Senescent CD8+ T cells acquire NK cell-like innate functions to promote antitumor immunity.

It has been suggested that aging of the immune system (immunosenescence) results in a decline in the acquired immune response, which is associated with an increase in age-related tumorigenesis. T-cell senescence plays a critical role in immunosenescence and is involved in the age-related decline of the immune function, which increases susceptibility to certain cancers. However, it has been shown that CD8+ T cells with the senescent T-cell phenotype acquire an natural killer (NK) cell-like function and are involved in tumor elimination. Therefore, the role of senescent CD8+ T cells in tumor immunity remains to be elucidated. In this study, we investigated the role of senescent CD8+ T cells in tumor immunity. In a murine model of transferred with B16 melanoma, lung metastasis was significantly suppressed in aged mice (age ≥30 weeks) in comparison to young mice (age 6-10 weeks). We evaluated the cytotoxic activity of CD8+ T cells in vitro and found that CD8+ T cells from aged mice activated in vitro exhibited increased cytotoxic activity in comparison to those from young mice. We used Menin-deficient effector T cells as a model for senescent CD8+ T cells and found that cytotoxic activity and the expression of NK receptors were upregulated in Menin-deficient senescent CD8+ T cells. Furthermore, Menin-deficient CD8+ T cells can eliminate tumor cells in an antigen-independent manner. These results suggest that senescent effector CD8+ T cells may contribute to tumor immunity in the elderly by acquiring NK-like innate immune functions, such as antigen-independent cytotoxic activity.

Extended robot-assisted laparoscopic prostatectomy and extended pelvic lymph node dissection as a monotherapy in patients with very high-risk prostate cancer Patients.

BACKGROUND: Patients with very-high-risk prostate cancer (VHRPCa) have earlier biochemical recurrences (BCRs) and higher mortality rates. It remains unknown whether extended robot-assisted laparoscopic prostatectomy (eRALP) without neoadjuvant or adjuvant therapy can improve the outcomes of VHRPCa patients. We aimed to determine the feasibility and efficacy of eRALP as a form of monotherapy for VHRPCa. METHODS: Data from 76 men who were treated with eRALP without neoadjuvant/adjuvant therapy were analyzed. eRALP was performed using an extrafascial approach. Extended pelvic lymph node (LN) dissection (ePLND) included nodes above the external iliac axis, in the obturator fossa, and around the internal iliac artery up to the ureter. The outcome measures were BCR, treatment failure (defined as when the prostate-specific antigen level did not decrease to <0.1 ng/ml postoperatively), and urinary continence (UC). Kaplan-Meier, logistic regression, and Cox proportional-hazards model were used to analyze the data. RESULTS: The median operative time was 246 min, and median blood loss was 50 ml. Twenty-one patients experienced postoperative complications. Median follow-up was 25.2 months; 19.7% of patients had treatment failure. Three-year, BCR-free survival rate was 62.0%. Castration-resistant prostate cancer-free survival rate was 86.1%. Overall survival was 100%. In 55 patients who had complete postoperative UC data, 47 patients (85.5%) recovered from their UC within 12 months. Clinical stage cT3b was an independent preoperative treatment failure predictor (p = 0.035), and node positivity was an independent BCR predictor (p = 0.037). The small sample size and retrospective nature limited the study. CONCLUSIONS: This approach was safe and produced acceptable UC-recovery rates. Preoperative seminal vesicle invasion is associated with treatment failure, and pathological LN metastases are associated with BCR. Therefore, our results may help informed decisions about neoadjuvant or adjuvant therapies in VHRPCa cases. PRECIS: Extended robot-assisted laparoscopic prostatectomy and extended pelvic lymph node dissection without adjuvant therapy is safe and effective for some patients with very-high-risk prostate cancer. The clinical stage and node positivity status predicted monotherapy failure, which may indicate good adjuvant therapy candidate.

Patient-reported outcomes after open radical prostatectomy, laparoscopic radical prostatectomy and permanent prostate brachytherapy.

OBJECTIVE: To assess patient-reported outcomes after open radical prostatectomy, laparoscopic radical prostatectomy and permanent prostate brachytherapy. METHODS: patient-reported outcomes were evaluated using Expanded Prostate Cancer Index Composite scores at baseline and 1, 3, 6, 12 and 36 months after treatment, respectively, using differences from baseline scores. RESULTS: Urinary function was the same in the three groups at baseline, but worse after surgery than after permanent prostate brachytherapy until 12 months, and similar after open radical prostatectomy and permanent prostate brachytherapy and better than after laparoscopic radical prostatectomy at 36 months. Urinary bother was significantly worse at 1 month after surgery, but better after open radical prostatectomy than after permanent prostate brachytherapy and laparoscopic radical prostatectomy at 3 months, after which symptoms improved gradually in all groups. Obstructive/irritative symptoms were worse after permanent prostate brachytherapy than after open radical prostatectomy at 36 months, and worse after laparoscopic radical prostatectomy until 6 months. Urinary incontinence was worse after surgery, particularly after 1 month. This symptom returned to the baseline level at 12 months after open radical prostatectomy, but recovery after laparoscopic radical prostatectomy was slower. Bowel function after permanent prostate brachytherapy was significantly worse than after surgery at 1 month and this continued until 6 months. Bowel bother was slightly worse at 3 and 6 months after permanent prostate brachytherapy compared to these time points after surgery. CONCLUSION: Urinary function and bother were worst after laparoscopic radical prostatectomy, especially in the early postoperative phase, whereas urinary obstructive/irritative symptom, bowel function and bother were worse after permanent prostate brachytherapy. These findings are useful and informative for the treatment of patients with prostate cancer.

Prospective longitudinal outcomes of quality of life after laparoscopic radical prostatectomy compared with retropubic radical prostatectomy.

BACKGROUND: There have been few reports on health-related quality of life (HRQOL) after laparoscopic radical prostatectomy (LRP) in Japanese patients. The aim of this study is to assess changes in HRQOL during 36 months after LRP compared with retropubic radical prostatectomy (RRP). METHODS: The subjects were 105 consecutive patients treated with LRP between 2011 and 2012. HRQOL was evaluated using the International Prostate Symptom Score (IPSS), Medical Outcome Study 8-Items Short Form Health Survey (SF-8), and Expanded Prostate Cancer Index Composite (EPIC) at baseline and 1, 3, 6, 12 and 36 months after surgery. These results were compared with data for 107 consecutive patients treated with RRP between 2005 and 2007. The comparison between LRP and RRP was examined at every time point by Mann-Whitney U-test and chi-square test. Multiple linear regression analysis was used to identify independent factors related to the urinary domain in EPIC. RESULTS: The IPSS change was similar in both groups. The LRP group had a better SF-8 mental component summary score at baseline and a better SF-8 physical component summary score at 1 month after surgery. In EPIC, urinary function and bother were worse after LRP, but improved at 12 months and did not differ significantly from those after RRP; however, these factors then worsened again at 36 months after LRP. Urinary incontinence was also worse at 36 months after LRP, compared to RRP. In patients treated with nerve-sparing surgery, urinary function and urinary incontinence were similar and good at 12 and 36 months in both groups. Bowel function and bother, and sexual function and bother were similar in both groups and showed no changes from 12 to 36 months. Age and salvage radiotherapy were independent predictors of incontinence (daily use of two or more pads) in multivariate analysis. Surgical procedure was not an independent factor for incontinence, but incontinence defined as use of one pad or more was associated with the surgical procedure. CONCLUSIONS: Urinary function and bother at 36 months were worse after LRP than after RRP. Age, salvage radiotherapy and surgical procedure were associated with urinary incontinence after 36 months.

Primary adrenal leiomyosarcoma with lymph node metastasis: a case report.

BACKGROUND: Leiomyosarcomas typically originate in smooth muscle cell. Leiomyosarcoma potentially arising from the adrenal gland is an extremely rare mesenchymal tumors associated with delayed diagnosis and poor prognosis. CASE PRESENTATION: A 34-year-old man visited our department complaining of right hypochondriac pain. Computed tomography demonstrated a solid mass measuring 5.2 cm in diameter above the right kidney, corresponding to the right adrenal gland, and a lymph node mass, which appeared to have invaded the IVC wall. Right adrenalectomy and lymphadenectomy were performed. A microscopic examination revealed primary adrenal leiomyosarcoma with lymph node metastasis. No adjuvant therapy was performed, and the patient remains recurrence-free at 10 months postoperatively. CONCLUSIONS: We experienced a very rare case of primary adrenal leiomyosarcoma. Aggressive surgical resection including vascular reconstruction may be associated with improved survival.