Macrophage dynamics in prostate cancer: Molecular to therapeutic insights.

This review provides an in-depth examination of the role that tumor-associated macrophages (TAMs) play in the progression of prostate cancer (PCa), with a particular focus on the factors influencing the polarization of M1 and M2 macrophages and the implications of targeting these cells for cancer progression. The development and prognosis of PCa are significantly influenced by the behavior of macrophages within the tumor microenvironment. M1 macrophages typically exhibit anti-tumor properties by secreting pro-inflammatory cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), thereby enhancing the immune response. Conversely, M2 macrophages contribute to tumor cell migration and invasion through the production of factors like arginase-1 (Arg1) and interleukin-10 (IL-10). This review not only explores the diverse factors that affect macrophage polarization but also delves into the potential therapeutic strategies targeting macrophage polarization, including the critical roles of non-coding RNA and exosomes in regulating this process. The polarization state of macrophages is highlighted as a key determinant in PCa progression, offering a novel perspective for clinical treatment. Future research should concentrate on gaining a deeper understanding of the molecular mechanisms underlying macrophage polarization and on developing effective targeted therapeutic strategies. The exploration of the potential of combination therapies to improve treatment efficacy is also emphasized. By emphasizing the importance of macrophages as a therapeutic target in PCa, this review aims to provide valuable insights and research directions for clinicians and researchers.

Visual Electrofluorochromic Detection of Cancer Cell Surface Glycoprotein on a Closed Bipolar Electrode Chip.

This work reports an electrofluorochromic strategy on the basis of electric field control of fluorescent signal generation on bipolar electrodes (BPEs) for visualizing cancer cell surface glycoprotein (mucin 1). The device included two separate cells: anodic sensing cell and cathodic reporting cell, which were connected by a screen-printing electrode patterned on poly(ethylene terephthalate) (PET) membrane. In the sensing cell, anti-MUC1 antibody immobilized on a chitosan-multiwalled carbon nanotube (CS-MWCNT)-modified anodic BPE channel was used for capturing mucin-1 (MUC1) or MCF-7 cancer cells. Then ferrocene (Fc)-labeled mucin 1 aptamers were introduced through hybridization. Under an applied voltage, the ferrocene was oxidized and the electroactive molecules of 1,4-benzoquinone (BQ) in the cathodic reporting cell were reduced according to electroneutrality. This produced a strongly basic 1,4-benzoquinone anion radical (BQ•-), which turned on the fluorescence of pH-responsive fluorescent molecules of (2-(2-(4-hydroxystyryl)-6-methyl-4 H-pyran-4-ylidene)malononitrile) (SPM) coexisting in the cathode reporting cell for both spectrophotometric detection and imaging. This strategy allowed sensitive detection of MUC1 at a concentration down to 10 fM and was capable of detecting a minimum of three MCF-7 cells. Furthermore, the amount of MUC1 on MCF-7 cells was calculated to be 6.02 × 104 molecules/cell. Our strategy also had the advantages of high temporal and spatial resolution, short response time, and high luminous contrast and is of great significance for human health and the promotion of life science development.

Simultaneous detection of three biomarkers related to acute myocardial infarction based on immunosensing biochip.

An immunosensing biochip for simultaneous detection of three biomarkers related to acute myocardial infarction (AMI) was developed based on anionic soybean peroxidase (SBP) functionalized nanoprobe and chemiluminescent imaging. The nanoprobes (Ab2-SiO2-SBP) were fabricated by co-immobilization of SBP and one of the detection polyclonal antibodies, anti-cardiac troponin I antigen (anti-cTnI), anti-creatine kinase-MB (anti-CK-MB) and anti-myoglobin (anti-Myo), on the silica nanoparticle surface. The detection sensitivity was enhanced since the large surface area of silica carriers increased the loading of SBP for per sandwiched immunoreaction. The immunosensing biochip designed as 3 × 8 wells array was constructed by simultaneously immobilizing three capture monoclonal antibodies on the same one microtiter well with 2 × 3 active spots. In the presence of target protein, the nanoprobes will be attached onto the spots with high specificity through the sandwiched immunoreactions, which triggered the chemiluminescence (CL) signals on each sensing site of the microtiter plates and allowed to CL imaging of three biomarkers in one well at the same time. Therefore, the proposed biochip was a promising convenient strategy for simultaneous detection of cTnI, CK-MB and Myo, which showed potential application for multianalyte determination in clinical diagnostics.

Electrochemiluminescent detection of cardiac troponin I by using soybean peroxidase labeled-antibody as signal amplifier.

This work proposed an electrochemiluminescence (ECL) immunosensor for quantitative monitoring of cardiac troponin I (cTnI) in plasma with soybean peroxidase (SBP) labeled-antibody as signal amplifier. The ECL sandwich immunosensor was constructed by covalent binding anti-cTnI capture antibody (Ab1) to polyethylenimine-functionalized graphene matrix, which was obtained by a simple hydrothermal reaction between polyethylenimine (PEI) and graphene oxide (GO). After that, the SBP-labeled detection antibody (SBP-Ab2), synthesized by NaIO4 method, was immobilized on the surface of electrode through sandwich immunoreaction. The SBP on electrode surface displayed strong and stable ECL signal of luminol in the presence of H2O2, which could be used for cTnI detection with a concentration range of 5-30,000pg/mL and a detection limit of 3.3pg/mL. This proposed SBP-modified immunosensor displayed high sensitivity, selectivity and accuracy, and was expected not only to detect cTnI in practical human plasma sample but also to be used in other biomarkers detection.

High Seroprevalence of Human Herpesvirus 8 Infection in HIV-positive Homosexual Men in Jiangsu Province, China.

BACKGROUND: HIV-infected homosexual men are more frequently diagnosed with Kaposi's sarcoma. With the increase of HIV-infected homosexual men in China, we urgently need to know the KS-related human herpesvirus (KSHV/HHV-8) seroprevalence in this population. To investigate HHV-8 prevalence among HIV-positive homosexual men, we recruited 183 patients naive of antiretroviral therapy (ART) whose blood samples presented with HIV-antibody positive as confirmed by western blot. METHODS: HIV viral load was tested using Cobas TaqMan HIV-1 test Version 2.0, and CD4 T cell counts were tested using a Flow cytometry instrument. All HIV-positive blood samples were collected and screened for KSHV. Immunofluorescence (IFA) test was conducted for HHV-8-Specific antibodies (anti-LANA) in the plasma. HHV-8 DNA in whole blood cells of IFA-positive subjects was quantified with Real-time polymerase chain reaction (RT-PCR). RESULTS: All samples showed HIV RNA positive. CD4+ T cell count was 23% cases (42/183) which showed ≤200 cells/µL, 51.3% cases (94/183) showed 201-500 cells/µL and 25.7% cases (47/183) showed ≥501 cells/µL. Immunofluorescence (IFA) test demonstrated an HHV-8 prevalence of 50.8% (93/183), among which 20.4% of the cases (19/93) were HHV-8 DNA positive. HHV-8 infection showed no difference among different age groups (p=0.96). Similarly, HHV-8 infection exhibited no significant difference among different HIV viral load groups (p=0.08). However, HHV-8 infection among different CD4+ T cell count showed significant difference (P=0.0004). CONCLUSION: This study showed a high seroprevalence of human herpesvirus 8 infection in HIVpositive homosexual men.

Microbial HSP70 peptide epitope 407-426 as adjuvant in tumor-derived autophagosome vaccine therapy of mouse lung cancer.

Tumor-derived autophagome (DRibble) is an effective therapeutic cancer vaccine inducing T cell recognition and death of tumor cells in mice. However, the potential for improved anti-tumor response still remains. Our previous study demonstrated that two repeats of a mycobacterial HSP70407-426 (M2) peptide acted as adjuvant in improving anti-tumor efficacy of human umbilical vein endothelial cell (HUVEC) vaccine. Here, a DRibble vaccine conjugated with M2 (DRibble-M2) was designed as a novel vaccine to enhance anti-tumor activity. Compared with DRibble alone, DRibble-M2 vaccination more significantly inhibited the growth of mouse Lewis lung cancer both in a subcutaneous tumor model and in a lung metastasis model. Higher expression of antigen-specific CTL was induced by DRibble-M2. DRibble-M2 induced higher CD83 and CD86 expression in DC2.4 and also improved the internalization of DRibble antigen into DC2.4. Our data indicated that DRibble-M2 is a potential vaccine for clinical cancer therapy.

Circulating human cytomegalovirus-encoded HCMV-miR-US4-1 as an indicator for predicting the efficacy of IFNα treatment in chronic hepatitis B patients.

The efficacy of interferon α (IFNα) therapy for chronic hepatitis B (CHB) patients is about 40% and often associates with adverse side-effects, thus identification of an easy accessible biomarker that can predict the outcome of IFNα treatment for individual CHB patients would be greatly helpful. Recent reports by us and others show that microRNAs encoded by human cytomegalovirus (HCMV) were readily detected in human serum and can interfere with lymphocyte responses required by IFNα therapeutic effect. We thus postulate that differential expression profile of serum HCMV miRNAs in CHB patients may serve as indicator to predict the efficacy of IFNα treatment for CHB patients. Blood was drawn from 56 individual CHB patients prior to IFNα treatment. By quantifying 13 HCMV miRNAs in serum samples, we found that the levels of HCMV-miR-US4-1 and HCMV-miR-UL-148D were significantly higher in IFNα-responsive group than in IFNα-non-responsive group. In a prospective study of 96 new CHB patients, serum level of HCMV-miR-US4-1 alone classified those who were and were not responsive to IFN-α treatment with correct rate of 84.00% and 71.74%, respectively. In conclusion, our results demonstrate that serum HCMV-miR-US4-1 can serve as a novel biomarker for predicting the outcome of IFNα treatment in CHB patients.

Augmented CD3(+)CD8(+) and CD3(+)CD56(-) cells in cytokine-induced killer cells cultured with engineered cells for costimulatory enhancement from heavily pretreated patients with solid tumor.

BACKGROUND AIMS: Cytokine-induced killer cells (CIKs) were shown to be a promising tool in the quest for new therapeutic approaches in the setting of metastatic solid tumors refractory to standard treatments. However, there is a practical clinical problem of different expansion rates and cell function as individual variability exists. Stimulatory molecular 4-1BB could promote division and survival of T cells and enhance effector activity including cytokine production. This study aimed to invest the contribution of co-stimulation signal to CIKs production for exploring new strategies, which increase the expansion and reliability of CIKs generation to improve access to CIKs therapy. METHODS: We studied the larger-scale expansion of CIKs cultured with engineered cells for costimulatory enhancement (ECCE) consisting of K562 cells that expressed 4-1BBL in heavily pretreated patients with solid tumor. The proliferation and cytotoxic capacity of CIKs were evaluated. Phenotypes of CIKs were analyzed using flow cytometry. Cytokine levels of interferon (IFN)-γ and tumor necrosis factor (TNF)-α were detected using enzyme-linked immunosorbent assay (ELISA). RESULTS: The proliferation and cytotoxic activity of CIKs were significantly up-regulated by ECCE. The percentages of CD3(+)CD8(+) and CD3(+)CD56(-) CIKs were significantly increased while the percentage of CD3(+)CD56(+) CIKs was decreased. In addition, the secretion of IFN-γ and TNF-α by CIKs could also be enhanced significantly when ECCE were added into the culture system. CONCLUSIONS: This study suggests that ECCE may improve the efficacy of CIKs therapy and make CIKs therapy possible for the patients whose CIKs would be hard to be cultured using conventional methods.

Colorimetric detection of influenza A virus using antibody-functionalized gold nanoparticles.

Early and accurate diagnosis is considered the key issue to prevent the further spread of viruses and facilitate influenza therapy. Herein, we report a colorimetric immunosensor for influenza A virus (IAV) based on gold nanoparticles (AuNPs) modified with monoclonal anti-hemagglutinin antibody (mAb). The immunosensor allows for a fast, simple, and selective detection of IAV. In this assay, influenza-specific antibodies are conjugated to AuNPs to create mAb-AuNP probes. Since IAV has multiple recognition sites for probes on the surface, the mAb-AuNP probes can be specifically arranged on the virus surface due to their very specific antigen recognition. In this case, this aggregation of the mAb-AuNP probes produces a red shift in the absorption spectrum due to plasmon coupling between adjacent AuNPs, and it can be detected with the naked eye as a color change from red to purple and quantified with the absorption spectral measurements. The aggregate formation is also confirmed with transmission electron microscopy (TEM) imaging and dynamic light scattering (DLS). Under the optimal conditions, the present immunoassay can sensitively measure H3N2 IAV (A/Brisbane/10/2007) with a detection limit of 7.8 hemagglutination units (HAU). This proposed immunosensor revealed high specificity, accuracy, and good stability. Notably, it is a single-step detection using AuNP probes and UV-vis spectrophotometer for readout, and no additional amplification, e.g., enzymatic, is needed to read the result. This assay depends on an ordered AuNP structure covering the virus surface and can be applied to any virus pathogen by incorporating the appropriate pathogen-specific antibody.

Prediction of antiviral efficacy in patients with chronic hepatitis C by changes in forkhead box protein 3 levels.

The aim of the present study was to investigate the distribution of CD4+CD25+ regulatory T cells (Tregs) in the peripheral blood of patients with chronic hepatitis C; in addition to identifying whether the distribution of CD4+CD25+ Tregs predicts the efficacy of antiviral therapy for HCV. The expression of CD4+CD25+ forkhead box protein (FOXP) 3+ Tregs within a CD4+ T cell population was detected in the peripheral blood obtained from patients with chronic hepatitis C and from healthy control subjects using flow cytometry. The hepatitis C virus (HCV)-RNA load was measured using quantitative-fluorescence polymerase chain reaction. CD4+CD25+FOXP3+ Tregs accounted for 14.24±1.33% of the CD4+ T cells in the peripheral blood of patients with chronic hepatitis C, which was higher than that of the healthy control subjects (5.62±1.21%; P<0.001). Furthermore, the frequency of CD4+CD25+FOXP3+ Tregs in CD4+ T cells of the peripheral blood positively correlated with the HCV-RNA load (r=0.73; P=0.032). Therefore, the results of the present study indicated that the expression of CD4+CD25+FOXP3+ Tregs increased in patients that were chronically infected with HCV and positively correlated with the HCV-RNA load.

Genetic variants in human leukocyte antigen-DP influence both hepatitis C virus persistence and hepatitis C virus F protein generation in the Chinese Han population.

Chronic hepatitis C is a serious liver disease that often results in cirrhosis or hepatocellular carcinoma. The aim of this study was to assess the association of human leukocyte antigen-DP (HLA-DP) variants with risk of chronic hepatitis C virus (HCV) or anti-F antibody generation. We selected two single nucleotide polymorphisms (SNPs) in a region including HLA-DPA1 (rs3077) and HLA-DPB1 (rs9277534) and genotyped SNPs in 702 cases and 342 healthy controls from the Chinese population using TaqMan SNP genotyping assay. Moreover, the exon 2 of the HLA-DPA1 and HLA-DPB1 genes were amplified and determined by sequencing-based typing (SBT). The results showed that rs3077 significantly increased the risk of chronic HCV infection in additive models and dominant models (odds ratio (OR) = 1.32 and 1.53). The rs3077 also contributed to decrease the risk of anti-F antibody generation in additive models and dominant models (OR = 0.46 and 0.56). Subsequent analyses revealed the risk haplotypes (DPA1*0103-DPB1*0501 and DPA1*0103-DPB1*0201) and protective haplotypes (DPA1*0202-DPB1*0501 and DPA1*0202-DPB1*0202) to chronic HCV infection. Moreover, we also found that the haplotype of DPA1*0103-DPB1*0201 and DPA1*0202-DPB1*0202 were associated with the anti-F antibody generation. Our findings show that genetic variants in HLA-DP gene are associated with chronic HCV infection and anti-F antibody generation.

Electrochemiluminescence resonance energy transfer between graphene quantum dots and gold nanoparticles for DNA damage detection.

Bright blue luminescent graphene quantum dots (GQDs) with major graphitic structured nanocrystals and a photoluminescence (PL) quantum yield of 15.5% were synthesized and used to monitor DNA damage. The GQDs were prepared by ultraviolet irradiation without using a chemical agent. The as-prepared GQDs showed excitation-dependent PL and stable electrochemiluminescence (ECL) behaviors. Gold nanoparticles (AuNPs) were linked with a probe of single-stranded DNA (cp53 ssDNA) to form AuNPs-ssDNA. The ECL signal of the GQDs could be quenched by non-covalent binding of the AuNPs-ssDNA to the GQDs, due to the occurrence of an electrochemiluminescence resonance energy transfer between the GQDs and the AuNPs. When AuNPs-ssDNA was then hybridized with target p53 DNA to form AuNPs-dsDNA, the non-covalent interaction between the GQDs and the ds-DNA weakened and the ECL of the GQDs recovered. This engendered an ECL sensor for the detection of target p53 ssDNA, with a detection limit of 13 nM. The resultant ECL sensor could be used for DNA damage detection based on its different bonding ability to damaged target p53 ssDNA and cp53 ssDNA linked AuNPs. The presented method could be expanded to the development of other ECL biosensors, for the quantification of nucleic acids, single nucleotide polymorphisms or other aptamer-specific biomolecules.

Hepatitis C virus alternate reading frame protein decreases interferon-α secretion in peripheral blood mononuclear cells.

The hepatitis C virus (HCV) alternate reading frame protein (ARFP or F protein) of the HCV 1b genotype is a double-frameshift product of the HCV core protein (Core). The discovery of HCV F protein challenges various biological functions attributed to Core. However, the specific characteristics of the host cellular immune response to F protein during HCV infection have yet to be fully elucidated. Therefore, the present study investigated the cytokine response to HCV Core or F protein in peripheral blood mononuclear cells (PBMCs) and plasmacytoid dendritic cells (PDCs) from patients with chronic HCV and healthy donors in vitro. The results demonstrated that the levels of interferon (IFN)-α, analyzed by an enzyme-linked immunosorbent assay, secreted by PBMCs in patients positive for the anti-F protein antibody, were lower than those of patients negative for the anti-F protein antibody. Moreover, the frequency of PDCs in patients negative for the anti-F protein antibody, were higher than in the group positive for the anti-F protein antibody. Furthermore, HCV F protein and Core not only inhibited specific unmethylated CpG oligonucleotide sequences of type A (CpG­A)-induced IFN-α production by PBMCs and PDCs, but also upregulated the production of interleukin (IL)-10 by PBMCs in patients with chronic HCV and healthy controls. Notably, following neutralization of IL-10 in the media and in vitro Core or F protein stimulation, levels of IFN-α were increased. Moreover, the results revealed that the roles of F protein and Core were similar with regard to the induction of apoptosis of PDCs in patients with chronic HCV. These findings suggest that F protein may inhibit PBMC IFN-α secretion by regulating the production of IL-10, and may contribute to an increase in the rates of apoptosis in PDCs. In conclusion, the results have revealed a potential involvement of F protein in the mechanisms of chronic hepatitis C.

Detection of DNA damage by thiazole orange fluorescence probe assisted with exonuclease III.

This work reports a fluorescent dye insertion approach for detection of DNA damage. The capture DNA with overhanging 3'-terminus was immobilized on silicon surface to hybridize with target DNA. The intercalation of cyanine dye of thiazole orange (TO) to the double helix structure of DNA (dsDNA) allowed intense enhancement of fluorescence signal. The DNA damage with chemicals led to poor intercalation of TO into double helix structure, resulting in the decrease of the fluorescence signal. This signal decrease could be further enhanced by exonuclease III (Exo III). With this approach, the target DNA could be detected down to 47 fM. Seven chemicals were chosen as models to monitor DNA damage. The results suggested that the present strategy could be developed to detect DNA damage, to classify the damaging mechanism with chemicals and to estimate the toxic effect of chemicals.

Hepatitis E virus genotype 4, Nanjing, China, 2001-2011.

During 2001-2011, hepatitis E virus (HEV) was found in the blood of patients in Nanjing, China. All HEV-positive patients had virus genotype 4; subgenotype 4a was predominant. The effective population of HEV in Nanjing increased in ≈1980 and continued until ≈2003 when it plateaued.

Selective collection and detection of MCF-7 breast cancer cells using aptamer-functionalized magnetic beads and quantum dots based nano-bio-probes.

A novel strategy for selective collection and detection of breast cancer cells (MCF-7) based on aptamer-cell interaction was developed. Mucin 1 protein (MUC1) aptamer (Apt1) was covalently conjugated to magnetic beads to capture MCF-7 cell through affinity interaction between Apt1 and MUC1 protein that overexpressed on the surface of MCF-7 cells. Meanwhile, a nano-bio-probe was constructed by coupling of nucleolin aptamer AS1411 (Apt2) to CdTe quantum dots (QDs) which were homogeneously coated on the surfaces of monodispersed silica nanoparticles (SiO2 NPs). The nano-bio-probe displayed similar optical and electrochemical performances to free CdTe QDs, and remained high affinity to nucleolin overexpressed cells through the interaction between AS1411 and nucleolin protein. Photoluminescence (PL) and square-wave voltammetric (SWV) assays were used to quantitatively detect MCF-7 cells. Improved selectivity was obtained by using these two aptamers together as recognition elements simultaneously, compared to using any single aptamer. Based on the signal amplification of QDs coated silica nanoparticles (QDs/SiO2), the detection sensitivity was enhanced and a detection limit of 201 and 85 cells mL(-1) by PL and SWV method were achieved, respectively. The proposed strategy could be extended to detect other cells, and showed potential applications in cell imaging and drug delivery.

Anti-tumor efficacy of a hepatocellular carcinoma vaccine based on dendritic cells combined with tumor-derived autophagosomes in murine models.

The majority of hepatocellular carcinoma (HCC) patients have a poor prognosis with current therapies, and new approaches are urgently needed. We have developed a novel therapeutic cancer vaccine platform based on tumor cell derived autophagosomes (DRibbles) for cancer immunotherapy. We here evaluated the effectiveness of DRibbles-pulsed dendritic cell (DC) immunization to induce anti-tumor immunity in BALB/c mouse HCC and humanized HCC mouse models generated by transplantation of human HCC cells (HepG2) into BALB/c-nu mice. DRibbles were enriched from H22 or BNL cells, BALB/c-derived HCC cell lines, by inducing autophagy and blocking protein degradation. DRibbles-pulsed DC immunization induced a specific T cell response against HCC and resulted in significant inhibition of tumor growth compared to mice treated with DCs alone. Anti- tumor efficacy of the DCs-DRibbles vaccine was also demonstrated in a humanized HCC mouse model. The results indicated that HCC/DRibbles-pulsed DCs immunotherapy might be useful for suppressing the growth of residual tumors after primary therapy of human HCC.

Th1 and Th2 cytokine profiles induced by hepatitis C virus F protein in peripheral blood mononuclear cells from chronic hepatitis C patients.

Th1 and Th2 cytokine response has been confirmed to be correlated with the pathogenesis of HCV infection. The aim of the study is to investigate the Th1 and Th2 cytokine profiles induced by HCV alternate reading frame protein (F protein) in chronic hepatitis C patients. We assessed the immune responses specific to HCV F protein in 55 chronic HCV patients. IFN-γ, IL-2, IL-4 and IL-5 secretion by peripheral blood mononuclear cells (PBMC) post F protein stimulation were compared among HCV patients and healthy donors. Finally, the associations between HCV F protein and HLA class II alleles were explored. We found that the seroprevalence of anti-F antibodies in HCV-related hepatocellular carcinoma (HCC) patients was significantly higher than that of patients without HCC, but such a significant difference in humoral immune responses to F protein was not observed in HCV 1b-infected- and non-HCV 1b-infected-patients. Additionally, the PBMC proliferation of HCC patients was significantly lower than that of patients without HCC. Furthermore, F protein stimulation of PBMCs from F-seropositive patients resulted in Th2 biased cytokine responses (significantly decreased IFN-γ and/or IL-2 and significantly increased IL-4 and/or IL-5 levels) that reportedly may contribute to HCC progression and pathogenesis. However, no significant difference in the association between HCV F protein and HLA-DRB1*0201, 0301, 0405, 1001 and HLA-DQB1*0201, 0401, 0502, 0602 was observed in this study. These findings suggest that F protein may contribute to the HCV-associated bias in Th1/Th2 responses of chronic hepatitis C patients including the progress of HCC pathogenesis.

Microbial TLR Agonists and Humoral Immunopathogenesis in HIV Disease.

Although T cells are the primary and most-studied targets of the Human Immunodeficiency Virus (HIV), B cells, especially memory B lymphocytes, are also chronically depleted in the course of HIV disease. Although the lack of CD4+ T cell help may explain these deficiencies, intrinsic defects in B lymphocytes appear to contribute to B cell depletion and reduced antibody (Ab) production in the setting of HIV, especially of some antigens eliciting T cell-independent responses. The gut mucosal barrier is disrupted in HIV disease, resulting in increased systemic exposure to microbial products such as Toll-Like Receptor (TLR) agonists. The association of enhanced systemic levels of TLR agonists and B cell dysfunction in HIV disease is not understood. This review discusses the potential role of microbial TLR agonists in the B cell depletion, enhanced autoantibody production and impaired responses to vaccination observed in HIV-infected hosts. Increased microbial translocation in HIV infection may drive B cells to produce autoantibodies and increase susceptibilities of B cells to apoptosis through activation-induced cell death. Determining the mechanisms of B cell perturbations in HIV disease will inform the design of novel strategies of improve immune responses to vaccines, reduce opportunistic infections and slow disease progression.

Autophagy-assisted antigen cross-presentation: Autophagosome as the argo of shared tumor-specific antigens and DAMPs.

It is generally believed that most tumor antigens are passively released from either health or dying tumor cells as intact soluble antigens, peptide fragments complexed with heat shock proteins (HSPs), or packaged in secretary vesicles in the form of microparticles or exosomes. The passive release of tumor antigens is generally non-inflammatory and non-immunogenic; however, results from others and our laboratories suggest that autophagy is critically involved in immunogenic cell death.