Development of dendritic cell loaded MAGE-A2 long peptide; a potential target for tumor-specific T cell-mediated prostate cancer immunotherapy.

BACKGROUND: Prostate cancer (PCa) is the second leading cause of cancer-related deaths among men worldwide. Immunotherapy is an emerging treatment modality for cancers that harnesses the immune system's ability to eliminate tumor cells. In particular, dendritic cell (DC) vaccines, have demonstrated promise in eliciting a tumor-specific immune response. In this study, we investigated the potential of using DCs loaded with the MAGE-A2 long peptide to activate T cell cytotoxicity toward PCa cell lines. METHODS: Here, we generated DCs from monocytes and thoroughly characterized their phenotypic and functional properties. Then, DCs were pulsed with MAGE-A2 long peptide (LP) as an antigen source, and monitored for their transition from immature to mature DCs by assessing the expression levels of several costimulatory and maturation molecules like CD14, HLA-DR, CD40, CD11c, CD80, CD83, CD86, and CCR7. Furthermore, the ability of MAGE-A2 -LP pulsed DCs to stimulate T cell proliferation in a mixed lymphocyte reaction (MLR) setting and induction of cytotoxic T cells (CTLs) in coculture with autologous T cells were examined. Finally, CTLs were evaluated for their capacity to produce interferon-gamma (IFN-γ) and kill PCa cell lines (PC3 and LNCaP). RESULTS: The results demonstrated that the antigen-pulsed DCs exhibited a strong ability to stimulate the expansion of T cells. Moreover, the induced CTLs displayed substantial cytotoxicity against the target cells and exhibited increased IFN-γ production during activation compared to the controls. CONCLUSIONS: Overall, this innovative approach proved efficacious in targeting PCa cell lines, showcasing its potential as a foundation for the development and improved PCa cancer immunotherapy.

The prospect of targeting T cell immunoglobulin and mucin-domain containing-3 in renal cell carcinoma immunotherapy.

Despite the advances in the diagnosis and treatment of renal cell carcinoma (RCC), it remains one of the most deadly urological cancers. At present, using immune checkpoint inhibition and their combination with antiangiogenic therapy is the standard of care in patients with advanced RCC. Unfortunately, a considerable part of tumour-bearing hosts does not benefit from this type of treatment. However, our knowledge about the detailed role of mucin-domain containing-3 (TIM-3) in the RCC cells is little, and further studies are required in this field, but its significant expression in the RCC microenvironment makes this receptor a promising target for designing new monoclonal antibodies alone or in combination with other checkpoint inhibitors for RCC immunotherapy.

Evaluation of G2013 (α-L-guluronic acid) efficacy on PC-3 cells through inhibiting the expression of inflammatory factors.

Given multiple treatment strategies for prostate cancer, its mortality rate is still high; therefore, novel treatment strategies seem necessary. G2013 or α-L-guluronic acid is a new patented drug with immunomodulatory and anti-inflammatory properties. This study aimed to evaluate the property of G2013 on inflammatory molecules involved in tumorigenesis of prostate cancer. MTT assay was used to assess the effect of the drug on the proliferation of PC-3 cells. Expression of interleukin 8 (IL-8), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), myeloid differentiation factor 88 (MYD-88), cyclooxygenase 2 (COX-2), matrix metalloproteinase-2 (MMP-2), and MMP-9 genes were studied in the PC-3 cells treated with 25 (low dose) or 50 (high dose) µg/mL of G2013 for 24 h using quantitative real-time polymerase chain reaction (qRT-PCR) technique. Protein expression of NF-κB and protein activities of MMP-2 and MMP-9 were assayed using flow cytometry and gelatin zymography, respectively. The expression of COX-2 (p = 0.007 at low dose), MMP-2 (p = 0.023 at low dose, p = 0.002 at high dose), NF-κB (p = 0.004 at low dose) and IL-8 (p < 0.0001 in both doses) genes, NF-κB protein (p < 0.0001 in both doses), and MMP-2 activity (p < 0.0001 in both doses) were significantly reduced in the presence of G2013 as compared to the control group. Cancer cell proliferation was also inhibited under 10-500 µg/mL G2013 treatment. Our results revealed that G2013 has the potential to inhibit PC-3 cell proliferation and reduce the expression of tumour-promoting mediators, COX-2, MMP-2, NF-κB, and IL-8 involved in the progression and metastasis of prostate cancer.

Efficacy of immunotherapy in obese patients with cancer.

Obesity is a condition of excessive fat tissue and high body mass index (BMI ≥30), which is increasing worldwide. Excess body weight is associated with poorer results in cancer treatments; however, recent studies emphasized that elevated BMI was associated with improved outcomes in cases treated by immune checkpoint inhibitor (ICI) therapies, which is called the obesity paradox. In this review, we discuss the correlation between obesity and cancer immunotherapy, especially ICIs, the underlying mechanisms, and the outcomes in different types of cancers. In addition, we describe the occurrence of immune-related adverse events and the effect of gender in obese patients during immunotherapy using all relevant studies with available full texts.

The attentive focus on T cell-mediated autoimmune pathogenesis of psoriasis, lichen planus and vitiligo.

T cell-mediated autoimmune skin diseases develop as a result of the aberrant immune response to the skin cells with T cells playing a central role. These chronic inflammatory skin diseases encompass various types including psoriasis, lichen planus and vitiligo. These diseases show similarities in their immune-pathophysiology. In the last decade, immunomodulating agents have been very successful in the management of these diseases thanks to a better understanding of the pathophysiology. In this review, we will discuss the immunopathogenic mechanisms and highlight the role of T lymphocytes in psoriasis, lichen planus and vitiligo. This study could provide new insights into a better understanding of targeted therapeutic pathways and biological therapies.

Reduced cytoplasmic expression of MAGE-A2 predicts tumor aggressiveness and survival: an immunohistochemical analysis.

BACKGROUND: Melanoma antigen gene A2 (MAGE-A2) is one of the most cancer-testis antigens overexpressed in various types of cancers. Silencing the MAGE-A2 expression inhibited the proliferation of prostate cancer (PCa) cells and increased the chemosensitivity. However, the expression pattern of MAGE-A2 in PCa tissue samples and its prognostic and therapeutic values for PCa patients is still unclear. METHODS: In this study, for the first time, the staining pattern and clinical significance of MAGE-A2 were evaluated in 166 paraffin-embedded prostate tissues, including 148 cases of PCa and 18 cases of high-grade prostatic intraepithelial neoplasia (HPIN), by immunohistochemical analysis. RESULTS: The simultaneous expression of both nuclear and cytoplasmic patterns of MAGE-A2 with different staining intensities was observed among studied cases. Increased expression of MAGE-A2 was significantly found in PCa tissues compared to HPIN cases (P < 0.0001). Among PCa samples, the strong staining intensity of nuclear expression was predominantly observed in comparison with cytoplasmic expression in PCa tissues (P < 0.0001). A significant and inverse correlation was found between the cytoplasmic expression of MAGE-A2 and increased Gleason score (P = 0.002). Increased cytoplasmic expression of MAGE-A2 was associated with longer biochemical recurrence-free survival (BCR-FS) and disease-free survival (DFS) of patients (P = 0.002, P = 0.001, respectively). In multivariate analysis, Gleason score and cytoplasmic expression of MAGE-A2 were independent predictors of the BCR-FS (P = 0.014; P = 0.028, respectively). CONCLUSIONS: Taken together, cytoplasmic expression of MAGE-A2 was inversely proportional to the malignant grade and duration of recurrence of the disease in patients with PCa.

Anti-tumor effect of M2000 (ß-d-mannuronic acid) on the expression of inflammatory molecules in the prostate cancer cell.

Aim: The importance of chronic inflammation during the progression of prostate cancer (PCa) is well-known. M2000 (ß-d-mannuronic acid) is a novel anti-inflammatory drug. According to its potential capacity for the inhibition of molecules involved in creating conditions of inflammation, it is reasonable to assess the anti-inflammatory role of M2000 in PCa cells.Methods: MTT assay was performed to determine the cytotoxicity of M2000 in PC3 cells. Correspondingly, these cells were cultured and then treated with low (25 µg/ml) and high (50 µg/ml) doses of M2000 as optimal doses. Thereafter, real-time RT-PCR, flow cytometry analysis, and zymography were performed to evaluate the expressions of MYD-88, NF-kB, IL-8, COX-2, MMP-2, and MMP-9 molecules. Results: Of note, the M2000 at the concentration of ≤200 µg/ml had no cytotoxicity effect on the cells. MYD-88 gene expression was significantly down-regulated at both low and high doses in the M2000-treated cells compared to the control (p = .017 and p = .001, respectively). The expression of the NF-kB was also reduced at both the gene and protein levels (all p values were <.001). The expression of IL-8 and COX-2 genes was also down-regulated in the high dose of M2000 (p<.001, p = .001, respectively). The decreased expression of the MMP-9 gene was observed at both doses (both p values were <.001).Conclusion: Inhibitory effects of M2000 on the activity of MMPs in the LPS/M2000-treated cells were evident, but not in the M2000-treated cells. M2000 as a new anti-inflammatory drug appears to constitute a potential agent for down-regulation of inflammatory molecules in the PCa cells.

Dendritic cell/cytokine-induced killer cell-based immunotherapy in lung cancer: What we know and future landscape.

Multiple modalities for lung cancer therapy have emerged in the past decade, whereas their clinical applications and survival-beneficiary is little known. Vaccination with dendritic cells (DCs) or DCs/cytokine-induced killer (CIK) cells has shown limited success in the treatment of patients with advanced non-small-cell lung cancer. To evaluate and overcome these limitations in further studies, in the present review, we sum up recent progress about DCs or DCs/CIKs-based approaches for preclinical and clinical trials in patients with lung cancer and discuss some of the limited therapeutic success. Moreover, this review highlights the need to focus future studies on the development of new approaches for successful immunotherapy in patients with lung cancer.

JAK Inhibition as a New Treatment Strategy for Patients with COVID-19.

After the advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the outbreak of coronavirus disease 2019 (COVID-19) commenced across the world. Understanding the Immunopathogenesis of COVID-19 is essential for interrupting viral infectivity and preventing aberrant immune responses before a vaccine can be developed. In this review, we provide the latest insights into the roles of angiotensin-converting enzyme II (ACE2) and Ang II receptor-1 (AT1-R) in this disease. Novel therapeutic strategies, including recombinant ACE2, ACE inhibitors, AT1-R blockers, and Ang 1-7 peptides, may prevent or reduce viruses-induced pulmonary, cardiac, and renal injuries. However, more studies are needed to clarify the efficacy of these therapeutics. Furthermore, considering the common role of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in AT1-R expressed on peripheral tissues and cytokine receptors on the surface of immune cells, potential targeting of this pathway using JAK inhibitors (JAKinibs) is suggested as a promising approach in patients with COVID-19 who are admitted to hospitals. In addition to antiviral therapy, potential ACE2- and AT1-R-inhibiting strategies, and other supportive care, we suggest other potential JAKinibs and novel anti-inflammatory combination therapies that affect the JAK-STAT pathway in patients with COVID-19. Since the combination of MTX and baricitinib leads to outstanding clinical outcomes, the addition of baricitinib to MTX might be a potential strategy.

A review of the effects of the anesthetic gas nitrous oxide on the immune system; a starting point for future experiences.

Nitrous oxide is a common gas used as an anesthetic agent and analgesic medication in operating rooms. The gas inhibits vitamin B12 dependent-methionine synthase, which converts L-homocysteine and 5-methyltetrahydrofolate to L-methionine and tetrahydrofolate, respectively, via a methylation process. The immune system has been frequently reported to be suppressed in anesthetized subjects during the postoperative period. Although previous reviews have focused on the pathophysiologic role of nitrous oxide, none of them has considered the harmful effects of nitrous oxide on the Defense system of the host. In this article, the authors review current studies on the effects of nitrous oxide on the immune system of both patients undergoing surgery and occupational exposure, as well as preclinical studies. Moreover, this paper opens a new horizon for future studies in the context of underlying mechanisms of nitrous oxide actions on the immune system.

Clinical significance of peripheral blood CD11b+/CD33+/HLA-DR- myeloid cells in infants and children with infectious diseases and increased CRP.

Background: At early ages, recurrent or persistent infections are associated with increased serum C-reactive protein (CRP). Inflammatory mediators release inhibitory cells named myeloid-derived suppressor cell (MDSC) into circulating and tumor tissues. In the present study, we assayed the percentage and count of whole blood CD11b+/CD33+/HLA-DR- MDSCs or myeloid cells at early ages with infectious diseases and increased CRP. Methods: In this study, the clinical significance of CD11b+/CD33+/HLA-DR- MDSCs or myeloid cells was evaluated in whole blood samples from 40 patients with infectious disease and 20 healthy controls by flow cytometry analysis. Subsequently, the Pearson correlation between the percentage and absolute count of MDSCs with clinical parameters were obtained by SPSS analysis. A p value of < 0.05 was considered statistically significant. Results: We found a significantly higher level of MDSCs in infants and children with infectious diseases and increased CRP as compared to healthy controls (P=0.003). However, the results of analysis showed no correlation between MDSC percentage and count with grouped age and sex in patient groups. Conclusion: Our findings showed a significant correlation between the high level of serum CRP and peripheral blood CD11b+/CD33+/HLA-DR- MDSCs at early ages. This study could be a roadmap for future studies to use increased CRP as a potential prognostic biomarker to target MDSCs in children with recurrent or persistent infections.

Co-expression of TLR-9 and MMP-13 is associated with the degree of tumour differentiation in prostate cancer.

In vitro experiments demonstrated that stimulation of Toll-like receptor 9 (TLR-9) by synthetic TLR-9 ligands induces the invasion of TLR-9-expressing prostate cancer cells through matrix metalloproteinase 13 (MMP-13). However, the clinical value of TLR-9 and MMP-13 co-expression in the pathophysiology of the prostate is unknown. In the study, we evaluated the expression levels and clinical significance of the TLR-9 and MMP-13 in a series of prostate tissues. One hundred and eighty prostate tissues including prostate cancer (PCa) (n = 137), high-grade prostatic intraepithelial neoplasia (HPIN) (n = 18) and benign prostatic hyperplasia (BPH) (n = 25) were immunostained for the TLR-9 and MMP-13 markers. Subsequently, the correlation between the TLR-9 and MMP-13 staining scores and clinicopathological parameters was obtained. Higher expressions of TLR-9 and MMP-13 were found in PCa and high-grade prostatic intraepithelial neoplasia compared to benign prostatic hyperplasia tissues. Among PCa samples, a positive relationship was revealed between the MMP-13 expression and Gleason score (P < 0.001). There was a significant correlation between TLR-9 expression and regional lymph node involvement (P = 0.04). The expression patterns of TLR-9 and MMP-13 markers demonstrated a reciprocal significant correlation between the two markers in the same series of prostate samples (P < 0.001). Furthermore, the Gleason score of TLR-9high /MMP-13high and TLR-9low /MMP-13low phenotypes showed a significant difference (P = 0.002). Higher expressions of TLR-9 and MMP-13 can confer aggressive behaviour to PCa. Therefore, these markers may be used as a valuable target for tailored therapy of PCa.

In-vitro prostate cancer biomarker detection by directed conjugation of anti-PSCA antibody to super paramagnetic iron oxide nanoparticless.

Background: The main property of a successful conjugation of antibodies to nanoparticles is keeping the potency of antibody for binding the antigen, and an oriented conjugation can do that. Under such ground, this study was carried out to explore the efficiency of two conjugation methods in binding iron nanoparticles to an antibody produced against PSCA (prostate stem cell antigen) using in vitro labeling of PC3 cells. Methods: In this experimental study, we conjugated dextran-superparamagnetic iron oxide nanoparticles (dexSPIONs) to anti-PSCA antibody by two different methods, including targeting carbohydrate moieties in FC domain and the free amine group of amino acid side chains. Ultimately, Iron staining was done by anti-PSCA antibody-dexSPIONs in PC3 cells to detect antibody binding to the cells. Results: A strong blue dye was induced by iron staining in conjugated dexSPIONs on the membrane of PC3 cells by the former method than the second one. Moreover, cells treated with 20 nm diameters of dexSPIONs showed higher resolution of blue color than those treated with 100 nm nanoparticles. Conclusion: This oriented conjugation method promoted the efficiency of targeting tumor antigens, and the presence of iron particles might enhance MRI image intensity in vivo by targeting PSCA-overexpressing cells in future studies.

Lung cancer and ß-glucans: review of potential therapeutic applications.

The potential of natural substances with immunotherapeutic properties has long been studied. ß-glucans, a cell wall component of certain bacteria and fungi, potentiate the immune system against microbes and toxic substances. Moreover, ß-glucans are known to exhibit direct anticancer effects and can suppress cancer proliferation through immunomodulatory pathways. Mortality of lung cancer has been alarmingly increasingly worldwide; therefore, treatment of lung cancer is an urgent necessity. Numerous researchers are now dedicated to using ß-glucans as a therapy for lung cancer. In the present attempt, we have reviewed the studies addressing therapeutic effects of ß-glucans in primary and metastatic lung cancer published in the time period of 1991-2016.

The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells.

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays critical roles in orchestrating of immune system, especially cytokine receptors and they can modulate the polarization of T helper cells. This pathway is regulated by an array of regulator proteins, including Suppressors of Cytokine Signaling (SOCS), Protein Inhibitors of Activated STATs (PIAS) and Protein Tyrosine Phosphatases (PTPs) determining the initiation, duration and termination of the signaling cascades. Dysregulation of the JAK-STAT pathway in T helper cells may result in various immune disorders. In this review, we represent how the JAK-STAT pathway is generally regulated and then in Th cell subsets in more detail. Finally, we introduce novel targeted strategies as promising therapeutic approaches in the treatment of immune disorders. Studies are ongoing for identifying the other regulators of the JAK-STAT pathway and designing innovative therapeutic strategies. Therefore, further investigation is needed.

Direct immunomodulatory influence of IFN-ß on human astrocytoma cells.

Astrocytes actively play a pivotal role in inflammatory disease intensity of central nervous system especially multiple sclerosis (MS). Although IFN-ß is a selective therapy for MS but the role of IFN-ß in stimulating the astrocytes to produce cytokines is not clearly revealed. Therefore, it is encouraging to assess the modulatory role of IFN-ß on astrocytes of brain tissue. The aim of our study was to analyze the molecular mechanisms of recombinant IFN-ß 1a directly affecting IL-10, iNOS, MMP-9 and TIMP-1 expression in central nervous system for the first time. In this way, in vitro procedures conducted by human astrocytoma A172 and 1321N1 cell lines as a model system. The total RNA from A172 and 1321N1 cells treated with IFN-ß and LPS/IFN-γ/IFN-ß and untreated cells were extracted and evaluated for IL-10, iNOS, MMP-9 and TIMP-1 expression by real-time RT-PCR. We found a significant dose-dependent increase in IL-10 gene expression in A172 and 1321N1 cells treated with IFN-ß or LPS/IFN-γ/IFN-ß. Moreover, a significant decrease was observed in iNOS expression suggesting a similar mechanism of action for both cells. Eventually there were no significant changes concerning the modulation of the MMP-9 and TIMP-1 in response to IFN-ß treatment. In part, the immunomodulatory effect of IFN-ß may be due to increase of IL-10 and suppression of iNOS expression in astrocytes of brain tissue.

Study of NGEP expression in androgen sensitive prostate cancer cells: A potential target for immunotherapy.

BACKGROUND: Prostate cancer is one of the leading causes of cancer deaths among men. New gene expressed in prostate (NGEP), is a prostate-specific gene expressed only in normal prostate and prostate cancer tissue. Because of its selective expression in prostate cancer cell surface, NGEP is a potential immunotherapeutic target. To target the NGEP in prostate cancer, it is essential to investigate its expression in prostate cancer cells. METHODS: In the present study, we investigated NGEP expression in LNCaP and DU145 cells by real time and RT-PCR, flow cytometric and immunocytochemical analyses. RESULTS: Real time and RT-PCR analyses of NGEP expression showed that NGEP was expressed in the LNCaP cells but not in DU145 cells. The detection of NGEP protein by flow cytometric and immunocytochemistry analyses indicated that NGEP protein was weakly expressed only in LNCaP cell membrane. CONCLUSION: Our results demonstrate that LNCaP cell line is more suitable than DU145 for NGEP expression studies; however, its low-level expression is a limiting issue. NGEP expression may be increased by androgen supplementation of LNCaP cell culture medium.

Overexpression of Transmembrane Phosphatase with Tensin homology (TPTE) in prostate cancer is clinically significant, suggesting its potential as a valuable biomarker.

PURPOSE: Cancer testis antigens (CTAs) are a family of proteins typically expressed in male testicles but overexpressed in various cancer cell types. Transmembrane Phosphatase with Tensin homology (TPTE) is expressed only in the testis of healthy individuals and is a member of the family of CTAs. The current study, for the first time, examined the significance of TPTE expression in prostate cancer (PCa) tissues by generating a novel antibody marker targeting TPTE protein. METHODS: Polyclonal antibodies were prepared for TPTE-p1 and TPTE-p2 peptides, which are derived from the extracellular domains of TPTE. Anti-TPTE-p2 antibody was then used to study the extent and pattern of TPTE expression in 102 PCa and 48 benign prostatic hyperplasia (BPH) tissue samples by immunohistochemistry. The viability of cancer cell lines (PC-3 and MCF-7 cells) was also evaluated in the presence of anti-TPTE-p2 antibody using the MTT test. RESULTS: The immunohistochemical analysis demonstrated a significant increase in cytoplasmic and membrane TPTE expression in the PCa samples compared to the BPH group (both P < 0.0001). Cytoplasmic TPTE expression was positively correlated with Gleason score and PSA levels (P = 0.03 and P = 0.001, respectively). Significant correlations were identified between the levels of PSA and perineural invasion and the membrane expression (P = 0.01, P = 0.04, respectively). Moreover, anti-TPTE-p2 antibody inhibited PC-3 and MCF-7 cells proliferation compared to the control group for 24 h (P < 0.001 and P = 0.001, respectively) as well as for 48 h (P = 0.001 and P = 0.001, respectively). CONCLUSION: Our findings indicate that increased TPTE expression is associated with progression of disease. The ability of anti-TPTE-p2 antibody to recognize and target the TPTE protein makes it a potential biomarker to assess and/or target the PCa.

Impaired monocyte-derived dendritic cell phenotype in prostate cancer patients: A phenotypic comparison with healthy donors.

BACKGROUND: Dendritic cells (DCs) play a crucial role in immunity. Research on monocyte-derived DCs (Mo-DCs) cancer vaccines is in progress despite limited success in clinical trials. This study focuses on Mo-DCs generated from prostate cancer (PCA) patients, comparing them with DCs from healthy donors (HD-DCs). METHODS: Mo-DCs were isolated from PCA patient samples, and their phenotype was compared to HD-DCs. Key parameters included monocyte count, CD14 expression, and the levels of maturation markers (HLA-DR, CD80, CD86) were assessed. RESULTS: PCA samples exhibited a significantly lower monocyte count and reduced CD14 expression compared to healthy samples (p ⟨ 0.0001). Additionally, PCA-DCs expressed significantly lower levels of maturation markers, including HLA-DR, CD80, and CD86, when compared to HD-DCs (p = 0.123, p = 0.884, and p = 0.309, respectively). CONCLUSION: The limited success of DC vaccines could be attributed to impaired phenotypic characteristics. These observations suggest that suboptimal characteristics of Mo-DCs generated from cancer patient blood samples might contribute to the limited success of DC vaccines. Consequently, this study underscores the need for alternative strategies to enhance the features of Mo-DCs for more effective cancer immunotherapies.

Reduced expression of NGEP is associated with high-grade prostate cancers: a tissue microarray analysis.

New gene expressed in prostate (NGEP) is a newly diagnosed prostate-specific gene that is expressed only in normal prostate and prostate cancer cells. Discovery of tissue-specific markers may promote the development of novel targets for immunotherapy of prostate cancer. In the present study, the staining pattern and clinical significance of NGEP were evaluated in a series of prostate tissues composed of 123 prostate cancer, 19 high-grade prostatic intraepithelial neoplasia and 44 samples of benign prostate tissue included in tissue microarrays using immunohistochemistry. Our study demonstrated that NGEP localized mainly in the apical and lateral membranes and was also partially distributed in the cytoplasm of epithelial cells of normal prostate tissue. All of the examined prostate tissues expressed NGEP with a variety of intensities; the level of expression was significantly more in the benign prostate tissues compared to malignant prostate samples (P value <0.001). Among prostate adenocarcinoma samples, a significant and inverse correlation was observed between the intensity of NGEP expression and increased Gleason score (P = 0.007). Taken together, we found that NGEP protein is widely expressed in low-grade to high-grade prostate adenocarcinomas as well as benign prostate tissues, and the intensity of expression is inversely proportional to the level of malignancy. NGEP could be an attractive target for immune-based therapy of prostate cancer patients as an alternative to the conventional therapies particularly in indolent patients.