Remodeled tumor immune microenvironment (TIME) parade via natural killer cells reprogramming in breast cancer.

Breast cancer (BC) is the main cause of cancer-related mortality among women globally. Despite substantial advances in the identification and management of primary tumors, traditional therapies including surgery, chemotherapy, and radiation cannot completely eliminate the danger of relapse and metastatic illness. Metastasis is controlled by microenvironmental and systemic mechanisms, including immunosurveillance. This led to the evolvement of immunotherapies that has gained much attention in the recent years for cancer treatment directed to the innate immune system. The long forgotten innate immune cells known as natural killer (NK) cells have emerged as novel targets for more effective therapeutics for BC. Normally, NK cells has the capacity to identify and eradicate tumor cells either directly or by releasing cytotoxic granules, chemokines and proinflammatory cytokines. Yet, NK cells are exposed to inhibitory signals by cancer cells, which causes them to become dysfunctional in the immunosuppressive tumor microenvironment (TME) in BC, supporting tumor escape and spread. Potential mechanisms of NK cell dysfunction in BC metastasis have been recently identified. Understanding these immunologic pathways driving BC metastasis will lead to improvements in the current immunotherapeutic strategies. In the current review, we highlight how BC evades immunosurveillance by rendering NK cells dysfunctional and we shed the light on novel NK cell- directed therapies.

Correction to: Protection from doxorubicin-induced nephrotoxicity by clindamycin: novel antioxidant, anti-inflammatory and anti-apoptotic roles.

The published online version contains mistake in the author list for the author "Nermeen N. El-Agroudy" was incorrectly presented.

Protection from doxorubicin-induced nephrotoxicity by clindamycin: novel antioxidant, anti-inflammatory and anti-apoptotic roles.

This study was performed to examine whether clindamycin could protect against doxorubicin (DOX)-induced acute nephrotoxicity, and if so, what molecular mechanisms responsible for this protective effect. Male albino rats were pretreated with clindamycin once per day for 5 consecutive days at a dose of 300 mg/kg, i.p, then received a single dose of DOX (15 mg/kg; i.p) on the 5th day. DOX-induced marked renal injury as indicated by the presence of inflammatory cell infiltration, congestion, and edema accompanied by elevation in serum levels of creatinine and urea. These effects were alleviated by clindamycin pretreatment. DOX caused glutathione depletion and reduction in level of the antioxidant enzyme, catalase. Pretreatment with clindamycin markedly prohibited DOX-induced oxidative damage in renal tissue. Moreover, DOX provoked inflammatory responses in renal tissues as confirmed by increased expressions of NF-κB and COX-2 which were significantly reduced by clindamycin pretreatment. Besides, DOX-triggered apoptotic cascades in renal tissues as evidenced by elevated expression of pro-apoptotic proteins; Bax and cytochrome c, enhancing activity of caspase-3 enzyme whereas reducing the expression of anti-apoptotic Bcl-2 protein. Clindamycin pretreatment counteracts these apoptotic effects of DOX. Summarily, our results provide an evidence for the first time that clindamycin has a potential protective action against DOX-induced acute nephrotoxicity through inhibiting oxidative stress, inflammatory cascades, and apoptotic tissue injury.