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Cancer immunoediting is the process whereby immune cells protect against cancer formation by sculpting the immunogenicity of developing tumors. Although the full process depends on innate and adaptive immunity, it remains unclear whether innate immunity alone is capable of immunoediting. To determine whether the innate immune system can edit tumor cells in the absence of adaptive immunity, we compared the incidence and immunogenicity of 3'methylcholanthrene-induced sarcomas in syngeneic wild-type, RAG2(-/-), and RAG2(-/-)x γc(-/-) mice. We found that innate immune cells could manifest cancer immunoediting activity in the absence of adaptive immunity. This activity required natural killer (NK) cells and interferon γ (IFN-γ), which mediated the induction of M1 macrophages. M1 macrophages could be elicited by administration of CD40 agonists, thereby restoring editing activity in RAG2(-/-)x γc(-/-) mice. Our results suggest that in the absence of adaptive immunity, NK cell production of IFN-γ induces M1 macrophages, which act as important effectors during cancer immunoediting.

Cancer immunoediting is the process whereby immune cells protect against cancer formation by sculpting the immunogenicity of developing tumors. Although the full process depends on innate and adaptive immunity, it remains unclear whether innate immunity alone is capable of immunoediting. To determine whether the innate immune system can edit tumor cells in the absence of adaptive immunity, we compared the incidence and immunogenicity of 3'methylcholanthrene-induced sarcomas in syngeneic wild-type, RAG2(-/-), and RAG2(-/-)x γc(-/-) mice. We found that innate immune cells could manifest cancer immunoediting activity in the absence of adaptive immunity. This activity required natural killer (NK) cells and interferon γ (IFN-γ), which mediated the induction of M1 macrophages. M1 macrophages could be elicited by administration of CD40 agonists, thereby restoring editing activity in RAG2(-/-)x γc(-/-) mice. Our results suggest that in the absence of adaptive immunity, NK cell production of IFN-γ induces M1 macrophages, which act as important effectors during cancer immunoediting.

Focal segmental glomerulosclerosis (FSGS) is a syndrome that involves kidney podocyte dysfunction and causes chronic kidney disease. Multiple factors including chemical toxicity, inflammation, and infection underlie FSGS; however, highly penetrant disease genes have been identified in a small fraction of patients with a family history of FSGS. Variants of apolipoprotein L1 (APOL1) have been linked to FSGS in African Americans with HIV or hypertension, supporting the proposal that genetic factors enhance FSGS susceptibility. Here, we used sequencing to investigate whether genetics plays a role in the majority of FSGS cases that are identified as primary or sporadic FSGS and have no known cause. Given the limited number of biopsy-proven cases with ethnically matched controls, we devised an analytic strategy to identify and rank potential candidate genes and used an animal model for validation. Nine candidate FSGS susceptibility genes were identified in our patient cohort, and three were validated using a high-throughput mouse method that we developed. Specifically, we introduced a podocyte-specific, doxycycline-inducible transactivator into a murine embryonic stem cell line with an FSGS-susceptible genetic background that allows shRNA-mediated targeting of candidate genes in the adult kidney. Our analysis supports a broader role for genetic susceptibility of both sporadic and familial cases of FSGS and provides a tool to rapidly evaluate candidate FSGS-associated genes., Introduction The glomerulus of the kidney is a specialized capillary bed that generates an ultrafiltrate that, after modification by the kidney tubule system, becomes urine. Diseases of the glomerulus often [...]

Cancer immunoediting, the process by which the immune system controls tumour outgrowth and shapes tumour immunogenicity, is comprised of three phases: elimination, equilibrium and escape (1-5). Although many immune components that participate in this process are known, its underlying mechanisms remain poorly defined. A central tenet of cancer immunoediting is that T-cell recognition of tumour antigens drives the immunological destruction or sculpting of a developing cancer. However, our current understanding of tumour antigens comes largely from analyses of cancers that develop in immunocompetent hosts and thus may have already been edited. Little is known about the antigens expressed in nascent tumour cells, whether they are sufficient to induce protective antitumour immune responses or whether their expression is modulated by the immune system. Here, using massively parallel sequencing, we characterize expressed mutations in highly immunogenic methylcholanthrene-induced sarcomas derived from immunodeficient [Rag2.sup.-/-] mice that phenotypically resemble nascent primary tumour cells (1,3,5). Using class I prediction algorithms, we identify mutant spectrin-β2 as a potential rejection antigen of the d42m1 sarcoma and validate this prediction by conventional antigen expression cloning and detection. We also demonstrate that cancer immunoediting of d42m1 occurs via a T-cell-dependent immunoselection process that promotes outgrowth of pre-existing tumour cell clones lacking highly antigenic mutant spectrin-β2 and other potential strong antigens. These results demonstrate that the strong immunogenicity of an unedited tumour can be ascribed to expression of highly antigenic mutant proteins and show that outgrowth of tumour cells that lack these strong antigens via a T-cell-dependent immunoselection process represents one mechanism of cancer immunoediting., For this study, we chose two representative, highly immunogenic, unedited methylcholanthrene (MCA)-induced sarcoma cell lines, d42m1 and H31m1, derived from immunodeficient [Rag2.sup.-/-] mice (1). Both grow progressively when transplanted orthotopically [...]

A study is conducted to investigate the photoinduced oxidation of trimethyl acetate (TMA) on an atomically flat surface of rutile TiO2. The limited surface mobility of electrons photoexcited and trapped at OH-associated Ti sites is proposed to cause the temporal and spatial modulations.

Author(s): Craig H. Bassing [1]; Frederick W. Alt [1]; Maureen M. Hughes [2]; Margaux D'Auteuil [1]; Tara D. Wehrly [2]; Barbara B. Woodman [1]; Frank Gärtner [1]; J. Michael White [...]

A study was conducted to examine the physiological features of mice that lacks the Janus kinase Jak1. One genetic factor that was cited for the birth defects and subsequent perinatal death of the animals was the failure of Jak1 cells to biologically respond to cytokines. The results indicated the major role played by the kinase in promoting the biologic responses caused by cytokine receptors.

The janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathway has been shown to be involved in many biological processes. JAK proteins are bound to cytokine receptors and signaling is triggered when cytokine binding induces receptor dimerization whereas STAT proteins are activated by tyrosine phosphorylation to form homodimers and heterodimers that activate cytokine-inducible genes. However, there is no information regarding the mechanism by which pathway specificity is manifested. An experiment on mice deficient in STAT1 is discussed to elucidate this mechanism.

The surface sites associated with charge transfer and trapping is identified during the photodecomposition of an organic adsorbate using scanning tunneling microscopy, electron energy loss spectroscopy and photodesorption. The carboxylate moiety binds the molecule strongly to the surface and is the main anchoring point for most organic sensitizers.