Background-COX inhibitors and β-blockers were recently suggested to reduce cancer

No abstract

Treatment aimed at perioperative enhancement of CMI and simultaneous inhibition of excessive catecholamine and prostaglandin responses, employing CpG-C, propranolol, and etodolac, could be successful in limiting postoperative immunosuppression and metastatic progression, more so than each treatment alone.

Aire is a transcriptional regulator that induces the promiscuous expression of thousands of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs), a step critical for the induction of immunological self-tolerance. Studies have offered molecular insights into how Aire operates, but more comprehensive understanding of this process still remains elusive. Here we found abundant expression of the protein deacetylase Sirtuin-1 (Sirt1) in mature Aire(+) mTECs, wherein it was required for the expression of Aire-dependent TRA-encoding genes and the subsequent induction of immunological self-tolerance. Our study elucidates a previously unknown molecular mechanism for Aire-mediated transcriptional regulation and identifies a unique function for Sirt1 in preventing organ-specific autoimmunity.

Surgical resection of the primary tumor is a necessary and effective treatment for breast cancer patients. For various reasons discussed, we believe that the short postoperative period is critical for eliminating minimal residual disease (MRD), thus markedly impacting long term survival. Unfortunately, both animal and human studies have shown that surgery induces suppression of anti-metastatic cell-mediated immunity (CMI) at this critical period, which is suggested to worsen patients' prognosis. In this review we examine different aspects of the surgical procedure that cause immunosuppression (e.g., anesthesia and tissue damage), discuss their mediating humoral and cellular mechanisms, and suggest prophylactic interventions feasible in cancer patients to avoid postoperative suppression of CMI. The use of the suggested interventions has been shown to significantly reduce postoperative metastasis in animal models, including mammary adenocarcinoma, and initial data suggest similar efficacy in breast cancer patients. We believe that our recommended prophylactic interventions can easily be applied by health-care practitioners and hold promise in reducing long-term recurrence and metastasis in cancer patients.