re-stained with anti-Ki-67 immunohistochemistry (IHC). In digitised slides, cores were disarrayed, and the matching cores of the 2 stained were aligned to construct a dataset to train a Pix2Pix algorithm to convert H&E images to IHC. Pathologists could recognise the synthetic images in only half of the cases in a specially designed likelihood test. Hence, our model produced realistic synthetic images. We next used QuPath to quantify IHC positivity, achieving remarkable levels of agreement between genuine and synthetic IHC. Furthermore, a categorical analysis employing 3 Ki-67 positivity cut-offs (5%, 10%, and 15%) revealed high positive-predictive values. Our model is a promising tool for collecting Ki-67 positivity information directly on H&E slides, reducing laboratory demand and improving patient management. It is also a valuable option for smaller laboratories to easily and quickly screen bioptic samples and prioritise them in a digital pathology workflow.

Association of tumor-infiltrating lymphocytes with recurrence score in hormone receptor-positive/HER2-negative breast cancer: Analysis of four prospective studies.

BACKGROUND: The clinical value of tumor infiltrating lymphocytes (TILs) in hormone receptor-positive (HR+)/HER2- breast cancer (BC) may be unearthed by focusing on more biologically aggressive tumors. Here we deepen and describe the correlation between RS and TILs, proposing an immuno-genomic model for HR+ /HER2- BC. METHODS: We enrolled T1-T3, N0-N1 BC patients with available RS® and TILs in the context of four multicenter, prospective studies. RS® and TILs were considered as continuous and categorical variables. RS® was categorized into: 0-10 (low risk), 11-25 (intermediate risk) and 26-100 (high risk); TILs were categorized into: low TILs (0-10%), intermediate TILs (11-59%) and high TILs (60-100%). RESULTS: 811 patients were included. RS distribution was (n = 810): low risk 22.0%, intermediate risk 61.2%, high risk 16.8%. TIL distribution was (n = 455): low TILs 84.6%, intermediate TILs 13.6% and high TILs 1.8%. A significant, weak positive, linear correlation was found between continuous TILs and RS (Pearson coefficient=0.223, p < 0.001). When considering RS and TILs categories, tumors with intermediate/high TIL levels significantly enriched the high RS subgroup (p = 0.006). This was confirmed both within Luminal A and Luminal B cohorts. Among high-RS patients, 16.7% of Luminal A and 26.7% of Luminal B tumors had intermediate/high TILs. CONCLUSIONS: We observed that RS® and TILs capture only slightly overlapping information on the biology of HR+ /HER2- tumor microenvironment. We demonstrated the feasibility of combining RS and TILs into a composite immuno-genomic model, which may serve the purpose of guiding and focalizing patient selection in the further development of immunotherapy strategies for Luminal-like disease.