Tumor-Experienced Human NK Cells Express High Levels of PD-L1 and Inhibit CD8+ T Cell Proliferation.

Natural Killer (NK) cells play a key role in cancer immunosurveillance. However, NK cells from cancer patients display an altered phenotype and impaired effector functions. In addition, evidence of a regulatory role for NK cells is emerging in diverse models of viral infection, transplantation, and autoimmunity. Here, we analyzed clear cell renal cell carcinoma (ccRCC) datasets from The Cancer Genome Atlas (TCGA) and observed that a higher expression of NK cell signature genes is associated with reduced survival. Analysis of fresh tumor samples from ccRCC patients unraveled the presence of a high frequency of tumor-infiltrating PD-L1+ NK cells, suggesting that these NK cells might exhibit immunoregulatory functions. In vitro, PD-L1 expression was induced on NK cells from healthy donors (HD) upon direct tumor cell recognition through NKG2D and was further up-regulated by monocyte-derived IL-18. Moreover, in vitro generated PD-L1hi NK cells displayed an activated phenotype and enhanced effector functions compared to PD-L1- NK cells, but simultaneously, they directly inhibited CD8+ T cell proliferation in a PD-L1-dependent manner. Our results suggest that tumors might drive the development of PD-L1-expressing NK cells that acquire immunoregulatory functions in humans. Hence, rational manipulation of these regulatory cells emerges as a possibility that may lead to improved anti-tumor immunity in cancer patients.

Renal tumor growth rate in patients with previously normal CT scan: Analysis of the initial stage of growth.

OBJECTIVE: Most of the studies regarding natural history of renal masses are based on active surveillance series and suggest that the renal masses have a slow growth rate. Nevertheless, only a few studies report the time between a normal computed tomography (CT) scan to the first detection of a tumor. We aimed to analyze the growth rate in newly diagnosed kidney tumors. MATERIAL AND METHODS: We analyzed patients with enhancing renal masses that developed after a normal CT scan, which was performed at most 12 months earlier. Variables examined included patient age, gender, tumor size, volume, tumor linear growth rate (LGR). All cases were surgically treated. Mann-Whitney U test was used to compare variables. A p<0.05 was considered as statistically significant. RESULTS: We found 31 patients with 33 lesions. Male to female ratio was 1.58 (19/12). The average age was 59.2 years (standard deviation [SD]±12.1), and the mean tumor size was 4.27 cm (SD±4.3). Tumor LGR was 0.87 cm/month (range: 0.28-1.66) and presumed to be 10.4 cm at 1 year (range: 3.36-19.9). Tumor LGR for time detection at <6 month or ≥6 months were 1.1 cm/month and 0.68 cm/month (range: 0.27-1.08 and 0.88-1.76, respectively; p=0.0004), respectively. Tumor LGRs for low- and high-grade tumors were 0.89 cm/month and 0.83 cm/month (p=0.65), respectively. Median volume was 36.1 cm3 (range: 2.61-143.7), and for low and high grade the median volumes were 27.9 cm3 and 47.6 cm3, respectively (p=0.54). Malignant pathology was present in 93.9 % (31 of 33) of masses (lesions). CONCLUSION: We found differences in tumor LGR in tumors detected before and after 6 months. We did not find any correlation between tumor growth rate and Fuhrman grade system, gender, histology, or age. We found the highest LGR published up to date.