Absence of cyclin-dependent kinase inhibitor p27 or p18 increases efficiency of iPSC generation without induction of iPSC genomic instability.

Mechanisms underlying the generation of induced pluripotent stem cells (iPSC) and keeping iPSC stability remain to be further defined. Accumulated evidences showed that iPSC reprogramming may be controlled by the cell-division-rate-dependent model. Here we reported effects of absence of mouse p27 or p18 on iPSC generation efficiency and genomic stability.

Oncolytic Virus-Mediated Targeting of PGE2 in the Tumor Alters the Immune Status and Sensitizes Established and Resistant Tumors to Immunotherapy.

Immunotherapies are highly promising cancer treatments, but understanding the factors mediating their resistance remains critical. Successes in randomized clinical testing have supported the growing appreciation that oncolytic virotherapies primarily act as immunotherapies. Here we identified prostaglandin E2 (PGE2) in the tumor as a key mediator of resistance to immunotherapies, including oncolytic vaccinia virotherapy.

Combination of IFNα and poly-I:C reprograms bladder cancer microenvironment for enhanced CTL attraction.

Background: BCG is a prototypal cancer immunotherapeutic factor currently approved of bladder cancer. In attempt to further enhance the effectiveness of immunotherapy of bladder cancer and, potentially, other malignancies, we evaluated the impact of BCG on local production of chemokines attracting the desirable effector CD8(+) T cells (CTLs) and undesirable myeloid-derived suppressor cell (MDSCs) and regulatory T(reg) cells, and the ability of bladder cancer tissues to attract CTLs.

Methods: Freshly resected bladder cancer tissues were either analyzed immediately or cultured ex vivo in the absence or presence of the tested factors.

The role of GM-CSF in enhancing immunotherapy of cancer.

Evaluation of: Kanerva A, Nokisalmi P, Diaconu I et al. Antiviral and anti-tumor T-cell immunity in patients treated with GM-CSF coding oncolytic adenovirus. Clin.

IL-18-primed helper NK cells collaborate with dendritic cells to promote recruitment of effector CD8+ T cells to the tumor microenvironment.

Chemokine-driven interactions of immune cells are essential for effective antitumor immunity. Human natural killer (NK) cells can be primed by the interleukin (IL)-1-related proinflammatory cytokine IL-18 for unique helper activity, which promotes dendritic cell (DC) activation and DC-mediated induction of type-1 immune responses against cancer. Here, we show that such IL-18-primed "helper" NK cells produce high levels of the immature DC (iDC)-attracting chemokines CCL3 and CCL4 upon exposure to tumor cells or the additional inflammatory signals IFN-α, IL-15, IL-12, or IL-2.

Dendritic cell-based therapeutic cancer vaccines: what we have and what we need.

Therapeutic cancer vaccines rely on the immune system to eliminate tumor cells. In contrast to chemotherapy or passive (adoptive) immunotherapies with antibodies or ex vivo-expanded T cells, therapeutic vaccines do not have a direct anti-tumor activity, but aim to reset patients' immune systems to achieve this goal. Recent identification of effective ways of enhancing immunogenicity of tumor-associated antigens, including the use of dendritic cells and other potent vectors of cancer vaccines, provide effective tools to induce high numbers of circulating tumor-specific T cells.

Type-1 polarized dendritic cells primed for high IL-12 production show enhanced activity as cancer vaccines.

While multiple pathways of dendritic cell (DC) maturation result in transient production of IL-12, fully mature DCs show reduced ability to produce IL-12p70 upon a subsequent interaction with Ag-specific T cells, limiting their in vivo performance as vaccines. Such "DC exhaustion" can be prevented by the presence of IFNgamma during the maturation of human DCs (type-1-polarization), resulting in improved induction of tumor-specific Th1 and CTL responses in vitro. Here, we show that type-1 polarization of mouse DCs strongly enhances their ability to induce CTL responses against a model tumor antigen, OVA, in vivo, promoting the induction of protective immunity against OVA-expressing EG7 lymphoma.

Rare-event analysis in flow cytometry.

Technical aspects of rare-event detection are discussed in this article in a practical context, with two real-life examples. A growing number of flow cytometry-based assays depend on rare-event detection for basic science and clinical applications.

A proapoptotic function of p21 in differentiating granulocytes.

p21(waf 1/cip 1) (p21), best known for its ability to regulate the cell cycle, has been noted also to exert cell cycle-independent effects on apoptosis and differentiation. Inhibition of apoptosis by p21 has been reported in hematopoietic models, particularly in monocytes exposed to apoptogenic agents. The effect of p21 on survival has not hitherto been analyzed during the myeloblast to granulocyte transition.

Consensual immunity: success-driven development of T-helper-1 and T-helper-2 responses.

Non-germline-encoded T- and B-cell receptors allow humans to effectively deal with rapidly mutating pathogens. Here, we argue that, in addition to determining the antigenic specificity of immune responses, the same receptor systems can also regulate the T-helper-1/T-helper-2 profile of immunity. Such a mechanism--based on feedback from distinct effector cells to dendritic cells, rather than on instruction from pathogens--uses the effectiveness of particular effector cells at targeting and destroying a pathogen as a reliable, experience-based criterion to induce and maintain the appropriately polarized response.

Signal transduction pathways leading to cell cycle arrest and apoptosis induction in cancer cells by Allium vegetable-derived organosulfur compounds: a review.

Epidemiological studies continue to support the premise that dietary intake of Allium vegetables (e.g., garlic, onions and so forth) may lower the risk of various types of cancer.

Intratumoral delivery of dendritic cells engineered to secrete both interleukin (IL)-12 and IL-18 effectively treats local and distant disease in association with broadly reactive Tc1-type immunity.

Dendritic cells (DCs) were adenovirally engineered to constitutively and durably secrete the potent Th1-biasing cytokines interleukin (IL)-12 (AdIL12DC) and/or IL-18 (AdIL18DC) and evaluated for their ability to promote therapeutic antitumor immunity in murine sarcoma models. Injection of either AdIL12DC or AdIL18DC into day 7 CMS4 or MethA tumors resulted in tumor rejection or slowed tumor growth when compared with control cohorts. Importantly, intratumoral injection with DCs engineered to secrete both IL-12 and IL-18 (AdIL12/IL18DC) resulted in complete and the most acute rejection of any treatment group analyzed.