CD1a-positive Dendritic Cells Research Articles

Analysis of CD1a-Positive Monocyte-Derived Cells in the Regional Lymph Nodes of Patients with Gallbladder Cancer.

Dendritic cells (DCs) are known to be major antigen-presenting cells, and lymph nodes (LNs) play an important role in DC-mediated immune response. CD1a is known as a marker of monocyte-derived DCs. The present study focused on the infiltration of CD1a-positive DCs (CD1a-DCs) into regional LNs in 70 cases of gallbladder cancer (GBC). After univariate analyses, the results showed that LN infiltration by CD1a-DCs was associated with unfavorable clinical outcomes in patients with GBC, with all cases categorized in the CD1a-DCs high group had nodal metastasis. LN infiltration by CD1a-DCs was not an independent prognostic factor identified by multivariate analyses. After subgroup analyses of cases with LN metastasis (n = 32), no significant impacts of CD1a-DCs infiltration into metastatic LNs were observed. In contrast, CD1a-DCs infiltration into primary tumors had a significant impact on surgical outcomes. The results of strong confounding between CD1a-DCs and LN metastasis support the theory that CD1a-DCs are developed from monocytes at tumor sites. As the results of previous research focused on CD1a-DCs infiltration into regional LNs of other organs varied, the role and significance of CD1a-DCs infiltration in regional LNs may be different according to the tumor histology or its primary site. Thus, further studies are needed to clarify the role and significance of CD1a-DCs infiltration into regional LNs of solid cancers.

Chemoradiotherapy and Lymph Node Metastasis Affect Dendritic Cell Infiltration and Maturation in Regional Lymph Nodes of Laryngeal Cancer.

Dendritic cells (DCs) are the most specialized antigen-presenting cells, and lymph nodes (LNs) play an important role in the DC-mediated T-cell response. We evaluated the infiltration of CD1a-positive DCs (CD1a-DCs), i.e., immature DCs, and S100-positive dendritic cells (S100-DCs), a mixture of immature and mature DCs, in 73 cases of laryngeal cancer and its regional LNs. Among them, 31 patients underwent radiotherapy (RT) or chemoradiotherapy (CRT) prior to surgery. No significant difference was found for CD1a-DC infiltration in the primary tumors, metastatic LNs and non-metastatic LNs, while S100-DCs were significantly fewer in number in the primary tumors and metastatic LNs compared to non-metastatic LNs. The cases which showed a high infiltration of S100-DCs in the metastatic LNs appeared to show a favorable prognosis, although statistical significance was not reached. In the RT/CRT group, the infiltration of the CD1a-DCs and S100-DCs was less in the primary tumors and metastatic LNs compared to the treatment-naive group. Conversely, the RT/CRT group showed higher CD1a-DC and S100-DC numbers in the non-metastatic LNs compared to the treatment-naïve group. Thus, DC maturation in metastatic LNs plays an important role in tumor immunity in laryngeal cancer, and the infiltration of DCs into the primary tumor and metastatic LNs is impaired by RT/CRT.

Infiltration of CD1a-positive dendritic cells in advanced laryngeal cancer correlates with unfavorable outcomes post-laryngectomy

BackgroundThe prognosis of advanced laryngeal cancer is unfavorable despite advances in multidisciplinary therapy. Dendritic cells (DCs) play a central role in antitumor immunity. Tumor-infiltrating CD1a+ DCs have been reported to be associated with clinical outcomes in carcinomas of various organs, but the clinical impact of CD1a+ DCs in laryngeal cancer remains to be unequivocally established.MethodsWe retrospectively analyzed the cases of 57 patients with Stage III or IV laryngeal cancer who underwent a total laryngectomy. Immunohistochemistry detection of CD1a, S100 and CD8 was performed on representative resected specimens. CD1a+ DCs, S100+ DCs and CD8+ cytotoxic T-lymphocytes (CTLs) were evaluated, and the cases divided into high and low groups according to the cut-off of the median values for each of these 3 parameters.ResultsCompared to the CD1a-low group, the CD1a-high group had more advanced cases and showed significantly worse disease-specific survival (DSS) (P = 0.008) and overall survival (OS) (P = 0.032). The analyses of S100 DCs and CD8+ CTLs revealed no significant impact on clinical outcomes. However, multivariate analysis revealed that infiltration of CD1a+ DCs was an independent unfavorable prognostic factor for both DSS (P = 0.009) and OS (P = 0.013).ConclusionsOur results demonstrated that the infiltration of CD1a+ DCs was associated with unfavorable clinical outcomes in patients with advanced laryngeal cancer who underwent a total laryngectomy as the initial treatment.

Langerhans cell deficiency in reticular dysgenesis

AbstractReticular dysgenesis is a rare inherited immunodeficiency characterized by the lack of blood monocytes and neutrophils and low lymphocyte counts, contrasting with normal red blood cell counts and normal or decreased platelet counts. Whether dendritic cells or macrophages, both of which derive primarily from blood monocytes, are affected in this condition remains unknown. We studied 7 patients with reticular dysgenesis. Macrophages were present in normal numbers in the dermis and in the atrophic lymphoid tissues of these patients, proving that at least some subsets of macrophages can differentiate despite very low monocyte counts. By contrast, Langerhans cells, which are CD1a-positive epidermal dendritic cells, were absent in all (n = 5) patients before bone marrow transplantation. After bone marrow transplantation, Langerhans cells were present (n = 2), suggesting that the defect is not related to keratinocyte dysfunction. A split chimeric reconstitution, characterized by the presence of autologous blood monocytes able to differentiate in vitro into CD1a-positive dendritic cells, was observed in a patient who underwent successful engraftment. These results suggest that an intrinsic cell defect is unlikely and that a bone marrow-derived factor may be defective in reticular dysgenesis; it may be responsible for the Langerhans cell defect but not involved in macrophage differentiation.

Immunohistochemical analysis of the aggregation of CD1a-positive dendritic cells in resected specimens and its association with surgical outcomes for patients with gallbladder cancer

Gallbladder cancer (GBC) is an aggressive malignancy with a poor prognosis. Antigen-presenting dendritic cells (DCs) play a central role in antitumor immunity. DCs expressing CD1a (CD1a-DCs) are considered immature DCs. The aim of this study was to evaluate the clinical impact of CD1a-DC infiltration into GBC tissue. Seventy-five patients with GBC (excluding non-invasive and intramucosal cancer) were enrolled. Immunohistochemistry for CD1a, S100 and CD8 was performed using representative surgically resected specimens. The cases were divided into a high CD1a-DC group (27 cases, 36%) and low CD1a-DC group (48 cases, 64%) according to the degree of CD1a-DC infiltration/aggregation. The high CD1a-DC group contained fewer patients with distant metastasis (P = 0.039) and more patients given postoperative chemotherapy (P = 0.038). The high CD1a-DC group had significantly longer overall survival (P = 0.001) and disease-specific survival (P = 0.002) than the low CD1a-DC group. In contrast, S100-DC and CD8+ tumor-infiltrating lymphocyte statuses were without effect on OS or DSS. The results of multivariate analyses indicated that the degree of infiltration/aggregation of CD1a-DCs was an independent prognostic factor associated with a favorable prognosis after surgery.

Vascular density and inflammatory infiltrate in primary oral squamous cell carcinoma and after allogeneic hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) recipients have been reported to have an increased risk of chronic graft versus host disease (cGVHD) and hematological and solid cancers. Oral manifestations are the first signs of cGVHD observed in the majority of patients, and oropharyngeal cancer is the most frequent secondary malignancy occurred after HSCT. In this study, we have evaluated the inflammatory infiltrate cell content and correlated with the vascular density in patients affected by primary oral squamous cell carcinoma (OSCC) from previous healthy controls and OSCC after cGVHD. Results have demonstrated that patients with OSCC after GVHD show a more consistent inflammatory infiltrate as compared with the OSCC ones. In detail, the inflammatory background composed of CD3-positive T cells, tryptase-positive mast cells, CD31-positive endothelial cells, and CD68-positive macrophages may be more pronounced in the setting of GVHD + OSCC than in the control group. By contrast, CD20-positive B cells and CD1a-positive dendritic cells were more abundant in the latter population. Finally, a positive correlation was found as between vascular density and inflammatory cell infiltration in both GVHD + OSCC and OSCC groups. Overall, these results confirm the role played by immune cells in enhancing tumor progression and angiogenesis and suggest a potential therapeutic strategy involving inhibition of recruitment of immune cells to the tumor microenvironment and blockade of pro-tumoral effects and pro-angiogenic functions.

Langerhans cell histiocytosis in children - a disease with many faces. Recent advances in pathogenesis, diagnostic examinations and treatment.

Langerhans cell histiocytosis is a rare clonal disease characterized by the proliferation of CD1a-positive immature dendritic cells. The purpose of this article was to present an updated review of recent advances in the pathogenesis, clinical features, imaging and treatment of this disease. The discovery of oncogenic BRAF mutations and the presence of proinflammatory cytokines and chemokines confirmed the unusual characteristics of this disease. Currently, children with organ involvement who do not have a good response to chemotherapy and have neurodegeneration or diabetes insipidus are the most problematic patients. Further research is needed to improve the results of treatment.

Abstract 4134: Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma

Abstract Purpose: Over the past four decades, osteosarcoma (OS) survival rates have remained stagnant. There is a need to identify novel therapies to target OS. In this study we examined the expression of Programed Death Ligand 1 (PD-L1) and defined the tumor microenvironment in OS in order to assess the feasibility of utilizing immune checkpoint inhibitors as a treatment modality. Experimental Design: PD-L1 expression in OS was examined in two patient cohorts using immunohistochemistry (IHC) (n = 48, n = 59) and expression was validated using quantitative real time PCR (qRT-PCR) (n = 21) and western blotting (n = 9). IHC was used to determine presence of tumor infiltrating lymphocytes and antigen presenting cells (APCs) in the tumor. Expression of PD-L1 was correlated with the presence of immune cells and with event free survival in OS. Results: PD-L1 is expressed in up to 25% of primary OS tumors. Of the PD-L1 positive tumors the majority were also PD-1 positive (92% vs 8%, p = 0.002). In addition, the presence of immune cells in the tumor mass was significantly associated with PD-L1 expression. Although all immune cell types examined were present in OS, only infiltration by APCs, specifically CD1a positive dendritic cells (48.6% vs. 51.4%, p = 0.0010) and CD68 positive macrophages (70.3% vs. 29.7%, p = 0.0316), was associated with worse outcomes. PD-L1 expression was significantly associated with worsened survival (21.6% pos. vs. 78.4% neg., p = 0.0146). Conclusions: For the first time we have identified PD-L1 expression or presence of CD1a or CD68 positive antigen presenting cells as prognostic markers for worsened outcome in OS. Furthermore, we show that IHC is a valid detection method for PD-L1 in OS. With up to 25% of OS patients expressing PD-L1, this study provides rational for targeting the PD-L1:PD-1 axis for immunotherapy in OS. Citation Format: Pratistha Koirala, Michael Roth, Jonathan Gill, Jordan Chinai, Sajida Piperdi, David Geller, Bang Hoang, Vincent Poon, Xingxing Zang, Richard Gorlick. Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4134.

An immunohistochemical study of CD83- and CD1a-positive dendritic cells in the decidua of women with recurrent spontaneous abortion

BackgroundThere are more and more women with recurrent spontaneous abortion (RSA). The mechanism of RSA is still unclear. Immunological factors have been postulated to play a role in the etiology of RSA. Dendritic cells (DCs) are the most potent antigen-presenting cells in the immune system, and the decidual DCs may take part in the occurrence of RSA. The difference in maturity status of decidual DCs among women with RSA and women with normal pregnancies is worthy of studying for its application to prevention and therapy.MethodsThe EnVision two-step immunohistochemical staining technique was used to detect the expression of CD83 and CD1a in the decidua of women with RSA (30 cases) and normal pregnancies (30 cases). The maturity status, distribution and quantity of DCs in the two groups were observed. Observation of the staining and cell counting were done using microscope within 30 randomly selected high-power fields (HPF, 40 × 10). All data analyses were conducted with SPSS 17.0 and the statistical significance was set at P <0.05.ResultsThe decidua from the two groups contained DCs that stained with the anti-CD83 and anti-CD1a antibody. Most of the decidual CD83+DCs from two groups were located in the stroma. There were more CD83+DCs clustered with other DCs in the stroma from women with RSA than normal pregnancies. Most of the CD1a+DCs in the decidua from the two groups are located close to maternal glandular epithelium. No difference in the location of CD1a+DCs was found in the decidua between two groups. The number of decidual CD83+DCs was statistically significantly higher in RSA women than in normal early pregnant women (14.20 ± 13.34/30 HPF versus 4.77 ± 2.64/30 HPF; t = 3.800, P = 0.001). The number of CD1a+DCs in the decidua was statistically significantly lower in RSA women compared with normal early pregnant women (3.97 ± 3.75/30 HPF versus 7.60 ± 6.08/30 HPF; t = 2.786, P = 0.008).ConclusionsThese findings suggest that the increase in the number of mature DCs and the decrease in the quantity of immature DCs in the decidua may be related to RSA. The maturation of decidual DCs may play an important role in the pathogenesis of RSA.

Association of CD1a‐positive dendritic cells with papillary thyroid carcinoma in thyroid fine‐needle aspirations

In contrast to other primary thyroid neoplasms and benign thyroid tissue, it has been demonstrated histologically that dendritic cells (DCs) are associated with papillary thyroid carcinoma (PTC). However, the presence and potential diagnostic value of DCs in thyroid fine-needle aspirations (FNAs) have not been previously described. The authors quantitatively assessed for the presence of DCs that were positive for cluster of differentiation 1a (CD1a) (a 43-49 kD protein expressed on DCs and cortical thymocytes) in cytologic samples of histologically confirmed PTC (n=31) and in a control group of benign thyroid nodules (BTNs) (n=29) using immunocytochemical staining with antibodies against CD1a. A subset of the corresponding PTCs (n=11) and BTNs (n=10) from surgical resection specimens also were assessed immunohistochemically for both CD1a and Langerin (a type II transmembrane cell surface receptor produced by Langerhans cells). CD1a-positive DCs were identified in 97% PTCs (n=30 of 31 PTCs) in thyroid FNA specimens. DCs were largely present in 2 distinct patterns: either as isolated DCs in the background (n=29 of 31) and/or associated with tumor cells (n=30 of 31). Tumor-associated DCs (mean±standard deviation: 6.44±6.13 DCs per tumor cluster) exhibited multiple dendritic cytoplasmic processes extending over and between malignant cells within groups. The 3 PTC cases with the least DCs corresponded to the follicular variant at excision. In contrast, only 31% of BTNs (n=9 of 29 BTNs; P=.0048) contained CD1a-positive DCs. When DCs were present in BTN, they were isolated primarily in the background (27%; n=8 of 29), although 17% of BTNs (n=5 of 29) contained rare DCs among thyrocytes, revealing both patterns in 4 cases. Both thyrocyte-associated DCs and background DCs were more numerous in PTC FNAs than in BTN FNAs, but only the thyrocyte-associated group of DCs was statistically significant (P<.0001 and P=.1173, respectively). Similar findings were reported in histologic samples in which all PTCs examined (n=11 of 11) contained both CD1a-positive and Langerin-positive DCs; only 20% of BTNs (n=2 of 10) contained rare DCs. CD1a-positive DCs were present in FNA specimens of PTC, typically in close association with tumor cells, whereas they were rare in BTNs. The increased presence of CD1a-positive DCs in PTC may be a useful diagnostic adjuvant.

Immunohistochemical study of CD1a-positive dendritic cells and matrix metalloproteinase-9 expression as novel prognostic markers of invasive breast carcinoma

Immunohistochemical study of CD1a-positive dendritic cells and matrix metalloproteinase-9 expression as novel prognostic markers of invasive breast carcinoma

Tumor-Infiltrating Dendritic Cells May Be Used as Clinicopathologic Prognostic Factors in Endometrial Carcinoma

To investigate the distribution of dendritic cells (DCs) at different development status in endometrial carcinoma and their relationship with clinical pathology. Samples were collected from 95 patients with endometrial endometrioid adenocarcinoma treated in Peking University People's Hospital from 2002 to 2010. Normal endometrial tissue was obtained from 40 women and served as controls. Immunohistochemistry was used to detect the expression of S100-, human leukocyte antigen (HLA)-DR-, and CD1a-positive DCs within the tumor glandular epithelium, the surrounding tumor interstitial tissue, and the equivalent normal endometrial tissue. The relationship of these DCs with clinical stage, pathology grade, myometrial invasion, and lymph node metastasis was analyzed. The rate of S100-positive DCs in the endometrial endometrioid adenocarcinoma glandular epithelium samples from the 95 patients was 48.4% (46/95), and that of the HLA-DR-positive DCs was 27.4% (26/95), which were both significantly higher (P < 0.05) than that in the control group. CD1a-positive DC was rarely expressed in endometrial endometrioid adenocarcinoma glandular epithelium. The rates of the S100- and HLA-DR-positive DCs in tumor interstitial tissue were similar to that of the control group (both, P > 0.05). The proportion of invasion of the S100- and HLA-DR-positive DCs was negatively correlated with the clinical stage and lymph node metastasis but was not correlated with the pathological grade and myometrial invasion. Dendritic cell invasion was detected in endometrial endometrioid adenocarcinoma. S100- and HLA-DR-positive DCs may have functions related to the delay of tumor progression and lymph node metastasis.

Localization of S-100 and CD1a positive dendritic cells in the human thymus

Localization of S-100 and CD1a positive dendritic cells in the human thymus

Elevated Concentrations of Liver-Expressed Chemokine/CC Chemokine Ligand 16 in Bronchoalveolar Lavage Fluid from Patients with Eosinophilic Pneumonia

Background: Eosinophilic pneumonia is characterized by the prominent accumulation of eosinophils and lymphocytes in the lung parenchyma. Liver-expressed chemokine (LEC)/CC chemokine ligand 16 (CCL16) is a novel functional ligand for H4 which is expressed on eosinophils and also an affinity ligand for CCR1, CCR2, CCR5 and CCR8 which are expressed on T lymphocytes and monocytes. The purpose of this study is to clarify the role of LEC/CCL16 in eosinophilic pneumonia. Methods: The LEC/CCL16 level was measuredusing an enzyme-linked immunosorbent assay in the bronchoalveolar lavage fluid (BALF) of 33 patients with eosinophilic pneumonia, 26 patients with sarcoidosis and 10 healthy volunteers. The cell sources of LEC/CCL16 in BALF were evaluated by immunocytochemistry. Results: The LEC/CCL16 levels in BALF from patients with eosinophilic pneumonia were significantly higher than those from patients with sarcoidosis and healthy volunteers. The BALF LEC/CCL16 levels correlated with the numbers of BALF eosinophils and lymphocytes, respectively. The BALF LEC/CCL16 levels were significantly decreased after remission in eosinophilic pneumonia. In immunocytochemistry, the LEC/CCL16 expression was clearly observed in CD1a-positive dendritic cells as well as in CD68-positive macrophages harvested from patients with eosinophilic pneumonia, but not from the controls. Conclusions: These results suggest that LEC/CCL16 produced by dendritic cells as well as by alveolar macrophages contributes to the accumulation of eosinophils and lymphocytes into the inflamed lungs of patients with eosinophilic pneumonia.

Immunohistochemical analysis of small plaque parapsoriasis: Involvement of dendritic cells

Small plaque parapsoriasis (SPP) is one of the cutaneous T-cell lymphoproliferative disorders. The aim of the present study was to show the antigenic profile of a subset of dendritic cells and lymphocytes in SPP in comparison with normal cells to provide data on the role of these two cell types in the pathogenesis of SPP. Skin biopsy specimens of lesions were obtained from 8 patients with SPP. Biopsies of the healthy skin from 9 control individuals were also analyzed. Immunohistochemistry was performed on the frozen tissue sections to reveal binding of anti-HLA Class II, anti-CD1a, anti-CD4, anti-CD8, anti-CD44, anti-CD45, and anti-CD68 monoclonal antibodies. There was a statistically significant increase in the number of CD1a(+), Langerhans cells (LCs), HLA-DR-immunoreactive and, CD1a-positive dermal dendritic cells and CD68(+) macrophages in the SPP group (p=0.008, 0.008, 0.002 and <0.0009, respectively). The number of lymphocytes positive for CD4, CD8 and CD45 was significantly higher than normal in the SPP group (p=0.015, <0.0009 and <0.0009, respectively). Our study demonstrates that both peptide- and lipid-based antigens are involved in the persistent antigenic exposure in SPP. Dendritic cells play a pivotal role in SPP by presenting antigens by both LC and dermal dendritic cells via MHC Class II and CD1a molecules. The CD68(+) macrophages are thought to be involved in the immune response in this pathology as an antigen-presenting cell.

Expression of the CD1a molecule in B- and T-lymphoproliferative skin conditions

The skin immune system is characterized by the presence of two types of CD1a expressing cells: langerhans cells and dermal dendritic cells, which are professional antigen processing and presenting cells. It is well established that several dermatoses are associated with T-cell mediated immune responses. In these pathological skin conditions, T-cells are activated by professional antigen presenting cells and dendritic cells are the most potent antigen presenting cells for both T-helper cells and T-cytotoxic cells. Therefore, it is plausible that dendritic cells are crucially involved in the pathogenesis of lymphoproliferative skin conditions characterized by the presence of a T-cell infiltrate. In this study, we examined the frequency and distribution of CD1a expressing cells and CD3+ cells in both the dermal and epidermal compartment in a wide range of lymphoproliferative dermatoses with a T-lymphoid infiltrate. In the skin conditions investigated, the CD1a molecule was highly expressed in mycosis fungoides, T-cutaneous lymphoid hyperplasia, lymphomatoid papulosis and parapsoriasis, whereas few CD1a-positive cells were observed in cutaneous B-cell lymphomas. Our study demonstrates a distinct pattern of CD1a staining in the infiltrates of cutaneous lympho-proliferative disorders which may reflect different immunoregulatory events involving T-lymphocytes and CD1a-positive dermal and epidermal dendritic cells.

Galectin-3 and CD1a-Positive Dendritic Cells Are Involved in the Development of an Invasive Phenotype in Vulvar Squamous Lesions

In this study, the expression patterns of Galectin-3 (Gal-3) and the frequency of infiltrating CD1a positive dendritic cells (DCs) were determined in 82 cases of vulvar tissues, consisting of normal squamous epithelia (NE, N = 10), vulvar condylomas (VC, N = 24), high grade vulvar intraepithelial neoplasias (HG-VIN, N = 26) of common type, and invasive keratinizing squamous cell carcinomas (SCC, N = 22) by a standard immunohistochemical method using monoclonal antibodies to investigate their differential expression in vulvar squamous dysplasia and infiltrating carcinomas with an emphasis on neoplastic transformation and progression. Gal-3 expression was cytoplasmic, nuclear or membranous in NE, VCs, and HG-VINs, with negative or weak and occasionally moderate reactivities. In SCCs, exclusively cytoplasmic staining patterns with moderate or strong reactivity in 59% of cases were observed (p < 0.0001, chi-square test); Gal-3 expression was not related with stage, grade, and recurrence. The frequency of CD1a positive DCs increased from NE and VCs to highest numbers in HG-VINs, was lowest in SCCs (p < 0.0001, ANOVA), and was not related with stage and grade, but with recurrence in SCCs (p = 0,048, t-test). This study indicates that qualitative and quantitative changes of Gal-3 immunoexpression and infiltration by CD1a positive DCs in vulvar NE, VCs, and HG-VIN lesions, respectively, compared with SCCs play a role in the development of an infiltrative phenotype, and may provide adjunctive criteria in the diagnosis of invasion of vulvar squamous epithelia.

Prognostic Value of Tumor-Infiltrating Dendritic Cells in Colorectal Cancer: Role of Maturation Status and Intratumoral Localization

The clinical significance of tumor-infiltrating dendritic cells has been reported in a variety of human solid tumors as shown by the correlations found between the presence of tumor-infiltrating dendritic cells and clinical prognosis. In this study, we evaluated whether there is an association between the presence and maturation status of tumor-infiltrating dendritic cells, T lymphocytes, and clinical course in 104 primary tumor samples of patients with colorectal cancer. Dendritic cells were identified with four different markers (S-100, HLA class II, CD208, and CD1a) in double immunohistochemistry, with laminin as second marker to support the exact localization. Tumor-infiltrating dendritic cells showed a distinct infiltration pattern based on their maturation status. CD1a-positive dendritic cells resided in the advancing tumor margins in relatively high numbers, whereas mature CD208-positive dendritic cells were sparsely present in the tumor epithelium but mainly distributed in the tumor stroma and advancing tumor margin. Furthermore, high infiltration of CD1a-positive dendritic cells in the tumor epithelium was significantly correlated to the infiltration of CD4 lymphocytes (P = 0.006). Patients with relatively high numbers of mature CD208-positive infiltrating dendritic cells in the tumor epithelium had a shorter overall survival (P = 0.004). In addition, patients with relatively high numbers of CD1a-positive dendritic cells in the advancing margin of the tumor had a shorter disease-free survival (P = 0.03). We found that tumor-infiltrating dendritic cells had preferential infiltration sites within a tumor, affected local tumor cell-immune cell interactions, and correlated to the clinical prognosis of colorectal cancer patients.

Human cytomegalovirus inhibits differentiation of monocytes into dendritic cells with the consequence of depressed immunological functions.

Human cytomegalovirus (HCMV) infections in immunocompromised patients are associated with impaired immunological functions. Blood monocytes, which can differentiate into dendritic cells upon cytokine stimulation, play a central role in adequate immune reactivity and are believed to carry latent HCMV. We demonstrate here that HCMV infection of monocytes results in a block in the cytokine-induced differentiation of monocytes into functionally active CD1a-positive dendritic cells, which exhibited severely depressed immunological functions in vitro. The HCMV-infected cells exhibited a significantly reduced ability to endocytose fluorescein isothiocyanate-labeled dextran particles as well as a more than 90% reduced ability to migrate in response to the chemoattractant factors RANTES, MIP-1alpha, and MIP-3beta. Interestingly, HCMV-infected cells expressed high levels of the costimulatory molecule CD86, in contrast to the low levels of expression that was observed on uninfected monocytes and uninfected immature dendritic cells. Furthermore, HCMV-infected CD1a-negative cells were unable to induce a T-cell response. Thus, these observations suggest that HCMV infection of monocytes in vitro blocks cytokine-induced dendritic cell differentiation, and since dendritic cells play a central role in initiating immune responses, these findings suggest a powerful tactic to avoid immune recognition and to blunt the immune response at early phases of infection.

Dendritic cell and effector cell infiltration in soft tissue sarcomas with reactive lymphoid hyperplasia

The lymph node is the site of antigen presentation, and dendritic cells are sentinels for anti-tumor immunity. However, little is known about the histological features of lymph nodes and dendritic cells in soft tissue sarcomas. The reactive lymph node and infiltration of dendritic cells or effector cells were studied histologically in 10 soft tissue sarcomas with reactive lymphoid hyperplasia. The cases included four malignant fibrous histiocytomas, two malignant peripheral nerve sheath tumors, one synovial sarcoma, one epithelioid sarcoma, one malignant granular cell tumor, and one liposarcoma. The proportions of the T zone, lymphoid follicle, and lymphoid sinus (which was occupied by cells immunopositive for antibodies against CD3, CD20, or CD68) were 33.4% ± 11.0%, 6.1% ± 4.9%, and 13.5% ± 6.5%, respectively. T zone hyperplasia was observed in all cases, and sinus histiocytosis was found in four. The proportion of the T zone in regional lymph nodes of soft tissue sarcoma patients was significantly higher than that in adult autopsy cases without a cancer history. CD8-, TIA-1-, or granzyme B-positive effector cells were found in each sarcoma tissue. Whereas CD1a-positive dendritic cells were not detected, S-100 protein-positive or CD83-positive dendritic cells were observed in five sarcoma tissues. The coefficient correlation between the numbers of effector cells and dendritic cells positive for CD83 or S-100 protein were demonstrated. Although this is a preliminary report, the present study demonstrated that some soft tissue sarcoma patients showed reactive lymphoid hyperplasia. Furthermore, the association between the infiltration of dendritic cells and that of effector cells was observed in patients with soft tissue sarcomas.