Mammographic density (MD) is one of the most important independent risk factors for breast cancer and can be defined as the relative proportion of radio-dense fibroglandular tissue to radio-lucent fatty tissue in the breast, as visualized in mammograms. Women with dense breasts have a four- to sixfold increased risk of breast cancer compared to women with fatty breasts,¹ and breast density has been shown to improve the accuracy of current risk prediction models.² The reliable identification of women at increased risk of developing breast cancer paves the way for the selective implementation of risk-reducing interventions.³ Additionally, dense tissue may mask cancers, reducing the sensitivity of mammography,⁴ and breast cancer mortality can be reduced if women at high risk are identified early and treated adequately.⁵ There is international interest in personalizing breast screening so that women with dense breasts are screened more regularly or with alternative or supplemental modalities.⁶

Background: Fulfilling the promise of cancer immunotherapy requires novel predictive biomarkers to characterise the host immune microenvironment. Deciphering the complexity of immune cell interactions requires an automated multiplex approach to histological analysis of tumour sections. We tested a new automatic approach to select tissue and quantify the frequencies of cell-cell spatial interactions occurring in the PD1/PD-L1 pathway, hypothesised to reflect immune escape in oropharyngeal squamous cell carcinoma (OPSCC). Methods: Single sections of diagnostic biopsies from 72 OPSCC patients were stained using multiplex immunofluorescence (CD8, PD1, PD-L1, CD68). Following multispectral scanning and automated regions-of-interest selection, the Hypothesised Interaction Distribution (HID) method quantified spatial proximity between cells. Method applicability was tested by investigating the prognostic significance of co-localised cells (within 30 μm) in patients stratified by HPV status. Results: High frequencies of proximal CD8⁺ and PD-L1⁺ (HR 2.95, p = 0.025) and PD1⁺ and PD-L1⁺ (HR 2.64, p = 0.042) cells were prognostic for poor overall survival in patients with HPV negative OPSCC (n = 31). Conclusion: The HID method can quantify spatial interactions considered to reflect immune escape and generate prognostic information in OPSCC. The new automated approach is ready to test in additional cohorts and its applicability should be explored in research and clinical studies.

Background: The incidence of endometrial cancer is rising in parallel with the obesity epidemic. Obesity increases endometrial cancer risk and weight loss is protective, but the underlying mechanisms are incompletely understood. We hypothesise that the immune microenvironment may influence susceptibility to malignant transformation in the endometrium. The aim of this study was to measure the impact of obesity and weight loss on the immunological landscape of the endometrium. Methods: We conducted a prospective cohort study of women with class III obesity (body mass index, BMI ≥ 40 kg/m²) undergoing bariatric surgery or medically-supervised low-calorie diet. We collected blood and endometrial samples at baseline, and two and 12 months after weight loss intervention. Serum was analysed for inflammatory markers CRP, IL-6 and TNF-α. Multiplex immunofluorescence was used to simultaneously identify cells positive for immune markers CD68, CD56, CD3, CD8, FOXP3 and PD-1 in formalin-fixed paraffin-embedded endometrial tissue sections. Kruskal–Wallis tests were used to determine whether changes in inflammatory and immune biomarkers were associated with weight loss. Results: Forty-three women with matched serum and tissue samples at all three time points were included in the analysis. Their median age and BMI were 44 years and 52 kg/m², respectively. Weight loss at 12 months was greater in women who received bariatric surgery (n = 37, median 63.3 kg) than low-calorie diet (n = 6, median 12.8 kg). There were significant reductions in serum CRP (p = 3.62 × 10⁻⁶, r = 0.570) and IL-6 (p = 0.0003, r = 0.459), but not TNF-α levels, with weight loss. Tissue immune cell densities were unchanged except for CD8+ cells, which increased significantly with weight loss (p = 0.0097, r = −0.323). Tissue CD3+ cell density correlated negatively with systemic IL-6 levels (p = 0.0376; r = −0.318). Conclusion: Weight loss is associated with reduced systemic inflammation and a recruitment of protective immune cell types to the endometrium, supporting the concept that immune surveillance may play a role in endometrial cancer prevention.

Classic Hodgkin lymphoma (cHL) has a rich immune infiltrate, which is an intrinsic component of the neoplastic process. Malignant Hodgkin Reed-Sternberg cells (HRSC) create an immunosuppressive microenvironment by the expression of regulatory molecules, preventing T-cell activation. It has also been demonstrated that mononuclear phagocytes (MNPs) in the vicinity of HRSC express similar regulatory mechanisms in parallel, and their presence in tissue is associated with inferior patient outcomes. MNPs in cHL have hitherto been identified with a small number of canonical markers and are usually described as 'tumor-associated macrophages'. The organization of MNP networks and interactions with HRSC remains unexplored at high resolution. Here, we defined the global immune cell composition of cHL and non-lymphoma lymph nodes, integrating data across single-cell RNA sequencing, spatial transcriptomics, and multiplexed immunofluorescence. We observed that MNPs comprise multiple subsets of monocytes, macrophages and dendritic cells (DCs). Classical monocytes, macrophages and conventional DC2 were enriched in the vicinity of HRSC, but plasmacytoid DCs and activated DCs were excluded. Unexpectedly, cDCs and monocytes expressed immunoregulatory checkpoints PD-L1, TIM-3, and the tryptophan-catabolizing protein IDO, at the same level as macrophages. Expression of these molecules increased with age. We also found that classical monocytes are important signaling hubs, potentially controlling the retention of cDC2 and ThExh via CCR1-, CCR4-, CCR5-, and CXCR3-dependent signaling. Enrichment of the cDC2-monocyte-macrophage network in diagnostic biopsies is associated with early treatment failure. These results reveal unanticipated complexity and spatial polarization within the MNP compartment, further demonstrating their potential roles in immune evasion by cHL.

Accurate prediction of individual breast cancer risk paves the way for personalised prevention and early detection. The incorporation of genetic information and breast density has been shown to improve predictions for existing models, but detailed image-based features are yet to be included despite correlating with risk. Complex information can be extracted from mammograms using deep-learning algorithms, however, this is a challenging area of research, partly due to the lack of data within the field, and partly due to the computational burden. We propose an attention-based Multiple Instance Learning (MIL) model that can make accurate, short-term risk predictions from mammograms taken prior to the detection of cancer at full resolution. Current screen-detected cancers are mixed in with priors during model development to promote the detection of features associated with risk specifically and features associated with cancer formation, in addition to alleviating data scarcity issues. MAI-risk achieves an AUC of 0.747 [0.711, 0.783] in cancer-free screening mammograms of women who went on to develop a screen-detected or interval cancer between 5 and 55 months, outperforming both IBIS (AUC 0.594 [0.557, 0.633]) and VAS (AUC 0.649 [0.614, 0.683]) alone when accounting for established clinical risk factors.

Percutaneous Nephrolithotomy (PCNL) is a procedure used to treat kidney stones. In PCNL, a needle punctures the kidney through an incision in a patient’s back and thin tools are threaded through the incision to gain access to kidney stones for removal. Despite being one of the main endoscopic procedures for managing kidney stones, PCNL remains a difficult procedure to learn with a long and steep learning curve. Virtual reality simulation with haptic feedback is emerging as a new method for PCNL training. It offers benefits for both novices and experienced surgeons. In the first case, novices can practice and gain kidney access in a variety of simulation scenarios without offering any risk to patients. In the second case, surgeons can use the simulator for preoperative surgical rehearsal. This paper proposes the first preliminary study of PCNL surgical rehearsal using the Marion Surgical PCNL simulator. Preoperative CT scans of a patient scheduled to undergo PCNL are used in the simulator to create a 3D model of the renal system. An experienced surgeon then planned and practiced the procedure in the simulator before performing the surgery in the operating room. This is the first study involving survival rehearsal using a combination of VR and haptic feedback in PCNL before surgery. Preliminary results confirm that surgical rehearsal using a combination of virtual reality and haptic feedback strongly affects decision making during the procedure.