Aurora kinase A (AURKA) belongs to the family of serine/threonine kinases, whose activation is necessary for cell division processes via regulation of mitosis. AURKA shows significantly higher expression in cancer tissues than in normal control tissues for multiple tumor types according to the TCGA database. Activation of AURKA has been demonstrated to play an important role in a wide range of cancers, and numerous AURKA substrates have been identified. AURKA-mediated phosphorylation can regulate the functions of AURKA substrates, some of which are mitosis regulators, tumor suppressors or oncogenes. In addition, enrichment of AURKA-interacting proteins with KEGG pathway and GO analysis have demonstrated that these proteins are involved in classic oncogenic pathways. All of this evidence favors the idea of AURKA as a target for cancer therapy, and some small molecules targeting AURKA have been discovered. These AURKA inhibitors (AKIs) have been tested in preclinical studies, and some of them have been subjected to clinical trials as monotherapies or in combination with classic chemotherapy or other targeted therapies.

CD4(+)FoxP3(+) regulatory T cells (Tregs) represent a major cellular mediator of cancer immune evasion. The expression of tumor necrosis factor receptor type II (TNFR2) on Tregs is reported to identify the maximally suppressive Treg population in both mice and human. We therefore investigated the phenotype and function of TNFR2(+) Tregs present in the peripheral blood (PB) of 43 lung cancer patients. Further, the association of TNFR2 expression on Tregs with clinicopathological factors was analyzed. The results showed that in the PB of lung cancer patients, Tregs expressed markedly higher levels of TNFR2 than conventional T cells (Tconvs). Expression of TNFR2 appeared to correlate better than CD25(+) and CD127(-) with FoxP3 expression. PB TNFR2(+) Tregs in lung cancer patients were more proliferative and expressed higher levels of the immunosuppressive molecule CTLA-4, and consequently more potently suppressed IFNγ production by cocultured CD8 CTLs. More importantly, higher TNFR2 expression levels on Tregs were associated with lymphatic invasion, distant metastasis and more advanced clinical stage of lung cancer patients. Therefore, our study suggests that TNFR2(+) Tregs play a role in promoting tumor progressive metastasis and expression of TNFR2 by PB Tregs may prove to be a useful prognostic marker in lung cancer patients.

Foxp3(+) Tregs have been known as a major regulator of immune homeostasis through their immunosuppressive function. Th17 lineage is a CD4(+) T cell subset that exerts its function by secreting proinflammatory cytokines and protecting host against microbial infections. The altered ratio between Foxp3(+) Tregs and Th17 cells plays an important role in the pathogenesis of immune-related diseases. Recent mice and human studies have demonstrated that Tregs can be reprogrammed into a novel population, IL-17(+)Foxp3(+) T cells, phenotypically and functionally resembling Th17 cells under the complicated cytokine stimulation. The identification of IL-17(+)Foxp3(+) T cells may provide a new understanding of therapy targeting Tregs and Th17 cells in autoimmune diseases and cancer. Here, we highlight significant data regarding the phenotype profile, origination, differentiation, and the pleiotropic functions of IL-17(+)Foxp3(+) T cells and the reciprocal relationships of these cells to Tregs and Th17 cells. Furthermore, the role of IL-17(+)Foxp3(+) T cells in tumorigenesis and clinical implications in cancer therapy are discussed in this review.

The intrinsic cytotoxicity of cell-free haemoglobin (Hb) has hampered the development of reliable Hb-based blood substitutes for over seven decades. Notably, recent evidence shows that the Hb deploys this cytotoxic attack against invading microbes, albeit, through an unknown mechanism. Here, we unraveled a rapid molecular reprogramming of the Hb structure-function triggered by virulent haemolytic pathogens that feed on the haem-iron. On direct contact with the microbe, the Hb unveils its latent antimicrobial potency, where multiple antimicrobial fragments are released, each harbouring coordinated 'dual-action centres': microbe binding and pseudoperoxidase (POX) cycle activity. The activated Hb fragments anchor onto the microbe while the juxtaposed POX instantly unleashes a localized oxidative shock, killing the pathogen-in-proximity. This concurrent action conceivably restricts the diffusion of free radicals. Furthermore, the host astutely protects itself from self-cytotoxicity by simultaneously releasing endogenous antioxidants. We found that this decryption mechanism of antimicrobial potency is conserved in the ancient invertebrate respiratory protein, indicating its fundamental significance. Our definition of dual-antimicrobial centres in the Hb provides vital clues for designing a safer Hb-based oxygen carrier blood substitute.