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PubMed1998

Progression of pancreatic intraductal neoplasias to infiltrating adenocarcinoma of the pancreas.

Pancreata with cancer also frequently have intraductal proliferative lesions, suggesting an association between pancreatic cancer and these lesions. We present three cases in which atypical papillary hyperplasia of the pancreas was documented 17 months to 10 years before the development of an infiltrating adenocarcinoma of the pancreas. The first patient was a 70-year-old woman who underwent pancreaticoduodenectomy for adenocarcinoma of the pancreas. Atypical papillary duct hyperplasia extended to the pancreatic neck margin of resection, but the margin was negative for infiltrating carcinoma. Nine years later, an infiltrating adenocarcinoma developed in the remaining pancreas. The second patient was a 58-year-old man who underwent distal pancreatectomy for chronic pancreatitis with pseudocyst. Histologic examination showed chronic pancreatitis and multiple foci of atypical papillary duct hyperplasia. Ten years later, the patient underwent a Whipple procedure for infiltrating adenocarcinoma of the pancreas. The third patient was a 46-year-old woman with recurrent pancreatitis who underwent a Whipple procedure. Histologic examination showed atypical papillary duct hyperplasia and chronic pancreatitis but no infiltrating carcinoma. At the time of surgery, the tail of the pancreas was grossly and radiographically normal. Seventeen months later, a malignant pleural effusion developed, and postmortem examination showed infiltrating adenocarcinoma in the tail of the pancreas. In the cases presented, atypical papillary hyperplasia was documented 17 months, 9 years, and 10 years before the development of infiltrating adenocarcinoma of the pancreas, supporting the concept that there is a progression from intraductal hyperplasia to infiltrating carcinoma of the pancreas, just as there is a progression from adenoma to infiltrating carcinoma in the colorectum. Based on evidence that these intraductal lesions are precursor lesions to infiltrating adenocarcinoma of the pancreas, we suggest that the term "hyperplasia" be replaced by the more specific term "pancreatic intraepithelial neoplasia."

Adenocarcinoma↗

PubMed2002

Expression of the chemokines MCP-1/CCL2 and RANTES/CCL5 is differentially regulated by infiltrating inflammatory cells.

BACKGROUND: Chemokines are involved in the regulation of the cellular renal infiltrate in glomerulonephritis; however, it is unclear to which degree resident glomerular cells or infiltrating leukocytes contribute to the formation of chemokines in glomerular inflammatory lesions. We therefore examined whether monocytes/macrophages play a role in the expression of the C-C chemokines MCP-1/CCL2 and RANTES/CCL5 in renal tissue in a lipopolysaccharide (LPS)-induced model of inflammation, where previously we have shown increased glomerular RANTES expression and glomerular infiltration of ED-1-positive cells. METHODS: Inflammatory lesions were induced by an intraperitoneal injection of LPS. The infiltration of monocytes into the glomerulus was reduced by two experimental approaches. First, rats were depleted of monocytes by the use of specific monocyte-antisera or by cytotoxic drugs. Second, the infiltration of monocytes into the kidney was reduced by using intercellular adhesion molecule-1 (ICAM-1) knockout mice. RESULTS: Both experimental approaches demonstrated a significant reduction in the number of infiltrating monocytes/macrophages after lipopolysaccharide injection. This reduction in the infiltration of inflammatory cells was associated with significantly reduced RANTES/CCL5 mRNA expression. However, MCP-1/CCL2 mRNA expression was not inhibited after the LPS injection by monocyte/macrophage depletion. Also, the increase in nuclear factor-kappaB (NF-kappaB) binding activity after the LPS injection was not reduced in pretreated animals. The experiments therefore demonstrate that infiltrating monocytes/macrophages contribute to increased RANTES/CCL5 mRNA expression in inflammatory renal lesions, whereas MCP-1/CCL2 mRNA expression and NF-kappaB activation were not reduced by monocyte/macrophage depletion. CONCLUSION: MCP-1/CCL2 released from renal tissue upon stimulation plays a major role in the regulation of monocyte/macrophage infiltration, which contributes significantly to increased renal RANTES/CCL5 expression. This cross-talk between resident renal cells and monocytes/macrophages is therefore likely to boost the number of infiltrating inflammatory cells.

Animals↗

PubMed2005

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.

Adolescent↗

PubMed1999

Contact lens-induced peripheral ulcers with extended wear of disposable hydrogel lenses: histopathologic observations on the nature and type of corneal infiltrate.

PURPOSE: Contact lens-induced peripheral ulcer (CLPU), a sudden-onset adverse event observed with extended wear of hydrogel lenses, is characterized by a single, small, circular, focal anterior stromal infiltrate in the corneal periphery or midperiphery. The condition is always associated with a significant overlying epithelial loss and resolves in a scar. The aim was to determine, by using histopathologic techniques, the nature and type of the corneal infiltrate of these events. METHODS: Three CLPUs observed in three patients using disposable hydrogel lenses on an extended-wear schedule were examined. The eye was topically anesthetized, and a corneal section including all of the infiltrate was taken. A small triangular piece of conjunctiva immediately adjacent to the infiltrate was sectioned. The tissue was immediately fixed, processed, stained using hematoxylin and eosin and periodic acid-Schiff stains, and examined by using light microscopy. RESULTS: The diameter of these three corneal infiltrates varied from 0.3 to 0.6 mm. Histopathology of the corneal sections revealed a focal epithelial loss corresponding to the infiltrated stroma in all three patients. The adjacent epithelium was thinned. Bowman's layer was intact in two patients and had a localized area of loss in the remaining patient. The anterior stroma was densely infiltrated with polymorphonuclear leukocytes and had focal areas of necrosis. The infiltration was most dense in the region immediately underlying Bowman's layer. No other infiltrative cell type was seen in any of the sections. Histopathology of the conjunctiva revealed features consistent with normal conjunctival tissue. CONCLUSIONS: On histopathology of CLPU, distinctive features (i.e., focal corneal epithelial loss, an intact Bowman's membrane, and a localized infiltration of the anterior stroma with polymorphonuclear leukocytes) were seen. These features suggest that the event is an acute inflammatory process and probably noninfective in nature.

Adolescent↗

PubMed2001

Anesthetic efficacy of infiltrations in mandibular anterior teeth.

The purpose of this prospective, randomized, double-blind study was to measure the degree of anesthesia obtained with a labial infiltration of either 2% lidocaine with 1:50,000 or 2% lidocaine with 1:100,000 epinephrine in mandibular anterior teeth. Another objective was to measure the degree of anesthesia obtained with a lingual infiltration of 2% lidocaine with 1:100,000 epinephrine in mandibular anterior teeth. Through use of a repeated-measures design, 40 subjects randomly received a labial infiltration at the lateral incisor apex of either 1.8 mL of 2% lidocaine with 1:100,000 epinephrine or 1.8 mL of 2% lidocaine with 1:50,000 epinephrine at 2 separate appointments. An additional 40 subjects received a lingual infiltration at the lateral incisor apex of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine. The mandibular anterior teeth were blindly pulp tested at 4-minute cycles for 60 minutes postinjection. No response from the subject to the maximum output (80 reading) of the pulp tester was used as the criterion for pulpal anesthesia. Anesthesia was considered successful when 2 consecutive 80 readings were obtained. For the 3 infiltrations, success rates for the lateral incisor ranged from 43 to 50%. Adjacent teeth had success rates of 27 to 63%. There was no significant difference (P > 0.05) in success between the labial infiltration of 2% lidocaine with 1:100,000 epinephrine and 2% lidocaine with 1:50,000 epinephrine or the lingual infiltration of 2% lidocaine with 1:100,000 epinephrine when compared with the labial infiltration of 2% lidocaine with 1:100,000 epinephrine. Duration of pulpal anesthesia declined steadily for all solutions over the 60 minutes. In conclusion, the success rate of 43-50% and declining duration of pulpal anesthesia over an hour indicates that a labial infiltration of 1.8 mL of either 2% lidocaine with 1:100,000 epinephrine or 1: 50,000 epinephrine or a lingual infiltration of 2% lidocaine with 1:100,000 epinephrine over the lateral incisor apex cannot be recommended clinically to provide profound pulpal anesthesia.

Adult↗

PubMed2001

[Relationship among lymphatic metastasis, pericancerous lymphocytic reaction and dendritic cell infiltration in laryngeal carcinoma cells].

OBJECTIVE: To study the role and the clinical significance of dendritic cell infiltration against tumor cells in patients with laryngeal squamous cell carcinoma. METHODS: Immunohistochemical method using S-100 protein antibody was employed to detect dendritic cells (DC) on paraffin-embedded tissue sections from 23 patients with laryngeal squamous cell carcinomas. The relationships among the density of dendritic cell infiltration in laryngeal carcinomas and cervical lymphatic metastasis, pericancerous lymphocytic reaction and other clinicopathologic parameters were observed. RESULTS: The numbers of dendritic cells infiltrating among laryngeal carcinoma cells in patients with no cervical lymph metastasis was significantly larger than those with cervical lymphatic metastasis (t = 4.889, P < 0.01). Significant increase DC infiltration among laryngeal carcinoma cells was found in the group with intensively positive reaction of pericancerous lymphocyte than in the medium and weakly positive groups. The number of infiltrating dendritic cells in patients who had survived more than 5 years was significantly larger than those survived less than 5 years (t = 4.423, P < 0.01). The numbers of the infiltrating dendritic cells in patients with well-differentiated squamous cell carcinoma and poorly differentiated squamous cells carcinoma were 2.2 +/- 1.07 and 14.6 +/- 7.14 respectively, which were significantly different (q = 4.532, P < 0.05). CONCLUSION: The study showed that DC infiltration among laryngeal squamous carcinoma cells played an important role in the host immune reaction against tumor. It indicated that when the density of infiltrating DC is higher, the patients had less chance of cervical lymph metastasis and may have a longer survival time. There was a coordinative effect between DC infiltration in tumor cells and pericancerous lymphocyte reaction. Thus, the DC infiltration among laryngeal squamous cells could be used as an index of prognosis.

Aged↗

PubMedDate not supplied

Prognostic significances of tumor-infiltrating S-100 positive dendritic cells and lymphocytes in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: To investigate the prognostic significances of dendritic cells and lymphocytes infiltration in hepatocellular carcinoma. METHODOLOGY: The clinicopathological and follow-up data of 44 patients with hepatocellular carcinoma, who underwent curative resection of tumor in our hospital from January 1995 to July 1996, were collected. Immunohistochemical staining was employed to detect the S-100 positive dendritic cells in the tumor tissue, and lymphocytes infiltration was evaluated simultaneously. The relationship of the tumor-infiltrating dendritic cells and lymphocytes to the postoperative recurrence-free time and survival rate was analyzed. RESULTS: Either the tumor-infiltrating dendritic cells or the tumor-infiltrating lymphocytes alone had no significant relationship to the postoperative recurrence-free time and survival rate. By taking into consideration both tumor-infiltrating dendritic cells and lymphocytes simultaneously, the patients were classified into two groups. Group A included patients having dendritic cell counts > or = 20 cells/10 high power fields together with positive lymphocytes infiltration (n = 17), and group B consisted of patients having dendritic cell count > or = 20 cells/10 high power fields but with negative lymphocytes infiltration or dendritic cell count < 20 cells/10 high power fields with either positive or negative lymphocytes infiltration (n = 27). There were no significant differences in clinicopathological features between two groups. The recurrence-free time was markedly longer in group A as compared with group B, with a median time of 21.6 months for group A and 4.1 months for group B (P < 0.05). The 1-, 3-, 4-year survival rates were significantly greater in group A than those in group B, being 83.5% vs. 42.2%, 61.8% vs. 28.4% and 48.7% vs. 23.0%, respectively (P < 0.01). CONCLUSIONS: Marked infiltration of dendritic cells together with lymphocytes in tumor tissue was closely related to the improved clinical prognosis in patients with hepatocellular carcinoma, and represented as an independent prognostic factor.

Carcinoma, Hepatocellular↗

PubMedDate not supplied

Infiltration of S-100 protein positive dendritic cells and peritoneal recurrence in advanced gastric cancer.

We investigated the influence of the infiltration of S-100 protein positive dendritic cells on peritoneal recurrence of carcinoma in 113 patients who had undergone curative resection for gastric carcinoma invading beyond the muscularis propria. The infiltration of dendritic cells was classified into marked and slight. In patients with marked infiltration, peritoneal recurrences were rare, the rate being 5.6%, with a statistical difference compared to the rate of 20.3% with slight infiltration (p < 0.05). When patients were classified into infiltrative and expanding types with regard to the mode of invasion, patients with a marked infiltration survived longer than did those with slight infiltration in the infiltrative type carcinoma (p < 0.01). Such relationship was also observed when width of the serosal invasion was less than 4 cm in diameter (p < 0.01). Analysis of the pattern of recurrence revealed that infiltration of dendritic cells may prevent peritoneal recurrences in patients with advanced gastric cancer which has infiltrative mode of invasion.

Dendritic Cells↗

PubMed1991

[The excisional range of tracheal infiltration of the thyroid cancer].

We studied histopathologically the infiltrative modes in 17 cases with tracheal infiltration of the thyroid cancer, and studied its excisional range. 1) Macroscopically, morphologies in the regions of the trachea were divided into 3 types. Types I and II were noted in 4 cases for each and Type III was noted in 9 cases. 2) When the infiltrative modes in the trachea were divided into localized and infiltrative types, localized type was noted in all cases of type I, and infiltrative type was noted in all cases of Type II. The both types were noted in 2 cases and 7 cases of Type III, respectively. 3) Infiltrative region of the tracheal mucous membrane in all cases of Types I and III was localized in the range of the infiltrative region of the extratracheal mucous membrane. The infiltrative region of the tracheal mucous membrane was wider in 2 cases of Type II comparing with that of the extratracheal mucous membrane. It is considered that radical treatment of types I and III can be obtained by the excisional range of the infiltration of the extratracheal mucous membrane. Operative diagnosis is necessary because wider range infiltration of the cancer is observed in the tracheal mucous membrane of Type II.

Adenocarcinoma↗

PubMed1987

Interstitial mononuclear cell infiltration in Heymann nephritis.

Interstitial mononuclear cell infiltration in rats during the development of autoimmune Heymann nephritis (HN) was studied using the fine-needle aspiration biopsy (FNAB) technique. The results were compared with those obtained by immunohistochemical studies of infiltrating T helper (T-h) and T suppressor/cytotoxic (T-s) cells, and with traditional histopathological and immunofluorescence examinations. Three weeks after initial immunization with isolated tubular brush border antigen, when the histopathological finding was quite normal, FNAB revealed increased numbers of interstitial blast cells, large granular lymphocytes and activated lymphocytes. These increases reached significant levels 2 weeks after a booster injection and were still prominent in a few rats with manifest membranous glomerulonephritis (MGN) and proteinuria 14 weeks after initial immunization. Immunohistochemical staining 3 weeks after immunization showed a significant increase in T-h cells in peritubular regions. Infiltration decreased successively 2 weeks after the booster and during manifest MGN. On the other hand, the mean number of cortically infiltrating T-s cells successively increased during the course of the study and this increase had reached a statistically significant level 2 weeks after the booster. Prominent T-s infiltration appeared in a few rats 2 weeks after the booster and when MGN was histopathologically manifest, and it was then associated with histopathologically detectable interstitial mononuclear infiltration and also with blast cell infiltration in FNAB. Our results suggest linkage between tubulointerstitial lesions in HN and cell-mediated immunoreactivity, and that severe interstitial inflammation is associated with T-s cell infiltration. Cytological interpretation indicated that infiltrating blast cells were plasmablasts, which may imply local antibody production, especially since anti-brush border antibody titres and blast cell infiltration simultaneously reached maximum levels 2 weeks after the booster.

Animals↗

PubMedDate not supplied

Expression and prognostic significance of HLA class I, ICAM-1, and tumor-infiltrating lymphocytes in esophageal cancer.

Most solid malignancies show some degree of lymphoid infiltration suggesting a specific immunologic host vs. tumor reaction. Tumor-infiltrating lymphocytes (i.e., CD3 + T-lymphocyte subsets), the human leukocyte antigen (HLA) class I molecules, and the intercellular adhesion molecule-1 (ICAM-1) are key factors involved in T-cell-mediated immune surveillance. The present study was designed to assess the expression pattern of intratumoral lymphocyte infiltrates and their relationship to HLA class I and ICAM-1 expression with regard to primary esophageal carcinoma and to evaluate their prognostic influence. Representative samples of primary tumors were obtained from 55 patients who had undergone radical en bloc esophagectomy. Frozen sections of these tumors were stained with monoclonal antibodies directed against CD3 for the assessment of tumor-infiltrating lymphocytes, HLA class I, and ICAM-1. The mean postoperative observation period was 19.5 months (range 5 to 45 months). Lymphocyte infiltration was absent in four tumors (8%), whereas 31 tumors (64%) showed moderate and 13 (27%) showed strong infiltration. HLA class I expression was deficient in 24 tumors (45%). Coexpression of HLA class I and ICAM-1 was significantly associated with lymphocyte infiltration of the tumor. Kaplan-Meier analyses revealed a significant beneficial influence on relapse-free survival for patients with lymphocyte infiltration of primary tumors compared to those with no lymphocyte infiltration of tumors (median 4 months vs. 18 months; P <0.002) and for HLA class I+ tumors compared to HLA class I- tumors (median survival >18 months vs. 7 months; P = 0.0081). The present data support the hypothesis that T-cell-mediated immunity may influence the fate of patients with esophageal cancer.

CD3 Complex↗

PubMed2000

Infiltrating dendritic/Langerhans cells in primary breast cancer.

It is fully anticipated that dendritic cells (DCs) will become a mainstay for inclusion in biological therapies for patients with cancer including breast cancer. To elucidate the cellular composition of DCs infiltrating human breast cancers, we investigated the correlations between the density of infiltrating DCs and some clinicopathological factors of breast cancer patients, examined cytokine expression on cancer cells and finally, assessed the numbers of CD45RO+ tumor infiltrating lymphocytes (TIL). Tissues adjacent to cancer nests contained significantly more S-100 protein+ and S-100 protein+ CD1a- DCs, but less CD1a+ DCs, than the nests. In invasive ductal carcinomas infiltration by S-100 protein+ DCs within and adjacent to nests, CD1a+ DCs within nests and S-100 protein+ CD1a- DCs adjacent to nests was denser than that in non-invasive carcinomas. With respect to the histological subtypes, there were fewer DCs in scirrhous carcinomas. Patients with stage IV disease had significantly fewer DCs of primary lesions than at other clinical stages. There were good correlations between infiltration by S-100 protein+ DCs and expression of the cytokines GM-CSF, IL-1alpha and TNF-alpha on cancer cells and between GM-CSF expression and S-100 protein+ CD1a- DCs. There was a close correlation between CD45RO+ TIL and S-100 protein+ DC densities both within and adjacent to the cancer nests and the S-100 protein+ CD1a- DC density adjacent to the cancer nests. Despite extensive immunoelectron microscopic observation, CD1a+ DCs within cancer nests contained only few Birbeck's granule-like structure. These data indicate that cancer nests are infiltrated predominantly by CD1a+ DCs, whereas S-100 protein+ CD1a- DCs predominate in surrounding tissues, and a infiltration by DCs may require cytokine expression on cancer cells and simultaneous lymphocyte infiltration. The findings of this clinicopathological study indicate the importance of evaluating simultaneously the types and localizations of infiltrating DCs in cancer tissues.

Adenocarcinoma, Scirrhous↗

PubMed2003

Clinical significance of immune cell infiltration within gallbladder cancer.

To investigate the pathophysiological significance of infiltrating antitumour immune cells, we evaluated the quantity of immune cell intratumoral infiltration in 110 surgically resected gallbladder specimens by immunohistochemistry. We examined 45 cases of gallbladder cancer and 65 cases of benign gallbladder diseases for CD4(+) T cells, CD8(+) T cells, natural killer cells (NKCs), and dendritic cells (DCs). High levels of CD4(+) T cell, CD8(+) T cell, NKC, and DC infiltration were recognised in 51.1% (23 out of 45), 37.8% (17 out of 45), 33.3% (15 out of 45), and 48.9% (22 out of 45) of cancer specimens, respectively. High numbers of infiltrating CD4(+) and CD8(+) T cells correlated with decreasing tumour invasion, and high numbers of infiltrating DCs correlated with decreasing lymph-node tumour metastasis. Furthermore, increased infiltration of CD4(+) and CD8(+) T cells and DCs exhibited a significant correlation with prolonged survival. NKC infiltration, however, did not correlate with any of the clinicopathological factors examined. Additionally, high levels of infiltration were not identified in specimens from benign diseases, consistent with the cancer-specific activity of CD4(+) and CD8(+) T cells and DCs. In this study, we demonstrate that CD4(+) and CD8(+) tumour-infiltrating lymphocyte and DCs, but not NKCs, are important factors in the accurate prognosis of survival after surgical removal of gallbladder adenocarcinoma.

Adenocarcinoma↗

PubMed1993

Lesion-specific activation of cloned human tumor-infiltrating lymphocytes by autologous tumor cells: induction of proliferation and cytokine production.

To investigate the mechanisms by which tumor-infiltrating lymphocytes exert their antitumor effects, tumor-specific tumor-infiltrating lymphocyte clones, as well as autologous tumor cell lines from primary and secondary tumors of two patients during the course of melanoma progression were established. Enrichment for tumor-infiltrating lymphocytes expressing CD25, as well as low concentrations of interleukin-2 (30 IU/ml) in the culture medium, led to a preferential outgrowth of cells that express the high-affinity interleukin-2 receptor. All of these expressed CD2, CD3, CD11, and CD25. Coculture of tumor-infiltrating lymphocyte clones with irradiated, autologous tumor cells induced an up to 480% greater proliferative responses than recombinant interleukin-2 alone. Approximately 60% of the tumor-infiltrating lymphocyte clones showed cytotoxicity against the relevant tumor in a 4-h 51Cr-release assay. When tested in an 18-h 51Cr-release assay, the number of tumor-infiltrating lymphocyte clones exhibiting cytotoxicity against the relevant tumor increased to over 85%. In response to autologous tumor cells, nine of 15 clones secreted interferon-gamma, tumor necrosis factor-alpha, or both. Cytokine production was not restricted to either CD4+ or CD8+ T cells because both CD4+ and CD8+ tumor-infiltrating lymphocyte clones secreted cytokines. Tumor-infiltrating lymphocyte tumor interaction appears to be lesion specific because induction of proliferation and cytokine production, as well as susceptibility to cytolysis, was found not only restricted to the autologous system, but also to the specific lesion. The pattern of tumor-infiltrating lymphocyte tumor interaction specificity indicates a possible loss of antigens expressed on the tumor during disease progression.

Cell Division↗

PubMed2003

Density of neoplastic lymphoid infiltrate, CD8+ T cells, and CD1a+ dendritic cells in mycosis fungoides.

BACKGROUND/AIMS: CD8+ T cells and epidermal/dermal dendritic cells expressing CD1a are found among neoplastic CD4+ T cells in mycosis fungoides (MF) lesions. This study analysed the relation of CD8+ tumour infiltrating lymphocytes (TILs), CD1a+ epidermal Langerhan's cells (LCs), and dermal dendritic cells (DDCs) to clinicopathological parameters in 46 MF cases. METHODS: Pretreatment diagnostic biopsy specimens of 46 MF cases were submitted to histological analysis and immunohistochemistry. Four histological grades were defined based on the density of the neoplastic infiltrate: grade 1 (mild superficial perivascular infiltrate), grade 2 (moderate superficial perivascular infiltrate with some tendency to confluence), grade 3 (pronounced superficial band-like infiltrate), and grade 4 (deep nodular infiltrate). Epidermotropism was scored as low, moderate, or high. Numbers of CD8+ T cells and of dermal and epidermal CD1a+ cells were scored as 1 (low), 2 (moderate), and 3 (high). Correlations between these parameters and clinical data (age, sex, clinical type of lesions, stage, response to treatment, and recurrence) were analysed by the chi(2) test. RESULTS: Numbers of TILs and DDCs were associated with subepidermal infiltrates, being lower in less dense infiltrates, whereas there was no association between epidermal CD1a+ cells and the analysed parameters. Complete remission in treated patients was related to subepidermal infiltrates but not to TILs, LCs, or DDCs. CONCLUSIONS: These results support the notion that CD8+ cells and dermal CD1a+ cells are active against tumour cells. MF with low numbers of TILs could represent an early stage of the disease, before TILs are activated against tumour specific antigens.

Adult↗

PubMed2006

Infiltrating neutrophils induce allospecific CTL in response to immunization with apoptotic cells via MCP-1 production.

Our previous studies demonstrated that i.p. injection of late apoptotic P388 cells caused phagocytosis by macrophages and transient infiltration of neutrophils into the peritoneal cavity. As neutrophils are known to function as effectors as well as regulators in the immune response, we examined the roles of infiltrating neutrophils in alloantigen-specific CTL induction after immunization with late apoptotic P388 cells. The CTL induction and infiltration of CD8(+) T cells into the peritoneal cavity were inhibited by depletion of neutrophils by anti-Gr-1 mAb or inhibition of neutrophil infiltration by anti-MIP-2 antibody, suggesting that neutrophils are involved in CD8(+) T cell infiltration into the peritoneal cavity. It is known that MIP-1alpha, MIP-1beta, and MCP-1 are capable of attracting CD8(+) T cells and that they are produced by neutrophils. These chemokines were detected in the peritoneal cavity, and among them, MCP-1 production was reduced remarkably by suppression of neutrophil infiltration. Moreover, infiltration of CD8(+) T cells into the peritoneal cavity as well as CTL activity was clearly reduced by administering anti-MCP-1 antibody i.p. Furthermore, the CTL induction and infiltration of CD8(+) T cells in neutrophil-depleted mice were restored significantly by administering recombinant murine MCP-1 into the peritoneal cavity. These results indicate that MCP-1 appears to link infiltration of neutrophils with CTL induction.

Animals↗

PubMed1977

The prognostic significance of lymphocytic infiltration in malignant melanoma of the choroid.

Lymphocytic and plasmocytic infiltration surrounding a malignant tumor probably represents an immunologic response of the host directed against the neoplasm. It has been documented that lymphocytic infiltration has a favorable effect on prognosis in a number of human tumor systems, including cutaneous melanoma. In the present study, 309 consecutive cases of choroidal melanoma were examined for cellular infiltration, and these data were correlated with other histologic parameters and with prognosis. A intense cellular infiltration was found in 15 tumors (4.9%) and a moderate infiltration in 37 (12.0%). Tumors with cellular infiltration were significantly larger and more vascularized than the remaining tumors, which may be related to the accessibility of the immune system to the tumor. There was a higher percentage of poorly differentiated tumors among the tumors with cellular infiltration. However, it does not appear the cellular infiltration favorably influences the prognosis of choroidal melanoma. The 5-year survival rates of patients with like cell types did not depend upon the degree of cellular infiltration demonstrated by the primary tumor. Although choroidal melanomas are capable of inciting an immune response, this response is apparently ineffective in preventing metastatic spread.

Choroid Neoplasms↗

PubMed1995

Infiltration of dendritic cells into regional lymph nodes in gastric cancer.

BACKGROUND: Dendritic cells (DC), including epidermal Langerhans cells, are potent antigen-presenting cells that can carry and present tumor antigens to helper T-cells. An immunohistochemical study was performed to clarify the relationship between the extent of infiltration by DCs in primary gastric cancer and that in the regional lymph nodes. METHODS: Paraffin blocks were prepared for staining with antibody against S-100 protein in 121 cases of gastric cancer. Infiltration of S-100 protein-positive DCs was evaluated in the primary tumor and in the peritumoral, primary, secondary, and tertiary nodes. RESULTS: The extent of infiltration by DCs into the regional lymph nodes decreased significantly with an increasing distance of the nodes from the primary tumor. Correlation of the extent of such infiltration was observed among the peritumoral, primary, secondary, and tertiary nodes. However, the extent of infiltration into the primary tumor did not correlate with that into the primary, secondary, and tertiary nodes. Infiltration by DCs of the peritumoral nodes correlated with that of the tumor, particularly when lymph node metastasis was absent. There was no significant difference in the extent of infiltration into the peritumoral nodes even when lymph nodes were involved. However, infiltration of DCs increased in the primary and secondary nodes when the primary nodes were involved. CONCLUSION: Infiltration of DCs may be regulated in the primary lesion of gastric cancer. The peritumoral lymph nodes serve as transmitters of DCs from the primary tumor to the regional lymph nodes. DCs in the regional lymph nodes are important for establishing immunologic defense mechanisms in cases of gastric cancer when metastasis is absent or limited to the primary nodes.

Dendritic Cells↗