Phenotype and Function of Activated Natural Killer Cells From Patients With Prostate Cancer: Patient-Dependent Responses to Priming and IL-2 Activation
FRONTIERS IN IMMUNOLOGY
Authors: Hood, Simon P.; Foulds, Gemma A.; Imrie, Heather; Reeder, Stephen; McArdle, Stephanie E. B.; Khan, Masood; Pockley, Alan Graham
Abstract
Background: Although immunotherapy has emerged as the "next generation" of cancer treatments, it has not yet been shown to be successful in the treatment of patients with prostate cancer, for whom therapeutic options remain limited to radiotherapy and androgen (hormone) deprivation therapy. Previous studies have shown that priming natural killer (NK) cells isolated from healthy individuals via co-incubation with CTV-1 cells derived from an acute lymphoblastic leukemia (ALL) enhances their cytotoxicity against human DU145 (metastatic) prostate cancer cells, but it remains unknown to what extent NK cells from patients with prostate cancer can be triggered to kill. Herein, we explore the phenotype of peripheral blood NK cells in patients with prostate cancer and compare the capacity of CTV-1 cell-mediated priming and IL-2 stimulation to trigger NK cell-mediated killing of the human PC3 (metastatic) prostate cancer cell line. Methods: The phenotype of resting, primed (co-incubation with CTV-1 cells for 17 h) and IL-2 activated (100 IU/ml IL-2 for 17 h) NK cells isolated from frozen-thawed peripheral blood mononuclear cell (PBMC) preparations from patients with benign disease (n = 6) and prostate cancer (n = 18) and their cytotoxicity against PC3 and K562 cells was determined by flow cytometry. Relationship(s) between NK cell phenotypic features and cytotoxic potential were interrogated using Spearman Rank correlation matrices. Results and Conclusions: NK cell priming and IL-2 activation of patient-derived NK cells resulted in similar levels of cytotoxicity, but distinct NK cell phenotypes. Importantly, the capacity of priming and IL-2 stimulation to trigger cytotoxicity was patient-dependent and mutually exclusive, in that NK cells from similar to 50% of patients preferentially responded to priming whereas NK cells from the remaining patients preferentially responded to cytokine stimulation. In addition to providing more insight into the biology of primed and cytokine-stimulated NK cells, this study supports the use of autologous NK cell-based immunotherapies for the treatment of prostate cancer. However, our findings also indicate that patients will need to be stratified according to their potential responsiveness to individual therapeutic approaches.
Hepatic volume profiles in potential living liver donors with anomalous right-sided ligamentum teres
ABDOMINAL RADIOLOGY
Authors: Jeong, So Yeong; Kim, Kyoung Won; Lee, Jeongjin; Jang, Jin Kyoo; Kwon, Heon-Ju; Song, Gi Won; Lee, Sung Gyu
Abstract
Purpose In living liver donors with rare anatomical anomaly of right-sided ligamentum teres (RSLT), right or left hemiliver procurement is commonly contraindicated. The purpose of this study was to evaluate the hepatic volume profiles in potential donors with RSLT using semi-automated CT volumetry (CTV). Methods Among 5535 potential donor candidates in our institution between April 2003 and May 2019, 23 cases of RSLT (0.4%) were included. Proportional liver volumes were measured using semi-automated CTV and compared with those of manual volumetry and intraoperative graft weights (seven surgical cases). Results The mean percentage volume of the right posterior section was significantly larger than that of the left hemiliver (38.5 +/- 8.4% vs. 23.3 +/- 5.7%,P < 0.001). Particularly in independent right lateral type, the mean percentage volume of the right posterior section was about two times larger to that of the left hemiliver (41.5% +/- 6.5% vs. 21.9% +/- 4.4%,P < 0.001), whereas the volume proportions of these two parts were similar between the two parts in bifurcation and trifurcation types (P = 0.810 and 0.979, respectively). Semi-automated CTV of corresponding whole liver, right posterior section, right anterior section, and left hemiliver showed strong correlations with manual CTV (r = 0.989-0.998;P < 0.001). For the seven surgical cases, the graft weights estimated by semi-automated CTV showed a significant correlation with intraoperative graft weights (r = 0.972;P < 0.001). Conclusion In independent right lateral type of RSLT, the right posterior section tends to be significantly larger than left hemiliver, and may be an alternative option for graft in potential living liver donors with this rare anatomical anomaly.