14 The HLA-A and HLA-B alleles and KIR frequencies were expressed in percentages. The degree of association between each

group was expressed as the odds ratio (OR), which was calculated according to Woolf’s formula. Significance of the observed association was determined using the Chi-square test and corrected by Yates or Fisher’s exact test, two-tailed with 95% confidence intervals (95% see more CI). P < 0·05 was considered significant. Deviation from Hardy–Weinberg equilibrium was tested using a chi-squared test goodness-of-fit test for each locus. We genotyped KIR3DS1/3DL1 and HLA-A and B alleles in 23 HIV discordant couples, 100 HIV-1+ patients and 200 healthy controls. The results of the HESN participants were compared with each group (Table 1). We found a significant increase of receptor KIR3DS1(3DS1/3DL1) (homozygous and heterozygous forms) in HESN participants versus HIV-1+ partners (OR = 24,

selleckchem P = 0·00003), versus HIV-1+ group (OR = 8·15, P = 0·00066) and versus control group (OR = 4·26, P = 0·0026). On the other hand, the KIR3DL1/KIR3DL1 homozygosity was significantly decreased in the HESN participants with respect to discordant partners (OR = 0·04, P = 0·00003), to the HIV-1+ group (OR = 0·12, P = 0·00048) and to the control group (OR = 0·23, P = 0·026). When the HLA-Bw4 alleles (loci A and B) were examined, no differences were found between the groups. If we differentiate between Bw4-80I and Bw4-80T, a higher Florfenicol frequency of Bw4-80T was observed in the HESN participants versus discordant partners (OR = 5·13, P = 0·049). A significant increase of the KIR3DS1(3DS1/3DL1)/Bw4 combination was found in the HESN group compared with their HIV-1+ partners (OR = 15·24, P = 0·0003), with the HIV-1+ patients (OR = 6·86, P = 0·0001) and with the controls (OR = 2·74, P = 0·049). Bw4 alleles present in HESN participants

were: A*23, A*24, A*25, A*32, B*27, B*38, B* 44, B*51, B*52, B*57. We found a significant increase of HLA-A*32 in HESN participants versus HIV-1+ partners (OR = undefined, P = 0·009), versus HIV-1+ group (OR = 43·3, P = 0·00002) and versus control group (OR = 7·52, P = 0·0007). Besides an increase of HLA-B*44 in HESN participants compared with HIV-1+ partners (OR = 5·13, P = 0·049), versus the HIV-1+ group (OR = 8·85, P = 0·0001) and versus the control group (OR = 3·76, P = 0·005; Table 2). Similar results were obtained when we analysed those alleles in combination with KIR3DS1(3DS1/3DL1). For HLA-B*44, the medium resolution method used in this study allowed us to observe that nine of the ten alleles found in the HESN group were 4403/07/13 and only one was 4469. In the discordant HIV-1+ group of the three HLA-B*44 alleles, two were 4402/11/19 and one was 4405. The KIR3DS1 receptor was not present in the three HIV-1+ individuals carrying these alleles.

The more severe clinical disease and the presence of circulating inflammatory cytokines in these A350V/L351P KI mice when compared with R258W KI mice probably reflect an intrinsically more hyperactive NLRP3 inflammasome 10. This may arise from the, as yet, undefined effects of the background strain on inflammasome activity, since R258W KI mice exhibit less severe disease when interbred with BALB/c mice. A similar factor could account for the variable penetrance of CAPS disease in humans. The primary cells responsible for inducing disease in the R258W KI mice were shown to be hematopoietic cells, as bone marrow Ku0059436 cells from R258W KI mice (but

not from WT mice) transferred to irradiated WT recipients resulted in autoinflammation. In addition, inflamed KI

mice resolved the inflammation upon irradiation followed by bone marrow transfer from WT donor mice (9 and Meng and Strober, unpublished observation). A similar conclusion applies to A350V and L351P KI mice, as the disease observed in mice in which the mutation was limited to APC exhibited a similar www.selleckchem.com/products/z-vad-fmk.html phenotype to those mice in which the mutation occurred in all cells 10. It should be noted, however, that other cells could also be contributing to disease manifestations 22, 23. Furthermore, cells induced by APC, such as T cells, could also be contributing to inflammation as indicated by the fact that in R258W KI mice inflammation exhibits a Th17-cell bias that may be shaping the overall response (see Nature of inflammation in NLRP3-mutated mice). Studies showing that L351P KI mice crossed with RAG1-deficient mice that do not have T cells have largely undiminished disease do not contradict this point, as it is possible that the hyper-robust inflammasome activity Ureohydrolase in these mice might not model the lesser degree of inflammation in humans with CAPS. Detailed studies of the immune response underlying the inflammation in R258W KI mice have revealed

important new insights into how a hyperactive NLRP3 inflammasome causes inflammation. In initial studies, it was shown by RT-PCR examination of the spontaneously occurring skin lesions that the inflammation was associated with an increase in IL-17 family cytokines and factors, including IL-17A, IL-17F, IL-21, RORγt and IL-22, whereas, in contrast, the Th1 cytokine IFN-γ was only moderately elevated. In addition, other Th1 factors, such as IL-12Rβ2 and T-bet, were even decreased compared with levels in WT skin. Finally, the inflamed skin contained increased expression of a spectrum of proinflammatory cytokines including IL-12p40, IL-12p35, IL-1β, IL-6 and TNF-α. In further studies, this bias toward a Th17-cell-mediated inflammation was also observed in skin DTH responses in A350V/L351P KI mice as compared with WT mice 9.

1c). E7AS partially and completely blocked IL-32 and COX-2 expression, respectively (Fig. 1c), suggesting that factors other than COX-2 can induce IL-32. It has been reported that a single siRNA targeting the E7 coding region should inhibit the expression of both E6 and E7 proteins simultaneously31 and so E7AS could completely block COX-2 expression. Immunohistochemical staining for both COX-2 and IL-32 revealed the co-localization of these signals in invasive primary cancerous tissues (Fig. 1d). Expressed E7 induced significant increases in the activities of both the IL-32 and COX-2 promoters. As shown in Fig. 2, the HPV-16 E7 oncogene stimulated the promoter activities of DMXAA order both IL-32 (Fig. 2a) and COX-2 (Fig. 2b)

in a variety of cervical cancer cell lines, and E7AS specifically neutralized the E7-mediated activation of both the IL-32 (−746/+25) and COX-2 (−880/+9) promoters. In Fig. 2(a), there was no significant increase of IL-32 promoter activity induced by the control IL-32p itself (without E7) in the C33A/pOPI3 control cells (data not shown). Nor was there a significant increase of COX-2 promoter activity induced by the control E7 itself (without COX-2p) in the C33A/pOPI3 cells (Fig. 2b, data not shown). To determine the mechanism underlying the HPV-16 E7-mediated stimulation of COX-2 and IL-32, COX-2 was over-expressed in SiHa and CaSki cells and IL-32

expression was evaluated with RT-PCR and Western blot analyses. The IL-32 mRNA and protein expression levels were increased by COX-2 over-expression (Fig. 3a). In addition, IL-32 and E7 expressions were reduced in a check details dose-dependent manner by treatment with the COX-2-specific inhibitor NS398 in SiHa and CaSki cells (Fig. 3b). The levels of COX-2-derived PGE2 were reduced in the culture media from the NS398-treated SiHa and CaSki cells. Interleukin-32 levels were determined in the supernatants of COX-2 over-expressing and NS398-treated SiHa and CaSki cells using a sandwich IL-32 ELISA as reported Abiraterone previously,30 and significant expression levels of IL-32 were not detected in the culture media (data not shown) compared with the intracellular expression levels of IL-32. This result

supports the notion that IL-32 would not be secreted from cells as reported previously.12,26 Collectively, these data show that COX-2 is an upstream regulatory factor of HPV-16 E7-mediated IL-32 stimulation. To assess the regulatory effects of IL-32 on the expression of COX-2 mediated by the HPV-16 E7 oncogene in cervical cancer cells, SiHa and CaSki cells were transfected with IL-32γ and IL-32 siRNA, respectively, in independent experiments. The results of RT-PCR and Western blot analyses demonstrated that E7 and COX-2 were down-regulated in cells (over-expressed with IL-32γ) over-expressing IL-32γ and recovered by IL-32 siRNA (Figs 4a and 5a). The broad band of IL-32 proteins detected by Western blotting as shown in Fig. 3(b), suggested the various expressed forms of IL-32 proteins.

The majority used on a cross-sectional design, selleck screening library with only three studies utilising a cohort and two a case–control design. While 17 studies used population-based survey data or baseline data of ongoing trials, eight studies were based on clinical samples of women from one to 115 health facilities. The definitions used to assess ‘early sexual debut’ varied substantially between studies. Some studies defined early

sexual debut as the sexual debut occurring before the age 14, while others used 19 as their cut-off age. In addition, several studies measured age at first sex continuously or using more than one age intervals. As a result, for example, they compared the risk of HIV infection of women who had their sexual debut before the age of 15 to that of women whose sexual debut was after the age of 25, and not to that of women who had their first sex at the BGB324 chemical structure age of 15 or afterwards. Of the 25 studies included in this review, none was rated to have a high quality, seven to have medium quality, 13 to have low quality and five to have very low quality. Study sites included South Africa (six sites), Zimbabwe (six sites), Tanzania (four sites), Cameroon (three sites), Kenya (two sites), Rwanda (two sites), Malawi (one site), Nigeria (one site), Ghana (one site),

and one study was a four-city study in Cotonou, Benin, Yaounde, Cameroon, Kisumu, Kenya and Ndola, Zambia. Of the 26 results in the 23 articles, which reported unadjusted associations MYO10 between early sexual debut and women’s increased HIV infection risk, 13 found a significant association. As can be seen in Table 2, if studies that measured age at first sex as a continuous variable are not considered in the analysis, 12 of 21 found a significant association. Similarly, if only studies with a sample size above 300 are considered, 13 of 25 found a significant association. Importantly, all five studies with a sample size above 3000 found a significant association between early sex and HIV infection. In addition, among those studies with at least a medium quality score, five of seven studies report a significant unadjusted association between

early sexual debut and women’s increased HIV risk. In practice, in the studies reviewed, different authors controlled for different variables in subsequent multivariate analyses. Studies controlling for duration of sexual activity, women’s sexual risk behaviour, partner’s higher HIV infection risk and socio-demographic variables will be discussed separately. Surprisingly, only two studies, both from Zimbabwe and both of medium quality, controlled for women’s duration of sexual activity in their multivariate analysis (Table 3). In both cases, the association remained significant, suggesting that women who start sex at a young age are not solely at increased HIV risk because they are simply exposed to HIV risk for longer by being sexually active.

Cass et al.[2] have shown that although not all indigenous groups are affected equally by end-stage kidney disease there are some communities where the rates are about 20 times higher than the national figure, accelerating over the past few years in conjunction with coexisting conditions of type II diabetes and ischaemic heart disease (Fig. 1, Table 1). Information about patients who decline renal replacement therapy and opt for the ‘Conservative pathway’ is more difficult to access, however one small survey earlier by Catford[3] found that 35% of Aboriginal end-stage renal failure patients living on South buy MDV3100 Australia’s Anangu Pitjantjatjara Lands had refused treatment. Recent data on this not available,

however, as evident in the Chronic Kidney Disease database in Central Australia, the number of patients declining renal replacement therapy in this region are currently lower than the figures suggested above. Culture is an important part of the context within which all people including healthcare professionals understand their world and make decisions about how to act. In their articles Paul[4] and Muller

and Desmond[5] have shown that along with personal psychology and life experiences, culture fundamentally shapes the way people make meaning out of illness, suffering and dying. Failure to take culture seriously may mean that we elevate our own values and Abiraterone in vitro fail to understand the value systems held by people of different backgrounds. In addition these studies[4, 5] indicate that this may lead to problems such as lack of trust, increased desire for futile aggressive care

at the end of life, unnecessary physical/emotional and spiritual suffering, lack of faith in the physician, lack of adherence to the treatment regimen and dissatisfaction with care. In an ideal situation, for patients who choose the non-dialysis pathway, clinicians should discuss advance directives and advance care planning with the person and their family members to document the goals of care. Unlike their Western counterparts, advance care planning Demeclocycline is not common practice for most ATSI people. Some will not see the necessity to draw up an end of life plan due to sensitivities around issues of death. Oprah Fried[7, 8] in her reflections from Central Australia has commented that nearly all would want to die at home or on their ‘country’. Country’ refers to a particular area of land where they and their ancestors were born, lived and died. Sullivan et al.[1] in their study have highlighted several barriers to providing effective supportive care to ATSI people. These include: poor literacy and education levels; high mobility; poor housing and overcrowding; high levels of domestic violence and substance misuse; low income levels; poor underlying health; fear and dislike of hospitals, of the health system and officials; fear and distress of non-indigenous people coming to their homes and remoteness.

In this preliminary study, the results showed that there was an upregulated tendency after treatment with IVIG,, although considerable samples was sustained low expression Linsitinib price of NKG2D, which might be related to relative short time to be revaluated after IVIG therapy. The levels of NKG2D expression on CD3−CD56+NKG2D+ NK cells were increased

in 20 children who received therapy with IVIG. The levels of NKG2D expression on CD8+T cells in 30 children with KD after IVIG treatment were detected to be higher than those before the therapy (shown in Fig. 3). The MFI of NKG2D expression on CD3−CD56+NKG2D+ NK cells was increased in 22 children who received therapy with IVIG. The MFI of NKG2D expression on CD8+T cells in 29 children with KD after IVIG

treatment was detected to be higher than those before the therapy (shown in Fig. 3). Rea1-time PCR was used to evaluate the mRNA levels of cytokines such as IL-1β, IL-6 and TNF-α. As shown in Fig. 4, compared with healthy controls, the expression levels of IL-1β (5.12E-01 ± 1.78E-01 versus 8.85E-02 ± 3.13E-02, t = 14.89, P < 0.05), IL-6 (4.22E-03 ± 2.31E-03 versus 1.72E-03 ± 1.35E-03, t = 5.944, P < 0.05) and TNF-α (1.19E-01 ± 5.12E-02 versus see more 1.16E-02 ± 6.10E-03, t = 13.903, P < 0.05) were significantly upregulated during acute phase of KD. The levels Sclareol of IL-1β (1.06E-01 ± 5.09E-02, t = 13.768, P < 0.05), IL-6 (1.48E-03 ± 8.10E-04,

t = 7.590, P < 0.05) and TNF-α (3.03E-02 ± 2.48E-02, t = 10.469, P < 0.05) expression were decreased to some extents after therapy with IVIG. In addition, transcription levels of proinflammatory cytokines [IL-1β (6.12E-01 ± 2.19E-01 versus 4.59E-01 ± 1.26E-01, t = 2.576, P < 0.05), IL-6 (6.41E-03 ± 1.66E-03 versus 3.05E-03 ± 1.67E-03, t = 2.419, P < 0.05) and TNF-α (1.51E-01 ± 6.74E-02 versus 1.02E-01 ± 3.10E-02, t = 2.757, P < 0.05)] in KD-CAL+ patients with coronary artery lesion were detected to be higher than those in patients with KD-CAL−. It has been reported that IL-7 and IL-15 induce the expression of NKG2D on immunocompetent cells, and NKG2D can be downregulated on these cells by IL-12, TGF-β and IFN-γ [8-12] (Table 4). In this study, the plasma concentration of cytokines in KD was detected by ELISA. The serum concentrations of IL-7 and IL-15 in patients with KD were significantly lower compared with the concentrations in the healthy controls and the KD patients after IVIG therapy (P < 0.05). And the IFN-γ concentration in KD was higher compared with the concentration in the healthy controls and the KD patients after IVIG therapy (P < 0.05). But there were no obvious difference to be found between the patients with KD and the healthy controls in concentrations of IL-12 and TGF-β (P > 0.05) (shown in Table 4). NKG2A is an inhibitory receptor expressed on NK cells and CD8+T cells.

Lactoferrin, a component of

breast milk and genital secretions, has also been shown to inhibit HIV-1 Sirolimus replication and transmission from dendritic cells (DCs) to T cells in vitro[70–72]. Nevertheless, cervicovaginal levels of lactoferrin, RANTES and SLP1 were tested in HIV-1 seronegative women at a high risk of heterosexual acquisition of HIV infection and were found to be associated with bacterial vaginosis and inflammation rather than exposure to HIV-1 [73]. In contrast, elafin/trappin-2 was found to be elevated in the female genital tract of HESN Kenyan sex workers and was associated with protection against HIV-1 acquisition [74]. Defensins represent a family of small cationic peptides expressed in the mucosal epithelium with broad anti-microbial properties against HIV-1 and other sexually transmitted diseases relevant to HIV-1 transmission [75]. Both α-defensins and Bioactive Compound Library β-defensins have been associated repeatedly with

protection in several independent studies of HESN subjects [76–80]. This includes the description of alpha-defensins in the prevention of HIV transmission among breastfed infants [76] and the identification of elevated levels of both alpha and beta-defensins in sexually HIV-1 exposed but uninfected individuals [79,80]. Despite potent HIV inhibitory activity, however, cervicovaginal levels of α-defensins have also been associated with increased HIV acquisition due to their association with bacterial sexually transmitted infections [81]. The role of α-defensins in HIV-1 vertical transmission remains contentious, with one study showing no association between α-defensin concentration in breast milk and risk of HIV-1 transmission [82] while another study showed the opposite [76]. Overall, the varied secreted proteins identified in the mucosa of HESN subjects (summarized in Table 2) may represent true factors associated with reducing

mucosal transmission of HIV-1 infection. Rather, they may reflect the innate immune response to genital tract inflammation due to ongoing bacterial infections or sexually transmitted diseases, which may be endemic in the case of sex worker mafosfamide cohorts. Taking the data as a whole, we interpret that soluble innate factors are likely to modulate the infectivity threshold for HIV-1 upon exposure. However, secreted anti-viral factors alone are unlikely to render a complete barrier to infection, and innate immune cells such as natural killer (NK) cells and DCs may also bolster the threshold to infection that HIV-1 must overcome. NK cells represent a critical component of the host innate immune response against viral infection and serve as a front-line defence against a diverse array of pathogens.

Sjögren’s syndrome (SS) is an autoimmune disease that affects primarily the salivary and lachrymal glands, causing xerostomia and

so-called ‘Sicca syndrome’, and is categorized thus as an organ-specific autoimmune disease. The pathogenetic mechanisms consist of an autoimmune LY294002 molecular weight process leading to the progressive destruction of salivary and lachrymal glands. Therefore, symptoms of SS are chronic and sometimes irreversible. It is well known that autoimmune diseases often overlap with other collagen diseases, and this is also the case for SS. Without overlapping with any other autoimmune diseases, SS is called primary SS, while SS that overlaps with other autoimmune diseases is termed secondary SS. It has been reported that approximately half of SS cases are secondary SS [1]. SS can be seen alone (primary SS) or in association with other autoimmune rheumatic disease, especially rheumatoid arthritis (RA), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) (secondary

SS). It has not been explained clearly why SS is prone to merge with these autoimmune diseases. Although the essential mechanism of autoimmune diseases is still largely unknown, Daporinad various immune cells are suggested to be involved in their genesis. Among those immune cells, dendritic cells (DCs) have emerged recently as candidates for the master cells that elicit aberrant immune reactions in autoimmune diseases [2–7]. DCs are professional antigen-presenting cells (APCs) that have a unique capacity to prime naive T cells and induce them to develop into effector T cells. Thus, DCs are regarded as being the master regulators of adaptive immune responses. Furthermore, recent progress of DC biology has highlighted the functional plasticity of DCs; DCs can induce not only inflammatory immune responses but also peripheral tolerance, depending upon their subsets, the maturation stage of DCs and microenvironments such as cytokine milieu or stimuli [8,9]. These biological properties of DCs may lead to a

hypothesis that functional alteration of the DC system causes development of autoimmune diseases. Human peripheral blood contains Ketotifen two major subsets of DCs: CD11c+ myeloid DCs and plasmacytoid DCs [10,11]. Blood myeloid DCs are in the immature stage and seem to be en route to peripheral and lymphoid tissues; they may contribute mainly to T helper type 1 (Th1)-mediated adaptive immune responses by producing interleukin (IL)-12 in response to microbial pathogens. On the other hand, blood plasmacytoid DCs are identical to circulating natural type 1 interferon (IFN)-producing cells, which may contribute to anti-viral innate immunity. The analysis of blood DCs may provide a novel and unique perspective in dissecting the pathogenesis of autoimmune diseases. There is evidence that mature DCs infiltrated into the RA joint mediate immunopathology in RA [3,4].

This work was supported by the VA Merit Program and Medical Research Service, by U.S. Department of Veterans Affairs and by Grant RO1-AI-36680 from the National Institutes of Health. Figure S1 (S1): Panel S1-D: Phenotype of mouse BMDCs

activated by C. parvum antigen(s) stimulation. Whole BM was cultured in vitro and DCs were harvested at day 11. selleck chemicals llc Cell surface expression of co stimulatory markers CD86 (S1-A), CD40 (S1-B), MHC class II (S1-C) and CD209 (DC-SIGN) (S1-D) were evaluated in unstimulated MoDCs or DCs stimulated for 18hrs with soluble antigen, live sporozoites, LPS and recombinant antigens Cp40, Cp23, Cp17 and P2. Expression of the indicated markers is shown

by the histograms, each panel has its own isotype control. Values represent percentage of cells staining positive for that marker. Data are representative from one of three experiments. “
“Despite curative locoregional treatments for hepatocellular carcinoma (HCC), tumour recurrence rates remain high. The current study was designed to assess the safety and bioactivity of infusion of dendritic cells (DCs) stimulated with OK432, a streptococcus-derived anti-cancer immunotherapeutic agent, into tumour tissues following transcatheter hepatic arterial embolization learn more (TAE) treatment in patients with HCC. DCs were derived from peripheral blood monocytes of patients with hepatitis C virus-related cirrhosis and HCC in the presence of interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor and stimulated with 0·1 KE/ml OK432 for 2 days. Thirteen patients were administered with 5 × 106

of DCs through arterial catheter during the procedures of TAE treatment on day 7. The immunomodulatory effects and clinical responses were evaluated in comparison with a group of 22 historical controls treated Fossariinae with TAE but without DC transfer. OK432 stimulation of immature DCs promoted their maturation towards cells with activated phenotypes, high expression of a homing receptor, fairly well-preserved phagocytic capacity, greatly enhanced cytokine production and effective tumoricidal activity. Administration of OK432-stimulated DCs to patients was found to be feasible and safe. Kaplan–Meier analysis revealed prolonged recurrence-free survival of patients treated in this manner compared with the historical controls (P = 0·046, log-rank test). The bioactivity of the transferred DCs was reflected in higher serum concentrations of the cytokines IL-9, IL-15 and tumour necrosis factor-α and the chemokines CCL4 and CCL11. Collectively, this study suggests that a DC-based, active immunotherapeutic strategy in combination with locoregional treatments exerts beneficial anti-tumour effects against liver cancer.

In the Atm−/− mouse model of ataxia-telengiectasia, the variation in intestinal microbiota due to either differences in the environments of various animal find more facilities or to experimentally induced modifications was shown to profoundly modify lymphoma incidence and

survival of the mice [164]. The intestinal microbiota appears to affect carcinogenesis in distant organs, in part by modulating the tumor necrosis factor (TNF) dependent systemic inflammatory tone, oxidative stress, and leukocyte or epithelial cell genotoxicity [161, 162, 164, 165]. Dysbiosis or antibiotics treatment could alter the ability of the microbiota to metabolize estrogens, an activity that has been inferred to be a possible noninflammatory

mechanism by which the microbiota modulates distant malignancies [137]. However, unlike the induction of mammary carcinoma in APCmin/+/Rag2−/− mice by H. hepaticus, the evidence for an association between antibiotics usage and breast cancer in humans remains tenuous [166]. Recently, it has also been shown in mice that the overgrowth of fungal Candida species due to antibiotics treatment-driven gut dysbiosis GSK2118436 supplier increases plasma prostaglandin E2 concentrations and M2 macrophage polarization in the lung [41]. Although this effect of antibiotics treatment has been evaluated in terms of induction of allergic airway inflammation [41], one may speculate that the induction of tumor-promoting M2 macrophages indirectly via antibiotics treatment may also play a role in tumor progression. In recent murine studies, the gut microbiota has been shown to affect the response to both immune and chemotherapy by regulating different myeloid-derived cell functions in the tumor microenvironment. Intratumoral CpG-oligodeoxynucleotides (ODN) immunotherapy Niclosamide combined with antibody neutralization of IL-10 signaling effectively

treats sterile transplanted subcutaneous tumors in conventional mice, but not in GF or antibiotic-treated mice [22]. This treatment induces, within hours, extensive hemorrhagic tumor necrosis that is dependent on TNF and NO production by tumor-associated innate myeloid cells, followed by CD40-mediated DC activation, IL-12 production, and the generation of a CD8+ T-cell-mediated tumor-specific adaptive immunity required for persistent tumor eradication [167]. In the absence of gut commensal microbiota, however, the tumor-infiltrating myeloid-derived cells recruited after CpG-ODN treatment have impaired production of various inflammatory cytokines, including TNF and IL-12 [22] (Fig. 2).