(1). Background: Immunohistochemical (IHC) evaluation of programmed death-1 (PD-1) and its ligand (PD-L1) is being used to evaluate advanced malignancies with potential response to immune checkpoint inhibitors. We evaluated both plasma and tissue expression of PD-1 and PD-L1 in the same cohort of patients, including non-metastatic and metastatic clear cell renal cell carcinoma (CCRCC). Concomitant plasma and tissue expression of PD-1 and PD-L1 was evaluated with emphasis on diagnostic and prognostic implications. (2) Methods: we analyzed PD-1 and PD-L1 IHC expression in tumor tissues and soluble forms (sPD-1 and sPD-L1) in plasma from 89 patients with CCRCC, of which 23 were metastatic and 16 received systemic therapy. The primary endpoint was evaluation of overall survival using Kaplan-Meier analysis and the Cox regression model. Plasma samples from healthy volunteers were also evaluated. (3) Results: Interestingly, sPD-1 and sPD-L1 levels were lower in cancer patients than in controls. sPD-1 and sPD-L1 levels and their counterpart tissue expression both at the tumor center and infiltrating front were not associated. Higher expression of both PD-1 and PD-L1 were associated with tumor grade, necrosis and tumor size. PD-1 was associated to tumor stage (pT) and PD-L1 to metastases. sPD-1 and sPD-L1 were not associated with clinico-pathological parameters, although both were higher in patients with synchronous metastases compared to metachronous ones and sPD-L1 was also higher for metastatic patients compared to non-metastatic patients. sPD-1 was also associated with the International Metastatic Renal Cell Cancer Database Consortium (IMDC) prognostic groups in metastatic CCRCC and also to the Morphology, Attenuation, Size and Structure (MASS) response criteria in metastatic patients treated with systemic therapy, mainly tyrosine-kinase inhibitors. Regarding prognosis, PD-L1 immunostaining at the tumor center with and without the tumor front was associated with worse survival, and so was sPD-L1 at a cut-off >793 ng/mL. Combination of positivity at both the tissue and plasma level increased the level of significance to predict prognosis. (4) Conclusions: Our findings corroborate the role of PD-L1 IHC to evaluate prognosis in CCRCC and present novel data on the usefulness of plasma sPD-L1 as a promising biomarker of survival in this neoplasia.

(1) Background: Renal cancer is one of the most frequent malignancies in Western countries, with an unpredictable clinical outcome, partly due to its high heterogeneity and the scarcity of reliable biomarkers of tumour progression. (Pro)renin receptor (PRR) is a novel receptor of the renin–angiotensin system (RAS) that has been associated with the development and progression of some solid tumours by RAS-dependent and -independent mechanisms. (2) Methods: In this study, we analysed the immunohistochemical expression of PRR at the centre and border in a series of 83 clear-cell renal cell (CCRCCs), 19 papillary (PRCC) and 7 chromophobe (ChRCC) renal cell carcinomas, and the benign tumour renal oncocytoma (RO, n = 11). (3) Results: PRR is expressed in all the tumour subtypes, with higher mean staining intensity in ChRCCs and ROs. A high expression of PRR at the tumour centre and at the infiltrative front of CCRCC tissues is significantly associated with high grade, tumour diameter, local invasion and stage, and with high mortality risk by UCLA integrated staging system (UISS) scale. (4) Conclusions: These findings indicate that PRR is associated with the development and progression of renal tumours. Its potential as a novel biomarker for RCC diagnosis/prognosis and as a promising therapeutic target should be taken into account in the future.

Renal cell carcinoma (RCC) ranks among the most prevalent malignancies in Western countries, marked by its notable heterogeneity, which contributes to an unpredictable clinical trajectory. The insufficiency of dependable biomarkers adds complexity to assessing this tumor progression. Imbalances of several components of the intrarenal renin–angiotensin system (iRAS) significantly impact patient prognoses and responses to first-line immunotherapies. In this study, we analyzed the immunohistochemical expression of the Mas-related G-protein-coupled receptor D (MrgD), which recognizes the novel RAS peptide alamandine (ALA), in a series of 87 clear cell renal cell (CCRCCs), 19 papillary (PRCC), 7 chromophobe (ChRCC) renal cell carcinomas, and 11 renal oncocytomas (RO). MrgD was expressed in all the renal tumor subtypes, with a higher mean staining intensity in the PRCCs, ChRCCs, and ROs. A high expression of MrgD at the tumor center and at the infiltrative front of CCRCC tissues was significantly associated with a high histological grade, large tumor diameter, local invasion, and locoregional node and distant metastasis. Patients with worse 5-year cancer-specific survival and a poorer response to antiangiogenic tyrosine-kinase inhibitors (TKIs) showed higher MrgD expression at the center of their primary tumors. These findings suggest a possible role of MrgD in renal carcinogenetic processes. Further studies are necessary to unveil its potential as a novel biomarker for CCRCC prognosis and response to frontline therapies.

Metastatic hormone-naïve prostate cancer (mHNPC) is an infrequent form of this tumour type that is characterized by metastasis at the time of diagnosis and accounts for 50% of prostate cancer-related deaths. Despite the extensive characterization of localized and metastatic castration resistant prostate cancer (mCRPC), the molecular characteristics of mHNPC remain largely unexplored. Here we provide the first extensive transcriptomics characterization of mHNPC. We generated discovery and validation bulk and single-cell RNA-Seq datasets and performed integrative computational analysis in combination with experimental studies. Our results provide unprecedented evidence of the distinctive transcriptional profile of mHNPC and identify stroma remodelling as a predominant feature of these tumours. Importantly, we discover a central role for the transcription factor SOX11 in triggering a heterotypic communication that is associated to the acquisition of metastatic properties. Our study will constitute an invaluable resource for a profound understanding of mHNPC that can influence patient management.

Among the extensive genomic alterations in prostate cancer, the genomic deletion of PTEN stands out as one of the most consistently observed and confirmed alteration. PTEN loss in prostate tumors is primarily associated with cancer cell proliferation and survival through the activation of the PI3K-AKT-mTOR signalling pathway. However, its use as a robust biomarker in the clinical practice is hampered by the complex epigenetic, transcriptional and post-translational regulation. Here, we undertook an approach that combined in situ assessment of PTEN protein with transcriptional surrogates of its activity to gain insights into the downstream functional effects of PTEN loss in primary tumors. Our extensive bioinformatic analyses, including the integration with single-cell RNA-Seq approaches in a new clinical cohort, highlighted stroma remodeling as the major cancer cell-extrinsic process associated with PTEN loss. By applying similar computational strategy on the transcriptomic data generated from primary prostate tumors of genetically engineered Pten knock-out mouse models, we validated the causal role of Pten in the stromal reaction observed in clinical specimens. Mechanistically, we provide evidence for the activation of a paracrine program that encompasses enhanced TGF-β signalling and that is compatible with the secretome of PTEN-deficient senescent cancer cells. Our study provides relevant biological context to the cellular and molecular alterations unleashed upon PTEN protein loss.

This study aims to analyze the contribution of 3D printing to the teaching and development of robotic partial nephrectomy (RNP) for renal tumors. Evaluation of results in planning the technique, which may vary depending on the professional performing it. A prospective study involving 32 patients who were susceptible to undergoing RPN for renal tumor. Surgical planning (SP) by senior, junior, and resident surgeons was analyzed based on three variables: (1) Tomography (2D), (2) Three-dimensional (3D) tomography, and (3) With a 3D printed model. Three consecutive pre-surgery SP questionnaires were administered. A usability test was completed after surgery. The cohort has a high R.E.N.A.L. score (41% intermediate and 21% high). The use of the 3D printed model changes the SP relative to the CT image by 25.60% and 20.11% with the 3D CT image. The SP factor that varies the most with 3D printing is that related to vascular anatomy (43.84% - 56.82%), followed by assessment of tumor depth (37.67% - 43.18%). Senior urologists modified the vascular hilum passage by up to 63.16%, compared to less than 12.5% by junior urologists. Feelings of security (55.3%), stress (4%), assessment of vascular anatomy (58.9%), tumor depth (36.45%), and surgical time (30.4%) improved. 3D printing influences planning regardless of the professional level, improves safety, and decreases surgical time. Senior surgeons significantly modify the SP more when assessing vascular anatomy by proposing more advanced surgeries.