Killer-cell immunoglobulin-like receptors (KIR) are expressed by natural killer (NK) and effector T cells. Although KIR+ T cells accumulate in oncologic patients, their role in cancer immune response remains elusive. This study explored the role of KIR+CD8+ T cells in cancer immunosurveillance by analyzing their frequency at diagnosis in the blood of 249 patients (80 melanomas, 80 bladder cancers, and 89 ovarian cancers), their relationship with overall survival (OS) of patients, and their gene expression profiles. KIR2DL1+ CD8+ T cells expanded in the presence of HLA-C2-ligands in patients who survived, but it did not in patients who died. In contrast, presence of HLA-C1-ligands was associated with dose-dependent expansions of KIR2DL2/S2+ CD8+ T cells and with shorter OS. KIR interactions with their specific ligands profoundly impacted CD8+ T cell expression profiles, involving multiple signaling pathways, effector functions, the secretome, and consequently, the cellular microenvironment, which could impact their cancer immunosurveillance capacities. KIR2DL1/S1+ CD8+ T cells showed a gene expression signature related to efficient tumor immunosurveillance, whereas KIR2DL2/L3/S2+CD8+ T cells showed transcriptomic profiles related to suppressive anti-tumor responses. These results could be the basis for the discovery of new therapeutic targets so that the outcome of patients with cancer can be improved.

Bladder cancer (BC) represents a wide spectrum of diseases, ranging from recurrent non-invasive tumors to advanced stages that require intensive treatments. BC accounts for an estimated 500,000 new cases and 200,000 deaths worldwide every year. Understanding the biology of BC has changed how this disease is diagnosed and treated. Bladder cancer is highly immunogenic, involving innate and adaptive components of the immune system. Although little is still known of how immune cells respond to BC, immunotherapy with bacillus Calmette–Guérin (BCG) remains the gold standard in high-risk non-muscle invasive BC. For muscle-invasive BC and metastatic stages, immune checkpoint inhibitors targeting CTLA-4, PD-1, and PD-L1 have emerged as potent therapies, enhancing immune surveillance and tumor cell elimination. This review aims to unravel the immune responses involving innate and adaptive immune cells in BC that will contribute to establishing new and promising therapeutic options, while reviewing the immunotherapies currently in use in bladder cancer.

Background/Objectives: Androgen receptor-targeted agents have significantly improved the prognosis of metastatic hormone-sensitive prostate cancer (mHSPC). Prostate-specific antigen (PSA) levels are key prognostic markers, with rapid and deep reductions associated with better outcomes. This study aims to assess the association between the new PSA cut-offs and survival in mHSPC patients treated with Apalutamide. Methods: We conducted a multicentre, retrospective analysis of mHSPC patients treated with Apalutamide between March 2021 and January 2023. Overall survival (OS) and radiographic progression-free survival (rFPS) were analyzed and stratified by the following PSA ranges: 0.2 ng/mL. Cox regression was applied to identify variables associated with OS and rPFS. Results: Among 193 patients, 34.2% had de novo mHSPC, with the majority classified as M1b. A total of 58.2% (110) of our cohort achieved ultralow PSA levels, with 20.6% between 0.02 and 0.2 ng/mL, and 21.2% of PSA levels > 0.2 ng/mL. Most patients reached ultralow PSA within six months. Low-volume, metachronous, and M1a subgroups displayed a higher prevalence of patients reaching ultralow PSA levels. At 18 months, OS was 100% in the ultralow PSA group, 94.4% for the 0.02–0.2 ng/mL group, and 67.7% in the >0.2 ng/mL group. Similarly, rPFS at 18 months was 100%, 93.5%, and 50.7%, respectively. Cox regression revealed that both ultralow PSA levels and ISUP grade had a significant impact on OS (HR of 8.256 and 0.164, respectively). For rPFS, only ultralow PSA levels had a significant impact (HR = 0.085). Conclusions: This real-world study of mHSPC patients treated with Apalutamide plus ADT revealed that achieving ultralow PSA levels is strongly associated with better oncological outcomes.

Background: Immunotherapy is gaining great relevance in both non-muscle-invasive bladder cancer (NMIBC), with the use of bacille Calmette–Guerin (BCG), and in muscle-invasive BC (MIBC) with anti-checkpoint therapies blocking PD-1/PD-L1, CTLA-4/CD80-CD86, and, more recently, NKG2A/HLA-E interactions. Biomarkers are necessary to optimize the use of these therapies. Methods: We evaluated killer-cell immunoglobulin-like receptors (KIRs) and HLA-I genotyping and the expression of NK cell receptors in circulating T and NK lymphocytes at diagnosis in 325 consecutive BC patients (151 treated with BCG and 174 treated with other therapies), as well as in 648 patients with other cancers and 973 healthy donors as controls. The proliferation and production of cytokines and cytotoxicity were evaluated in peripheral blood mononuclear cells, stimulated in vitro with anti-CD3/CD28 or BCG, from selected patients based on HLA-B −21M/T dimorphism (NKG2A ligands). Results: The HLA-B −21M/T genotype showed opposing results in BC patients treated with BCG or other therapies. The MM genotype, compared to MT and TT, was associated with a longer 75th-percentile overall survival (not reached vs. 68.0 ± 13.7 and 52.0 ± 8.3 months, p = 0.034) in BCG, but a shorter (8.0 ± 2.4 vs. 21.0 ± 3.4 and 19.0 ± 4.9 months, p = 0.131) survival in other treatments. The HLA-B −21M/T genotype was an independent predictive parameter of the progression-free survival (HR = 2.08, p = 0.01) and the OS (HR = 2.059, p = 0.039) of BC patients treated with BCG, together with age and tumor histopathologic characteristics. The MM genotype was associated with higher counts of circulating CD56^bright, fewer KIR2DL1/L2⁺ NK cells, and lower NKG2A expression, but not with differential in vitro NK cell functionality. Conclusions: The HLA-B −21M/T is independently associated with BC patient outcomes and can help to optimize the use of new immunotherapies in these patients.

Chronic pelvic pain syndrome (CPPS) is permanent pelvic pain of unknown etiology. Current theories suggest a multifactorial origin for CPPS, including urinary pathologies, psychosocial factors, prostate inflammation, infection, central sensitization of the nervous system, and muscular contractures or fibrosis. As there are no defined treatment protocols for CPPS, a multimodal approach is recommended. The objective of this study was to evaluate the impact of a manual therapy treatment protocol on pain, urinary symptoms, and overall quality of life. Twenty-three men aged 47.36 ± 10.11 years were recruited consecutively by urologists practicing at two hospitals. All men presented prostatic tenderness with no other positive clinical history, urine cultures, or echography studies. Patients underwent six manual therapy sessions (three during the first week and three every two weeks after that) performed by a single osteopath or physiotherapist. The intervention protocol addressed the treatment of muscle structures, fascial mechanics, vascularization, innervation, emotional factors, and the need for information. The questionnaires used to evaluate outcomes included the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the International Prostate Symptoms Score (IPSS), and a Visual Analog Scale (VAS) for pain, and the Hospital Anxiety and Depression Scale (HADS). Data were evaluated using Chi-squared or paired difference tests by an external researcher. The mean NIH-CPSI scores recorded for our study cohort decreased by 7.69 points (30.92%; p<0.0005; 95% CI 4.02-10.52). IPSS measurements decreased by 3.20 points (22.18%; p=0.009; 95% CI 1.00-6.09), although the item addressing quality of life decreased by 1.67 points only (31.99%; p<0.0005; 95% CI 0.94-2.33). The VAS score also decreased by 2.20 points (38.6%; p<0.0005; 95% CI 1.45-2.73). Changes in HADS scores were not statistically significant. Based on patient responses, this case series revealed that manual therapy improved urinary symptoms, pain, and quality of life.

Background: The shortage of donor kidneys has prompted interest in using organs from donors with severe acute kidney injury (AKI), but robust data on outcomes from donors with AKIN stage 3 remain limited. Methods: This single-centre, retrospective cohort study compared outcomes of kidney transplants from deceased donors with AKIN stage 3 AKI to matched non-AKI donors (n = 57 per group; matched by donor age ±5 years, year of transplant, and major cardiovascular risk factors). Primary outcomes were delayed graft function (DGF), death-censored graft survival, and patient survival. Secondary outcomes included renal function at follow-up. Results: DGF occurred in 54.4% (31/57) of AKIN 3 recipients vs. 33.3% (19/57) of non-AKI recipients (risk difference 21.1%, 95% CI 3.1–39.2; p = 0.037). Five-year death-censored graft survival was 94.7% vs. 96.4% (HR 1.28, 95% CI 0.25–6.52; p = 0.645). Five-year patient survival was 84.8% vs. 84.0% (HR 0.96, 95% CI 0.30–3.05; p = 0.979). Median follow-up was 32 months. Conclusions: In this preliminary, selected kidneys from AKIN stage 3 donors yielded similar medium-term graft and patient survival to non-AKI donors, despite higher DGF incidence. Findings should be interpreted cautiously and confirmed in adequately powered, multicentre studies with extended follow-up.