SEARCH · PubMed Health

Results for “Infiltrative”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 379 records · Page 21Linked to original sources

PubMed1985

Immunohistologic analysis of the T-cell and macrophage infiltrate in 1,2-dimethylhydrazine-induced colon tumors in the rat.

The infiltrating mononuclear cell (MNC) type, and the localization of major histocompatability class I and class II antigens within 1,2-dimethylhydrazine (CAS: 540-73-8)-induced colonic tumors and normal colonic mucosa in WF/Hsd BR rats were investigated by immunoperoxidase staining of frozen sections with the use of monoclonal antibodies. Infiltrating T-cells stained with monoclonal antibodies W3/13, W3/25, and MRC OX 8; W3/13+ cells were predominant. The most numerous and consistently observed infiltrating cell type was an la antigen-bearing (MRC OX 6+, MRC OX 17+) macrophage. A smaller subpopulation of macrophages, staining with W3/25, showed a similar distribution within tumors. In adenomas and in some well-differentiated adenocarcinomas, the infiltrating MNC were concentrated at the tumor periphery and were in close proximity to neoplastic epithelia, but without evidence of consequent tumor cell necrosis. In all other tumors, infiltrating host cells were confined to the connective tissue stroma dividing clusters of neoplastic glands. The extent of cellular infiltration and the phenotypes of infiltrating cells did not correlate with the degree of tumor differentiation or with tumor size. Expression of MHC class I antigens (MRC OX 18) by tumor cells did not differ from that of normal epithelia, and neoplastic epithelia were uniformly negative for class II antigens (MRC OX 6, MRC OX 17). The data do not support a role for cytotoxic macrophages or T-cells in the local response to colon tumors.

1,2-Dimethylhydrazine↗

PubMed1985

Combined prostaglandin therapy and ductal formalin infiltration in neonatal pulmonary oligemia.

Prostaglandins and ductal formalin infiltration, singly and together, have been used in efforts to improve pulmonary flow in very ill newborn infants with right ventricular outflow tract obstruction. To evaluate the efficacy of concurrent use of prostaglandins and ductal formalin infiltration, we have reviewed our experience with 25 infants with right ventricular outflow tract obstruction and prostaglandin-ductal formalin infiltration therapy. Prostaglandin therapy was begun 22 +/- 21 hours (range 20 to 93 hours) before and was continued 20 +/- 18 hours (range 0 to 62 hours) following ductal formalin infiltration; prostaglandin administration was initiated at a dose of 0.05 to 0.1 microgram/kg/min and tapered postoperatively. Clinical cyanosis was diminished in 20 of 25 infants (80%) postoperatively. Systemic arterial pH and oxygen saturation both improved following prostaglandin-ductal formalin infiltration therapy from 7.35 to 7.41 (p less than 0.001) and from 35.7 to 50.3 (p less than 0.001), respectively. Persistent ductal patency (mean 219 +/- 191 days) was observed in 17 survivors of the early postoperative period (more than 14 days). Two of five infants who died within 14 days of operation had a widely patent ductus with resultant progressive congestive heart failure. The other three infants died as a result of operative technical problems, dysrhythmias, and thrombotic ductal closure, respectively. No correlation was observed between duration of ductus patency and operatively determined size of ductus, total prostaglandin dose, or duration of prostaglandin infusion. Secondary operative intervention was delayed by 92 +/- 74 days with prostaglandin-ductal formalin infiltration therapy; thus prostaglandin-ductal formalin infiltration therapy may have a role in selected neonates with right ventricular outflow tract obstruction.

Alprostadil↗

PubMed1977

[Lymphocytic and non-lymphocytic dysplasia, carcinoma in situ and infiltrating squamous cell carcinoma of the cervix (author's transl)].

The degree of lymphocytic infiltration in 490 cases of infiltrating squamous cell carcinoma, carcinoma in situ, and dysplasias of the cervix was studied. 204 cases did not show any lymphocytic infiltration at the site of dysplasias, carcinoma in situ, and infiltrating squamous cell carcinoma. The degree of lymphocytic infiltration was furthermore not related to the grade of dysplasia. Taking into account all cases it was found that 75% of carcinoma in situ and infiltrating squamous cell carcinoma remained without or with only sparse lymphocytic infiltrations.

Carcinoma, Squamous Cell↗

PubMed1995

Fatty infiltration of disrupted rotator cuff muscles.

The extent of fatty infiltration of rotator cuff muscles was evaluated on computed tomography displays using a five-point scoring system in 63 shoulders before surgery for a rotator cuff tear and in 57 of these shoulders after surgical repair of the tear (the quality of cuff repair was evaluated in these 57 shoulders by arthrography, usually coupled with computed tomography, after a mean time interval of 8 months since the procedure). Preoperatively, significant fatty infiltration of the supraspinatus muscle was uncommon. Severe fatty infiltration of the infraspinatus and subscapularis muscles was seen in some patients. In most instances, fat accumulated in those muscles whose tendons were torn; however, tendon cleavage was associated with mild fatty infiltration of the corresponding muscle in some instances, and wide tears of the supraspinatus and subscapularis muscles were sometimes accompanied with severe fatty infiltration of the infraspinatus muscle. In half the cases, fatty degenerescence of the infraspinatus muscle occurred within six months of the tendon rupture. After surgery, in most shoulders without evidence of rotator cuff leakage on the postoperative arthrogram, no further accumulation of fat occurred. However, a decrease in the amount of existing fat was rarely documented and occurred only in the supraspinatus muscle. Before and after surgery, increasing severity of the fatty infiltration of the infraspinatus muscle was associated with increasing functional impairment of the same muscle. Recurrent rotator cuff tears, which involved only the supraspinatus muscle, were considerably more common when there was severe preoperative fatty infiltration of the infraspinatus muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1994

Pancreatic duct inflammatory infiltration in the nonobese diabetic (NOD) mouse.

The pancreatic duct system during the early stages of type 1 diabetes was examined in 8-wk-old female nonobese diabetic (NOD) mice. Infiltration was seen to involve the smaller ducts while the larger ducts were usually free from ductulitis. The infiltration affected ducts both close to and remote from the islets of Langerhans. In the former situation, infiltration of the islet and that of the duct were not separable. A strong positivity for both Ia and ICAM-1 molecules was observed in all infiltrated ducts, indicating that this infiltrating process is due to the same elements as are involved in the islet inflammation and that also mononuclear cells infiltrating the nonislet ducts express adhesive mechanisms. At the ultrastructural level, endocrine cells that were mainly of the 'closed' type were observed intermingled with the ductular epithelial cells and infiltrating mononuclear cells were detected either in the connective layer or among the epithelial cells of the affected ducts.

Animals↗

PubMedDate not supplied

Nature and significance of epicardial lymphoid infiltrates in cardiac allografts.

BACKGROUND: Myocardial lymphocytic infiltration after transplantation is usually a manifestation of acute cellular rejection. However, purely endocardial infiltrates are generally not regarded as rejection (so-called "Quilty lesions"). The nature of epicardial lymphoid infiltration in cardiac allografts and its significance when observed in endomyocardial biopsies or autopsies are uncertain. METHODS: Twenty-seven cases of transplant-associated epicardial lymphoid infiltration were identified; 16 cases were identified from 1602 consecutive transplant biopsy specimens from 125 patients, and 11 from 14 autopsies, ranging from 1 to 35 months (mean 7.8 months) after transplantation. RESULTS: The infiltrates were composed of aggregates of lymphocytes and histiocytes distributed throughout the epicardium. Plasma cells were found in 52% of cases, with occasional eosinophils and rare neutrophils. Most were vascular, and four autopsy cases had follicle formation. Twenty-four cases (93%) showed a mixed population of cells in a random distribution consisting of T cells in association with fewer B cells and histiocytes. Fifteen cases (nine autopsies, six biopsies) had acute rejection, and nine autopsies had chronic vascular rejection. Fourteen of twenty-four cases (58%) showed concurrent Quilty lesion (nine autopsies, five biopsies), and the remainder showed at least one Quilty lesion in an earlier biopsy. CONCLUSION: Epicardial lymphoid infiltrates occur with significant frequency after heart transplantation and can be associated with, and mimic, acute cellular rejection. However, they exhibit morphologic and immunophenotypic features which are distinguishable from rejection-associated infiltrates.

B-Lymphocytes↗

PubMed1995

Infiltrative keratitis with contact lens wear--a review.

BACKGROUND: "Infiltrates" of white blood cells aggregating in the superficial cornea are common with corneal inflammation. The etiologies of such inflammation vary widely and include an association with contact lens wear. METHODS: This paper reviews the literature regarding corneal infiltrative keratitis with contact lens wear. Basic mechanisms in the development of corneal infiltrates as well as etiologies are presented. Associations and causes, clinical presentation, differential diagnosis, course, and treatment for corneal infiltrates in contact lens wearers are reviewed. CONCLUSIONS: Corneal infiltrates associated with contact lens wear may stem from a variety of causes including factors related to the lens material, design, condition; the lens wearing schedule; environmental factors such as external environment; and lens care patterns, procedures, and products. Individuals who wear contact lenses are also subject to the many non-contact lens-related stimuli to corneal infiltration. Accurate diagnosis and appropriate management of corneal infiltrates with contact lens wear is important, especially due to the possibility of infectious etiology.

Contact Lenses↗

PubMed1994

Morphometric analysis of infiltrating cells that adhere to the sinusoidal wall and migrate into the space of disse in the orthotopically transplanted rat liver.

To reveal the kinetics of infiltrating cells in the hepatic parenchyma after the liver transplantation, we identified the cell type (macrophages, monocytes, agranular lymphocytes, large granular lymphocytes, and neutrophils) and localization on toluidine blue-stained sections of perfusion-fixed liver grafts in rejecting and tolerant combinations and performed quantitative analysis of the density of each cell species infiltrating inside and outside the sinusoid at days 4 and 7. The number of total infiltrating cells per unit square became 9 times as high as that of an untreated liver at day 4 and 30 times as high at day 7. Macrophages accounted for a large part of the infiltrating cells both in and around the sinusoid: 72% of intrasinusoidal infiltrating cells and 88% of extrasinusoidal ones at day 4; 73% of intrasinusoidal ones and 93% of extrasinusoidal ones at day 7. The ratio of extrasinusoidal cell to intrasinusoidal cell of macrophages was 9:91 at day 4 and 34:66 at day 7, much higher than ratios of other infiltrating cells. This fact means that macrophages show a marked tendency to migrate out of the sinusoid in the liver graft. The proportion of macrophages to total infiltrating cells dropped at day 4 and went up again at day 7, while that of monocytes showed a reverse pattern. Histologically, immature macrophages, possibly derived from recipient monocytes, coexisted with vacuolated donor macrophages in the sinusoid at day 4, but the latter cells were diminished at day 7. These data indicate that transformation of recipient monocytes into macrophages in the sinusoid and subsequent extrasinusoidal migration of newly formed macrophages occur soon after the cell influx into the liver graft begins at day 4. The present study has revealed that macrophages, especially those migrating into the space of Disse, will be closely related to the pathogenesis of the liver transplantation.

Animals↗

PubMed1996

[Correlation of lymphocytic infiltration of tumor tissue with the hormonal and metabolic state in patients with breast cancer].

Lymphocyte infiltration of tumor was studied vis-a-vis hormone metabolic status, tumor tissue hormone sensitivity and tobacco smoking, in 113 breast cancer patients, aged 25-77. On the average, no correlation was established between degree of lymphocyte infiltration in breast tumor and age and menopause onset. In smoking menopausal patients, lymphocyte infiltration was found to be higher than in non-smokers (p < 0.05). There was a direct correlation between the rate of lymphocyte infiltration and the level of progesterone receptors in tumor. Some subgroups displayed a direct correlation between infiltration and sex-binding globulin, cholesterol, luteinizing hormone in blood, and lean body mass. It was matched by an inverse correlation between lymphocyte infiltration and blood-thyroid hormone concentration, urine catecholamines and free cortisol excretion and fat/lean body mass ratio. Considering the abovesaid as well as the lymphocyte ability to perform the dual function of immunocytes and hormonocytes, it is suggested that the results may be used in both the study of lymphocyte infiltration and research in means of its control.

Adult↗

PubMed1998

Contribution of E-selectin to cellular infiltration during endotoxin-induced uveitis.

PURPOSE: The selectin family is a group of early-reactive adhesion molecules that plays a role in the rolling phase of leukocytes in cellular infiltration. It has been reported that P-selectin is expressed on vascular endothelium in the iris-ciliary body 15 minutes after lipopolysaccharide (LPS) treatment in endotoxin-induced uveitis (EIU) and may contribute to the initial phase of ocular inflammation. The objective of the present study was to identify the expression pattern of E-selectin, another member of the selectin family, and to investigate the role of E-selectin during the course of EIU. METHODS: Endotoxin-induced uveitis was induced in male Lewis rats by a footpad injection of 200 microg LPS. The time-dependent expressions of E-selectin in EIU in the iris- ciliary body and the retina were studied by immunohistochemistry using wholemounts and paraffin-embedded sections and by monitoring the level of E-selectin mRNA expression. A monoclonal antibody to E-selectin and a control antibody were each injected intravenously to evaluate the effects of E-selectin inhibition on ocular inflammation at the time of maximum uveitis. In the anterior uvea, the effect was evaluated by the number of infiltrated cells and by the protein concentration in the aqueous humor 24 hours after LPS treatment; in the retina, the myeloperoxidase (MPO) activity was measured 48 hours after LPS treatment. The effect of the combined injection of anti-P-selectin and anti-E-selectin antibodies was also studied. It was then determined whether the delayed inhibition of E-selectin (6, 12, or 24 hours after LPS injection) could contribute to the early resolution of the uveitis. RESULTS: E-selectin immunoreactivity was observed on the vessel walls of the iris and retina 7 hours after LPS treatment in wholemounts and paraffin-embedded sections and remained positive for 24 hours after LPS treatment. The expression of E-selectin messenger RNA gene peaked at 6 hours and again at 18 hours after LPS treatment in the iris- ciliary body and retina. The expression returned to the basal level 24 hours after LPS treatment in the iris- ciliary body and 48 hours after LPS treatment in the retina. The selective inhibition of E-selectin significantly blocked the cellular infiltration into the aqueous humor (P < 0.005) but had a milder effect on the protein concentration in the aqueous humor (P=0.0536). The inhibition of E-selectin and P-selectin almost abrogated cellular infiltration (P < 0.001). Myeloperoxidase activity in the retina 48 hours after LPS treatment was again significantly decreased by the inhibition of E-selectin alone and by the inhibition of E-selectin and P-selectin (P < 0.0001). A single injection of anti-E-selectin antibody 6, 12, or 24 hours after LPS injection effectively blocked cellular infiltration in the aqueous humor 24 and 48 hours after LPS treatment. CONCLUSIONS: In EIU, E-selectin may be expressed on the vascular endothelium and remain after the period of expression of P-selectin and until approximately the time of maximum uveitis. The present results suggest that, in contrast to the role of P-selectin as an initiator of cellular infiltration, E-selectin may contribute to continuing cellular infiltration into the inflammatory site during inflammation, and its inhibition may contribute to the early resolution of the uveitis.

Animals↗

PubMed1998

Leukocyte infiltration and intercellular adhesion molecule-1-mediated cell interactions in immunoglobulin A nephropathy.

BACKGROUND: Mononuclear leukocytes have a role in immunoglobulin (Ig) A nephropathy. Renal leukocyte recruitment is mediated by adhesive interactions between leukocytes and their ligands on renal cells. METHODS: We assessed interstitial and glomerular leukocytes using an avidin-biotin-peroxidase method with monoclonal antibodies (MAbs) against leukocytes (CD45), beta2-integrin (CD18), macrophages (CD14), T cells (CD3) and T-cell subsets (CD4, CD8), intercellular adhesion molecule-1 (ICAM-1) (CD54), and HLA class II antigens. We analyzed their relation with the abnormal expression of ICAM-1 on proximal tubular epithelium in sequential renal sections from 57 patients with IgA nephropathy stratified by degrees of interstitial cellular infiltration as seen by light microscopy. RESULTS: In IgA nephropathy without infiltration (n = 15) and with interstitial cellular infiltration of 1+ by light microscopy (n = 11), ICAM-1 expression on vascular endothelium was unchanged with respect to that observed in the normal kidney; the proximal tubular epithelium was negative for this stain. Moreover, in IgA nephropathy with interstitial cellular infiltration greater than or equal to 2+ by light microscopy (n = 31), ICAM-1+ stain was seen on proximal tubular epithelium. The value of ICAM-1+ tubule staining was significantly (P = .0004) higher in the biopsies with a higher degree of interstitial cellular infiltration seen by light microscopy. The tubular ICAM-1+ stain was significantly associated with the number of interstitial leukocytes identified by the MAbs tested and correlated (P < .05) with CD45+ (r = 0.59), CD14+ (r = 0.54), and CD3+ (r = 0.51) interstitial leukocytes in IgA nephropathy with interstitial cellular infiltration by light microscopy. Interstitial ICAM-1+ cells and interstitial CD18+ leukocytes were correlated (r = 0.85, P < .001). Correlation was found between the value of ICAM-1+ tubule staining and the number of CD45+ (r = 0.87, P < .01), CD14+ (0.58, P < .05), and CD8+ (r = 0.68, P < .05) glomerular leukocytes. CONCLUSIONS: Our results suggest that tubular and interstitial ICAM-1+ cells may participate in adhesive interactions with interstitial leukocytes. Epithelial tubular cells expressing ICAM-1 may be a marker of tubulointerstitial disturbance upregulated by interstitial and glomerular infiltration of macrophages and T cells in IgA nephropathy.

Cell Communication↗

PubMed2002

[Infiltration of dendritic cells and lymphocytes in hepatocellular carcinoma tissue].

OBJECTIVE: To explore the clinical significances of dendritic cells and lymphocytes infiltration in hepatocellular carcinoma (HCC) tissue. METHODS: Clinicopathological data were collected from 44 patients with HCC who had under/gone curative tumor resection in our hospital. Immunohistochemical staining was used to detect the infiltration of dendritic cells in the tumor tissue, and lymphocytes infiltration was assessed simultaneously. The correlation between the infiltration of dendritic cells and lymphocytes and postoperative tumor recurrence and survival rate was analyzed. RESULTS: Tumor recurrence was markedly late in patients with dendritic cells count >/= 20 and positive lymphocytes infiltration (group A, n = 17) as compared with those who did not meet both criteria simultaneously (group B, n = 27), with a median interval of 21.6 months for group A and 4.1 months for group B (U value = 105.5, P = 0.009). The 1-, 3-, 4-year survival rates were significantly greater in group A than in group B; they were 83.5% vs. 42.2%, 61.8% vs. 28.4% and 48.7% vs. 23.0%, respectively (Log rank = 7.68, P < 0.01). CONCLUSION: The infiltration of dendritic cells and lymphocytes in HCC tissue, as an independent prognostic factor, was closely related to postoperative prognosis.

Adult↗

PubMed1999

Strong expression of the lymphoattractant C-X-C chemokine Mig is associated with heavy infiltration of T cells in human malignant melanoma.

Human malignant melanoma (MM) is a highly aggressive tumour which is particularly prone to specific local immune responses. To determine the microanatomical location and the species of chemokines possibly involved in the intricate control of cell migration and positioning of immune effector cells in primary and metastatic MM lesions, the expression of those chemokines with lymphocyte and/or macrophage chemoattractant properties was analysed by in situ hybridization. GROalpha (growth-related oncogene) and IL-8 (interleukin 8) were expressed at low levels by single melanoma cells, adjacent keratinocytes, and infiltrating leukocytes. In contrast, the lymphocyte-specific chemokine Mig (monokine induced by interferon-gamma) was strongly expressed by mononuclear cells (mainly macrophages) infiltrating the tumour margin in primary MM lesions, whereas expression was less intense in MM metastasis. IP-10 (interferon-gamma inducible protein 10) was expressed in the same loci at lower intensity. Marked infiltration of T cells was exclusively detected in those areas which exhibited strong Mig expression, whereas areas in the vicinity of tumour cells devoid of Mig expression were not infiltrated. In contrast to Mig, expression of MCP-1 (macrophage chemotactic protein-1) was weaker and mainly detected in lesional basal keratinocytes, occasionally at sites of macrophage infiltration, as well as in single melanoma cells. MIP-1alpha (macrophage inflammatory protein 1alpha) showed similar, albeit weaker expression compared with MCP-1. Other chemokines relevant for the recruitment of monocytes and lymphocytes, such as RANTES (regulated on activation, normal T cells expressed and secreted) and MIP-1beta, were barely detectable. In summary, the chemokine expression profiles support the notion that particularly in heavily infiltrated primary MM lesions, Mig and to a lesser extent IP-10 are important mediators of an IFN-gamma-dependent pathway. Due to their lymphoattractant properties and the known inhibitory effects on the tumour vasculature, both chemokines may be critical for the control of local melanoma tumour growth.

Chemokine CXCL10↗

PubMed1993

Leukemic infiltration of the esophagus.

BACKGROUND: Leukemic infiltrates of the esophagus have been described occasionally in autopsy series, but there are no reports of antemortem diagnosis. METHODS: Case reports are presented for three patients with acute myeloid leukemia in whom leukemic infiltration of the esophageal mucosa was diagnosed histologically and cytologically by endoscopic examination. Autopsies of patients with leukemia from 1976-1988 were reviewed. RESULTS: The autopsy review of 207 patients with leukemia showed evidence of leukemic infiltration in the esophagus in 7.2% of cases. The only clinical factor identified to be significantly associated with esophageal involvement by leukemic cells was a high initial leukocyte count. Esophageal involvement was associated with leukemic infiltration of other soft tissues and organs. CONCLUSIONS: Although the etiology of dysphagia in patients with acute leukemia is usually related to infection, reflux, chemotherapy toxicity, or benign strictures, the frequency of esophageal leukemic infiltration in this autopsy series suggests that this diagnosis must be considered. Esophageal leukemia is usually associated with widely disseminated soft tissue and visceral infiltrates.

Adult↗

PubMed1995

Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia arising at the site of herpes zoster and herpes simplex scars.

BACKGROUND: Cutaneous lymphoid infiltrates at sites of herpes zoster scars in patients with B-cell chronic lymphocytic leukemia (B-CLL) often are diagnosed as benign lymphoid hyperplasia ("pseudolymphomas"). The histologic and immunophenotypic features of these lesions are not well characterized. Appearance of skin lesions in B-CLL patients is considered a poor prognostic sign. METHOD: Eight punch biopsies from five patients (three males, two females; mean age, 66.7 years) affected by B-CLL and presenting with lesions at sites of previous herpes simplex (upper lip, one patient) or herpes zoster (trunk, four patients; forehead, one patient) infections were included in the study. Histologic examination was performed on routine sections stained with hematoxylin and eosin and Giemsa. Immunohistologic stainings were performed with a standard three-step immunoperoxidase technique on formalin fixed, paraffin embedded tissue sections. RESULTS: Specific cutaneous infiltrates of B-CLL were diagnosed histopathologically and immunophenotypically in eight biopsies from all five patients. Clinically, patients presented with erythematous papules or plaques confined to the area of previous herpes virus eruptions. Histopathologic features in most cases were characterized by a variably dense perivascular and periadnexal infiltrate of small hyperchromatic lymphocytes throughout the entire dermis, reaching the subcutaneous fat. In one case, a dense, diffuse infiltrate involving the entire dermis was observed. A granulomatous reaction with presence of epithelioid and multinucleated giant cells was a prominent feature in four biopsies from three patients. Light areas containing large lymphoid cells with features of prolymphocytes and paraimmunoblasts (so-called "proliferation centers") could be observed only in the case characterized by a diffuse infiltrate. Immunohistology revealed an aberrant CD20+/CD43+ phenotype of neoplastic B cells, which is not found in normal B lymphocytes (CD20+/CD43-). Reactive T lymphocytes were present in all lesions and had a normal CD20-/CD43+/CD45Ro+ phenotype. At the time of this writing, four patients were alive without signs of skin disease after a mean follow-up of 58.5 months, and one patient died of B-CLL 24 months after the cutaneous eruption. CONCLUSIONS: Specific cutaneous infiltrates of B-CLL are not uncommon at sites of herpes virus scars. The diagnosis can be confirmed by histopathologic and immunophenotypic criteria. The prognosis is better than previously reported.

Aged↗

PubMed1996

HLA class I expression on human ovarian carcinoma cells correlates with T-cell infiltration in vivo and T-cell expansion in vitro in low concentrations of recombinant interleukin-2.

This study was carried out to determine whether HLA class I or class II expression on ovarian tumor cells and lymphocytic infiltration of the epithelial ovarian carcinoma (EOC) tissues were responsible for the ability to expand tumor-infiltrating lymphocytes (TIL) in vitro in low concentrations of recombinant interleukin-2 (rIL-2). Immunohistochemical analysis was performed using monoclonal antibodies that recognize framework determinants of either HLA class I or HLA class II or leukocyte differentiation antigens (LCA, CD3, CD4, and CD8). Cryostat sections of EOC had HLA class I and HLA class II expression on at least 5% of tumor cells in 18 of 20 specimens (90%). From another portion of the same tumor specimens T-cell lines were developed from TIL in low concentrations of rIL-2 (200-600 IU/ml) in 7 of 17 patients. Tumors from which TIL were expanded in vitro with rIL-2 had significantly higher proportions of HLA class I-positive tumor cells (73 +/- 10%) compared to tumors from which TIL failed to grow (40 +/- 10%) (P = 0.036). However, there was no difference in the proportions of HLA class II-positive tumor cells between the two groups. Tumor specimens of patients whose TIL were expanded in rIL-2 had significantly higher numbers per field (423 +/- 114 vs 154 +/- 20; P = 0.005) and proportions (90 +/- 3% vs 77 +/- 4%; P = 0.023) of infiltrating CD3+ cells, significantly higher numbers per field (115 +/- 44 vs 19 +/- 5; P = 0.003) and proportions (25 +/- 5% vs 11 +/- 2%; P = 0.017) of CD8+ cells and significantly higher numbers per field of CD4+ cells (318 +/- 101 vs 113 +/- 18; P = 0.025), in comparison to tumor specimens from patients whose TIL did not grow in vitro. Significant correlations were observed between the proportions of HLA class I-positive EOC tumor cells and the numbers of infiltrating LCA-positive cells (r = 0.67; P = 0.005) CD3+ cells (r = 0.70; P = 0.002), CD4+ cells (r = 0.69; P = 0.003), and CD8+ cells (r = 0.82; P = 0.001). The proportions of HLA class II-positive tumor cells correlated positively (r = 0.45; P = 0.049) only with the numbers of CD8+-infiltrating cells. In conclusion, we report here that HLA class I expression on EOC cells correlates with T-cell infiltration in vivo and T-cell expansion in vitro, in low concentrations of rIL-2.

Adult↗

PubMed2005

Morphological appearance, content of extracellular matrix and vascular density of lung metastases predicts permissiveness to infiltration by adoptively transferred natural killer and T cells.

We have recently shown that adoptively transferred, IL-2-activated natural killer (A-NK) cells are able to eliminate well-established B16-F10.P1 melanoma lung metastases. However, some B16-F10.P1 lung metastases were resistant to infiltration by the A-NK cells and also resistant to the A-NK cell treatment. The infiltration-resistant (I-R) B16-F10.P1 metastases had a unique "compact" morphology compared to the "loose" morphology of the infiltration-permissive (I-P) metastases. Here, we show that I-P loose tumors and I-R compact tumors are also found in lung metastases of mouse Lewis lung carcinoma (3LL), MCA-102 sarcoma, and MC38 colon carcinoma as well as rat MADB106 mammary carcinoma origin. Furthermore, the infiltration resistance of the compact tumors is not restricted to A-NK cells, since PHA and IL-2 stimulated CD8+ T-cells (T-LAK cells) also infiltrated the compact tumors poorly. Analyses of tumors for extracellular matrix (ECM) components and PECAM-1(+) vasculature, revealed that the I-R lesions are hypovascularized and contain very little laminin, collagen and fibronectin. In contrast, the I-P loose tumors are well-vascularized and they contain high amounts of ECM components. Interestingly, the distribution pattern of ECM components in the I-P loose tumors is almost identical to that of the normal lung tissue, indicating that these tumors develop around the alveolar walls which provide the loose tumors with both a supporting tissue and a rich blood supply. In conclusion, tumor infiltration by activated NK and T cells correlates with the presence of ECM components and PECAM-1(+) vasculature in the malignant tissue. Thus, analysis of the distribution of ECM and vasculature in tumor biopsies may help select patients most likely to benefit from cellular adoptive immunotherapy.

Adoptive Transfer↗

PubMed1999

Immunohistochemical analysis of lymphocytic infiltration in the tumor microenvironment in patients operated on for laryngeal cancer.

The aim of this study was to evaluate semiquantitative and qualitative analysis of lymphocytic infiltrations in a neoplasm microenvironment in patients with laryngeal cancers and the correlation analysis between the intensitivity degree and composition of lymphocytic infiltration in foreseeing a survival time and probability of the appearance of lymph node metastases. Postoperative specimens from 43 patients (Upper Silesia region) operated on for laryngeal cancer in the 2nd ENT Department, Silesian Medical University in Zabrze between 1985 and 1995 all had unfavorable courses due to tumor recurrences. The patients' ages ranged from 39 to 79 years (mean 57 years). Tissue specimens were subjected to routine processing. The degree of pathological changes was ascertained and immunohistochemical preparations of laryngeal tissue were prepared according to generally accepted methods. The following primary monoclonal antibodies were used: CD 3, CD 20, CD 43, CD 45 RO, CD 56. The distribution analysis of the intensity of the phenotype CD 43 evaluated the lymphocytic infiltration in relation to differentiation of the whole study group. The intensity of CD 43 cell infiltration increased in the group of patients with lymph node metastases. In patients with stage IV disease, a relationship was found between survival time and intensity of cell infiltrations with CD 43 and CD 45 RO lymphocytes. The influence of these two lymphocyte phenotypes in the patient subgroups - one after total laryngectomy with confirmed lymph node metastases and the other group without lymph node metastases - showed their prognostic value. Our analysis of lymphocytic infiltration, mostly of CD 43 cells, in the neoplasm microenvironment indicated a prognostic value for determining a shorter survival time and the possibility of lymph node metastases in patients with recurrences of cancer.

Adult↗