For those of you who would like to take advantage of our Luck O' the Irish SALE but prefer not to make payments online, you are welcome to send us a check or money order in the amount of $114.12 for a 3-year AD-FREE Premium Service Bundle or $190.20 for a 5-year Bundle. Make checks or money orders payable in US funds to "Investor Village" and send to: Investor Village, P.O. Box 2958, Marrero, LA 70073.
As many of you know, we operate on the honor system around here. So, in closing out our Luck O' the Irish SALE, we wanted to advise those of you who plan to pay by check or money order that you can send a PM to Admin informing us of your intention. We will then upgrade your account for 7 days, allowing you to enjoy our ad-free premium service now and giving you a reasonable amount of time to get your payment in.
CONCLUSIONS Glucocorticoid excess affects significantly more genes in ACC than other hormones. In GC+ ACC, expression of steroid synthesis genes was elevated while immune-related genes were suppressed. o Normal adrenal cells express steroid synthesis genes but not immune-related genes. o Steroid synthesis genes were hypomethylated in GC+ cases, while no difference in methylation between GC+ and GC- cases was found for immune genes. o Furthermore, fewer infiltrating immune cells (T cells and NKT cells) were found in GC+ cases compared to GC-, suggesting that immune effects are due to changes in immune cell infiltrate rather than transcriptional changes. Tumor mutation burden was higher in GC+ ACC cases, which may be caused by the observed immune suppression or immune cell exclusion that may, in turn, be related to higher tolerance of non-self-antigens in GC+ cases. A published GR activity score showed no difference between GC+ and GC- cases, which may be due to locally high concentrations of GC in the adrenal gland regardless of systemic GC levels. o In contrast, immune infiltration into ACC tumors may be negatively affected by the exposure of lymph nodes to elevated GC activity. A newly derived gene signature predicts the highest frequency of GC+-like tumors in uveal and skin cutaneous melanomas. The observed reduced abundance of immune cells and immune-related transcripts in GC+ ACC provides insight into the mechanisms by which GC may limit response to ICI therapy. o GR antagonism may increase immune related transcripts or immune cell infiltration, thus promoting tumor immune response in GC+ ACC and other malignancies with elevated GC activity. o This hypothesis will be tested in a phase 1 oncology trial of relacorilant combined with ICI (CORT125134-551, NCT04373265).