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Results for “Infiltrative”

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PubMed1996

[Soluble interleukin-2 receptor and macrophage colony-stimulating factor (M-CSF) in cerebrospinal fluid in patients with hematological malignancies: clinical significance in adult T-cell leukemia with meningeal infiltration].

We measured soluble interleukin-2 receptor (sIL-2R) and macrophage colony-stimulating factor (M-CSF) levels in the cerebrospinal fluid (CSF) of patients with hematological malignancies with or without meningeal infiltration and meningitis. Levels of sIL-2R and M-CSF in the CSF of adult T-cell leukemia (ATL) patients with meningeal infiltration were significantly higher than those of ATL patients without meningeal infiltration and non-ATL patients with meningeal infiltration. There was a significant positive correlation between sIL-2R levels and numbers of mononuclear cells in CSF of ATL patients with meningeal infiltration. However, M-CSF levels did not correlate with numbers of mononuclear cells. There was no correlation between CSF and serum levels of sIL-2R. There was also no correlation between sIL-2R and M-CSF in the CSF. Therefore, sIL-2R and M-CSF levels in the CSF may be useful in the diagnosis of meningeal infiltration in patients with ATL. In particular sIL-2R may be a sensitive marker.

Biomarkers, Tumor↗

PubMed1996

The inflammatory infiltrate in giant cell arteritis selects against B lymphocytes.

OBJECTIVE: To understand mechanisms regulating the cellular composition of the inflammatory infiltrate in giant cell arteritis (GCA) and to explore whether B lymphocytes, such as neoplastic B cells in chronic lymphocytic leukemia (CLL), can infiltrate the inflamed arterial wall of GCA. METHODS: A Mayo Clinic database search was conducted to identify patients that developed GCA after the onset of CLL between 1950 and 1994. Inflammatory infiltrates were analyzed immunohistochemically for T cells, B cells, and plasma cells. RESULTS: Five patients with CLL were identified who subsequently developed clinical findings suggestive of GCA. Three of the 5 patients had biopsy proven disease, presented with typical clinical and histomorphological features of GCA, and responded promptly to corticosteroid treatment. Leukemic B cells known for their ability to diffusely seed organs were absent in the inflammatory lesions in the temporal artery. Plasma cells that contribute to the vasculitic infiltrate in patients without CLL were markedly reduced in the GCA lesions of patients with CLL. Two other patients had symptoms suggestive of GCA. Their temporal artery specimens were remarkable for small adventitial lymphocytic infiltrates but lacked typical panarteritis. CONCLUSION: The inflammatory infiltrate of GCA is tightly regulated, and cell accumulation in the granulomas is an active, not a passive, mechanism. The inflammatory pathway in GCA is focused on T cells and macrophages and excludes B cells.

Antibodies, Monoclonal↗

PubMedDate not supplied

Immunophenotypic characterization of human primary and metastatic melanoma infiltrating leukocytes.

During a systematic screening of melanoma infiltrating mononuclear and polynuclear immunological effector cells we employed 10 well characterized monoclonal antibodies, directed against leukocyte differentiation antigens, and the alkaline phosphatase conjugated, indirect, streptavidinbiotin immunocytochemical antigen detection technique and when necessary, the recently developed antigen retrieval method to enhance the intensity of the immunoreactivity to characterize the heterogeneous infiltrate of human primary (n = 30) and metastatic (n = 10) melanomas. Our study is the first to employ formalin fixed, paraffin embedded tissue sections in seeking to determine the ex vivo presence of tumor infiltrating leukocytes, including T lymphocytes, in human melanomas. We established the presence of some type of melanoma infiltrating host's immunological effector cells in all 40 observed melanoma cases'. More specifically, we found NK cells, macrophages and granulocytes in 30 out of 30 PMs and 10 out of 10 MMs. These effector cells represented the vast majority (> 80%) of the melanoma infiltrating immunocompetent cells. T lymphocytes were observed in 20 out of 30 PMs and 6 out of 10 MMs, but their numbers represented only between 5% to 10% of the heterogeneous leukocytic infiltrate. B cells were found in 22 out of 30 PMs and 8 out 10 MMs, their numbers representing less than 5%. Presence of cells of the dendritic reticulum, involved in antigen presentation was not determined in any of the observed PMs and MMs. There were more than enough macrophages and neutrophils, cells which are deeply involved in antigen presentation and, as previously mentioned, we found these cells within the melanomas. Thus defective antigen presentation cannot be the reason for the small proportion of T lymphocytes. What is to blame is probably the increased dedifferentiation of the melanoma immunophenotype (IP) to a degree that MHC class I molecules and the antigens complexed with them are lost and therefore there is nothing to be recognized by the T lymphocytes. In view of these results it is our-opinion that following the initial non-specific immune reaction, which may not be tumor specific, the specific immune response of effector T cells takes over. After significant IP changes by the majority of melanoma cells, including the internalization or shedding of MHC class I antigens, these highly specialized cells are no longer effective and the immune system responds by causing the reappearance of NK cells, macrophages and granulocytes. Thus, the relationship between melanoma and the host's immune system is evolutionarily dynamic: changes are readily made by either side when necessitated.

Antibodies, Monoclonal↗

PubMed1996

[Differentiation of lupus erythematosus and lymphocytic infiltration].

Lymphocytic infiltration and lupus erythematosus have many features in common. The main distinguishing factor is the lack of epidermal involvement in lymphocytic infiltration, as compared to the frequent presence of epidermal changes in discoid lupus erythematosus. Other factors claimed to differentiate between both conditions are lack of antinuclear antibodies, negative immunofluorescence findings, and the more frequent presence of plasmacytoid monocytes in lymphocytic infiltration. To evaluate the significance of those findings, we studied cases of lymphocytic infiltration and lupus erythematosus with and without epidermal changes, using the same set of clinical, histopathological, and immunological criteria. No differences were found between lymphocytic infiltrates in cases with and without epidermal involvement. Based on those findings, lymphocytic infiltration seems to be a morphological variant of lupus erythematosus, rather than a distinct entity.

Diagnosis, Differential↗

PubMedDate not supplied

Local anaesthetic infiltration prior to arterial puncture for blood gas analysis: a survey of current practice and a randomised double blind placebo controlled trial.

BACKGROUND: Infiltration with local anaesthetic (LA) is recommended before arterial puncture (AP) for blood gas analysis. A telephone survey of 100 junior hospital doctors established that 84% never used LA; the reason for this cited by 47% of doctors was that they considered the injection to be as painful as AP itself. We therefore undertook a randomised double blind placebo controlled trial to establish whether the recommendation for LA is justified. METHODS: Patients undergoing AP were randomly allocated to one of three groups before arterial stab: A--Infiltration with 2% lignocaine; B--Infiltration with normal saline; C--No infiltration. Patient and doctor then rated the discomfort of the procedure. RESULTS: Both patients and doctors rated the pain of AP less when LA was used. Infiltration with LA was no more painful than with placebo. AP was no more difficult following LA as assessed by passes made, times skin broken and the doctor's rating of the procedure. CONCLUSION: This study supports the recommendation that LA should be infiltrated before radial artery puncture is performed. The belief that the use of LA makes the procedure more difficult and is as painful as arterial puncture should be dispelled.

Anesthesia, Local↗

PubMedDate not supplied

Association of mast cells with fibrosis and fatty infiltration in the minor salivary glands of patients with Sjögren's syndrome.

OBJECTIVE: To determine the distribution and density of mast cells in the minor salivary glands of patients with primary Sjögren's syndrome (pSS) and of normal controls. METHODS: Minor salivary gland biopsies were obtained from 19 patients with pSS, 9 with systemic lupus erythematosus, one each with rheumatoid arthritis, sarcoidosis, and Hodgkin's disease, and from 10 individuals who had subjective xerostomia with normal salivary gland biopsies. Biopsy specimens were evaluated for the degree of inflammation according to Tarpley's classification. Sections were analysed for staining with Toluidine blue and with the mast cell specific marker c-kit. The data obtained were correlated with the histological findings of fatty infiltration, fibrosis and lymphocytic infiltration. RESULTS: There was a significant correlation between the number of mast cells identified and the degrees of fibrosis and fatty infiltrates. There was no correlation between the intensity of lymphoid infiltration and the number of mast cells. c-kit staining showed a high correlation when compared to Toluidine blue staining. CONCLUSION: Mast cells in the minor salivary glands of patients with pSS are strongly associated with fibrosis and cell acid infiltration. However, there is no correlation with parameters of disease activity such as lymphoid infiltration.

Adipose Tissue↗

PubMed1997

[Comparison of the analgesic efficacy of EMLA 5% cream and lidocaine infiltration for biopsy of the genital mucosa].

OBJECTIVE: To compare the analgesic efficacy of EMLA 5 p. 100 cream versus Xylocaïne 1 p. 100 infiltration for biopsies of the genital mucosa. PATIENTS AND METHODS: 63 adult patients were randomized. EMLA (0.3-5 g) was applied during 7-12 minutes, and Xylocaïne 1 p. 100 (0.2-5 ml) was infiltrated 0-10 minutes before biopsy. Pain during the anaesthetic procedure and the biopsy was assessed by the patient using a Visual Analogue Scale. RESULTS: Pain scores were significantly lower with EMLA application than Xylocaïne infiltration, but infiltration resulted in better surgical anaesthesia. The combined pain scores (anaesthetic procedure and biopsy) were lower in the EMLA group, but this difference failed to reach statistical significance. CONCLUSION: EMLA is a less painful anaesthetic procedure than infiltration, but has a lower analgesic efficacy. EMLA can be used as an alternative to infiltration for biopsies of the genital mucosa.

Adult↗

PubMed1998

Comparison of local infiltration of tenoxicam and intravenous tenoxicam for postoperative analgesia in herniorrhaphy.

BACKGROUND: The major complaint of herniorrhaphy is postoperative pain which occurs during the first 24 h after operation. Tenoxicam has a long half-life of 60-80 h. Local infiltration of the drug concentrates the pain control effects in the local area. The local infiltration dose can be smaller than the recommended systemic dose needfully to reach the target area to be effective. Therefore we studied the effect of preoperative local infiltration of tenoxicam on postoperative pain. METHODS: Sixty patients, belonging to ASA classes I and II, undergoing unilateral herniorrhaphy, were randomly assigned to 4 groups. General anesthesia was induced with thiamylal 5 mg/kg, fentanyl 2 micrograms/kg, and atracurium 5 mg/kg. Group 1 (G1) patients were preoperatively injected with 10 mg of tenoxicam in 10 ml normal saline or distilled water, in the operative area. Group 2 (G2) and Group 3 (G3) patients were preoperatively given intravenous tenoxicam, 20 mg and 10 mg, respectively. Group 4 (G4) patients were not given preoperative local infiltration or intravenous tenoxicam to serve as control group. The pain score was assessed at 2 h, 9 h, 24 h postoperatively in all groups. We recorded the total amount of acetaminophen used and the form of administration of the analgesic drug. All patients received general anesthesia in uniform technique. RESULTS: Pain score and amount of analgesic drug required in G1 (local infiltration group) patients were significantly decreased compared with the other groups. The postoperative pain score of Visual Analog Scale (VAS) and analgesic requirement in the four groups were ranked as follows: G1 < G2 < G3 < G4. No significant difference was observed between G2, G3 and G4. Only the pain score in G2 patients significantly decreased (p < 0.05) during the late postoperative period (24 h) when compared with G4 patients. CONCLUSIONS: Preoperative local infiltration of tenoxicam can decrease postoperative pain score significantly during the most painful period (24 h) in herniorrhaphy.

Adult↗

PubMed1992

Administration of a prostaglandin synthetase inhibitor associated with an increased immune cell infiltrate in squamous cell carcinoma of the head and neck.

Squamous cell carcinoma of the head and neck produces a prostaglandin, PGE2, a potent inhibitor of cellular immune responses. We tested the effects of prostaglandin synthetase inhibition on the infiltration of squamous cell carcinoma of the head and neck with host lymphocytes. Tumor tissue samples were obtained from six patients (age range, 51 to 72 years) who presented with squamous cell carcinoma of the head and neck before and after 14 days of treatment with indomethacin (50 mg administered orally three times a day). Tumor-infiltrating immune cells were assayed in frozen tissue samples by indirect immunofluorescence. An eightfold increase in CD2+ lymphocytes compared with pretreatment tissue was observed. The number of CD4 and CD8 lymphocytes increased similarly. CD57 lymphocytes increased 15-fold and CD11b cells increased 11-fold. No infiltrating B-cell populations were evident. Double-labeling studies revealed that the mononuclear cells were located outside blood vessel walls, indicating that they had infiltrated the tumor parenchyma. Our findings demonstrate that the administration of indomethacin is associated with the increased immune cell infiltration of squamous cell carcinoma of the head and neck. This suggests that inhibition of PGE2 synthesis as it occurs in the tumor and or systemically may contribute to the homing of mononuclear cells to the tumor. These data suggest a mechanism to account for the clinical response to indomethacin previously reported in squamous cell carcinoma.

Aged↗

PubMed1998

Clinicopathological study on hepatocellular carcinoma with lymphocytic infiltration.

We examined the clinicopathologic features of 11 surgically resected hepatocellular carcinomas (HCCs) less than 3 cm in diameter with marked inflammatory cell infiltration (LHCCs). In comparison with the other 152 HCCs without such an infiltration (controls), there were no significant differences in male/female ratio, age, serum alpha-fetoprotein levels, and laboratory and imaging findings. All the 11 LHCC cases were hepatitis B surface antigen (HBsAg) negative and hepatitis C virus antibody positive. Among the 152 controls, 116 cases were also HBsAg negative and HCVAb positive and were referred to as HCV-only controls. The clinical features were not significantly different between the LHCC and the HCV-only controls. The LHCC group tended to have higher numbers of lymphocytes and monocytes in pre- and post-operative peripheral blood, but there were no significant group differences. Recurrence rate was 9.1% in the LHCC group, 47.7% in the controls and 47.5% in the HCV-only controls (P < .01). Five-year survival rate was 100% in the LHCC group, 65.1% in the controls and 68.1% in the HCV-only controls (P < .01). Histologically, remarkable inflammatory cell infiltration, mostly lymphocytic, was observed in the cancerous tissue of the LHCC group. Varying degrees of piecemeal necrosis of cancer nests produced by infiltrating lymphocytes were observed in all the 11 cases. Lymph follicle formation was also found in 10 of 11 cases (90.9%). Liver cirrhosis was associated in 6 LHCC cases (54.5%), in 117 control cases (77.0%), and in 91 HCV-only controls (78.4%). Tumor invasion into the portal vein in the vicinity of the tumor was found in 1 LHCC case (9.1%), in 54 controls (35.5%), and in 34 HCV-only controls (29.3%). Immunohistochemically, most of the infiltrating lymphocytes, other than those in the lymph follicle, were identified as T lymphocyte, and CD8+ T lymphocyte was more predominant than CD4+ T lymphocyte. Better prognosis of the LHCC group could attribute to the anti-tumor effect induced by cellular immunity of CD8+ and CD4+ T lymphocytes, and partly by humoral immunity of B cells which formed lymph follicles.

Adult↗

PubMed2006

Infiltration of tumor-reactive transforming growth factor-beta insensitive CD8+ T cells into the tumor parenchyma is associated with apoptosis and rejection of tumor cells.

BACKGROUND: TGF-beta is a potent immunosuppressant. High levels of TGF-beta produced by cancer cells have a negative inhibition effect on surrounding host immune cells and leads to evasion of the host immune surveillance and tumor progression. In the present study, we report a distinct ability of tumor reactive, TGF-beta-insensitive CD8+ T cells to infiltrate into established tumors, secrete relevant cytokines, and induce apoptosis of tumor cells. METHODS: CD8+ T cells were isolated from the spleens of C57BL/6 mice, which were primed with irradiated mouse prostate cancer cells, the TRAMP-C2 cells. After ex vivo expansion, these tumor reactive CD8+ cells were rendered TGF-beta-insensitive by infection with a retroviral (MSCV)-mediated dominant negative TGF-beta type II receptor (TbetaRIIDN). Control CD8+ cells consist of those transfected with the GFP-only empty vector and naïve CD8+ T cells. Recipient mice were challenged with a single injection of TRAMP-C2 cells 21 days before adoptive transfer of CD8+ T cells was performed. Forty days after the adoptive transfer, all animals were sacrificed. The presence of pulmonary metastases was evaluated pathologically. Serial slides of malignant tissues were used for immunofluorescent staining for different kinds of immune cell infiltration, cytokines, and apoptosis analysis. RESULTS: Pulmonary metastases were either eliminated or significantly reduced in the group receiving adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells (3 out of 12) when compared to GFP controls (9 out of 12), and naïve CD8+ T cells (12 out of 12). Results of immunofluorescent studies demonstrated that only tumor-reactive TGF-beta-insensitive CD8+ T cells were able to infiltrate into the tumor and mediate apoptosis when compared to CD4+ T cells, NK cells, and B cells. A large amount of cytokines such as perforin, nitric oxide, IFN-gamma, IL-2, TNF-alpha were secreted in tumor tissue treated with tumor-reactive TGF-beta-insensitive CD8+ T cells. No immune cells infiltration and cytokine secretion were detected in tumor tissues treated with naïve T cells and GFP controls. CONCLUSIONS: Our results demonstrate the mechanism of anti-tumor effect of tumor-reactive TGF-beta-insensitive CD8+ T cells that adoptive transfer of these CD8+ T cells resulted in infiltration of these immune cells into the tumor parenchyma, secretion of relevant cytokines, and induction of apoptosis in tumor cells. These results support the concept that tumor-reactive TGF-beta-insensitive CD8+ T cells may prove beneficial in the treatment of advanced cancer patients.

Animals↗

PubMed2001

Suppressive effects of histamine H1 receptor antagonist diphenhydramine on the leukocyte infiltration during endotoxin-induced uveitis.

Histamine has been shown to play an important role in the step of leukocyte rolling, the initial step to leukocyte infiltration into an inflamed region. We investigated the roles of histamine in the leukocyte recruitment during endotoxin-induced uveitis (EIU) in vivo using acridine orange digital fluorography. An injection of histamine into the vitreous cavity of a Lewis rat induced leukocyte rolling along the major retinal veins. In other experiments, EIU was induced in Lewis rats by footpad injection of lipopolysaccharide (LPS). Leukocyte rolling was also observed in the retinal veins of EIU rats. To block the histamine H1 receptor, diphenhydramine (DPH) was administered intraperitoneally 15 min before the LPS injection. DPH significantly inhibited leukocyte rolling along the major retinal veins of EIU rats, suppressing leukocyte infiltration into the vitreous cavity. The vasodilation in EIU was also significantly suppressed with DPH. Moreover, leukocyte infiltration into aqueous humor was significantly suppressed in DPH-treated rats. Although the inhibitory effects of DPH was less obvious at later time points, addition of DPH every 12 hr showed prolonged anti-inflammatory effects up to 48 hr after LPS injection. In contrast, protein leakage into the aqueous humor was not suppressed as much as leukocyte infiltration with DPH. These results suggest that histamine would play a pivotal role in leukocyte recruitment during EIU in rats. Blocking the histamine H1 receptor might help to prevent or minimize leukocyte infiltration in uveitis.

Animals↗

PubMed1996

HLA expression and tumor-infiltrating immune cells in uveal melanoma.

BACKGROUND: In uveal melanoma, both the amount of tumor-infiltrating cells and the level of expression of HLA antigens are quite variable. We hypothesized that low levels of HLA expression lead to a lack of antigen presentation, which might prevent proper immunologic recognition of the tumor. This lack of recognition might subsequently lead to low levels of tumor-infiltrating cells. METHODS: To test this hypothesis, we determined the type and number of tumor-infiltrating cells in tumor sections from 24 uveal melanomas. We applied monoclonal antibodies directed against different types of immune cells and compared the results with the expression of HLA class I and class II antigens on the tumor cells. RESULTS: Infiltrating immune cells were observed in all uveal melanomas (although in small amounts), with a predominance of T lymphocytes. Significant positive correlations were observed between the number of CD3+ cells (T lymphocytes) and monomorphic HLA class I expression, allele-specific HLA-A2 and Bw4 expression, and HLA class II expression. Furthermore, the number of CD4+ cells (T helper cells, monocytes/ macrophages) and of CD11b+ cells (monocytes/macrophages) was significantly correlated with the level of monomorphic HLA class I expression. CONCLUSION: These data support our hypothesis that low levels of HLA expression (and therefore a lack of presentation of tumor-specific antigens) may lead to a low level of tumor infiltrate.

Adult↗

PubMedDate not supplied

Spontaneous regression of human melanoma/nonmelanoma skin cancer: association with infiltrating CD4+ T cells.

Spontaneous regression occurs in some human malignant melanomas and basal cell carcinomas (BCCs). We have compared the cellular infiltrate in regressing and nonregressing tumors in order to analyze the mechanism by which regression occurs. Regressing primary melanomas and BCCs were infiltrated with a larger number of CD4+, but not CD8+, T lymphocytes than were seen in nonregressing tumors. The number of interleukin 2 receptor-positive (early activation marker) but not transferrin receptor-positive (intermediate activation marker) T cells was increased, indicating that the infiltrating T cells were activated. Large numbers of Langerhans cells, macrophages, and other class II major histocompatibility complex (MHC)-expressing cells were present but were not increased in the regressing tumors. There were no detectable B lymphocytes, and the regressing tumor cells displayed levels of HLA-DR expression similar to those of the nonregressing tumors. Comparison of squamous cell carcinoma (SCCs) with keratoacanthomas (KAs), which are likely to be a spontaneously regressing form of SCC, also showed increased infiltration of activated CD4+, but not CD8+, T cells within the KA. A murine ultraviolet (UV)-induced squamous tumor that spontaneously regresses when transplanted into immunocompetent syngeneic mice was also infiltrated with increased numbers of activated CD4+, but not CD8+, T cells prior to and during rejection. These results indicate that spontaneous regression of human skin tumors is likely to be immunologically mediated, and that CD4+ T lymphocytes seem to mediate this regression.

Animals↗

PubMed1992

Immunohistochemical analysis of lymphocyte subsets infiltrating gastric carcinoma after mitomycin C administration.

The intensity of lymphoid cell infiltration and distribution of lymphocyte subsets in tumors were investigated immunohistochemically on tumor tissues obtained from 11 patients with gastric carcinoma, who had been treated with mitomycin C (MMC), 12 mg/m2, i.v. 5 days before operation. The results were compared with those obtained from 24 untreated patients as controls. In the tumor tissues from pretreated patients, the intensity of lymphoid infiltration was not significantly different from that of untreated patients. However, high-grade infiltration of CD4+ cells was observed in 55% of pretreated patients, whereas only 8% of control patients exhibited the high-grade infiltration (P < 0.02). Since the CD8+ cell infiltration was not significantly altered, the ratio of CD4+ to CD8+ cells was more frequently estimated to be more than 1 in patients pretreated with MMC, as compared to untreated controls (P < 0.02). Further, CD25+ cells in pretreated tumor tissues were more predominant than those in control tumor tissues (P < 0.05). These results suggest that MMC administration induces these alterations in lymphocyte subsets in tumor tissue in patients with gastric carcinoma.

Aged↗

PubMed2005

Tumor-infiltrating B cell immunoglobulin variable region gene usage in invasive ductal breast carcinoma.

A major focus of tumor immunology is to reveal the potential role and capacity of immunocompetent cells found in different solid tumor tissues. The most abundant infiltrating cells (TIL), the T lymphocytes have been investigated in details concerning T-cell receptor usage and specificity. However, B cells have hardly been investigated in this respect, although high cellular B-cell infiltration has been correlated with improved patients' survival in some breast carcinomas. This led to our objectives to study variable region gene usage of the tumor-infiltrating B cells in different breast carcinoma types. By defining the immunoglobulin repertoire of the tumor-infiltrating B lymphocytes in the most common invasive ductal carcinoma (IDC) of the breast we compared it to the rare medullary breast carcinoma (MBC). After phenotyping infiltrating ductal carcinomas, B cells were obtained from tumor tissue by microdissection technique. Numerous rearranged TIL-B immunoglobulin heavy chain V genes (VH) were amplified, cloned, sequenced, and comparatively analyzed. Some characteristics were found for both breast carcinoma types. The immunoglobulins produced by TIL-B in ductal carcinoma are highly matured and oligoclonal. We conclude that Ig variable region gene usage reveals similar and distinguishable characteristics of TIL-B immunoglobulin repertoires, which are representative of the nature of the immune responses in invasive ductal and medullary breast carcinomas.

B-Lymphocytes↗

PubMed2003

A basal membrane-like structure surrounding tumour nodules may prevent intraepithelial leucocyte infiltration in colorectal cancer.

Epithelial tumours consist of an epithelial compartment and a stromal compartment, which are sometimes separated by a basal membrane-like structure. We sought to determine whether these factors have prognostic value in 84 curatively resected stage II and III colorectal cancer by immunohistochemically staining tumours for leucocytes (CD45) and extracellular matrix, and to assess the presence of a basal membrane-like structure. Leucocyte infiltration was also assessed in hematoxylin-eosin (HE) stained sections. Most leucocytes were located in the tumour stroma. A relatively high intraepithelial leucocyte infiltration was significantly correlated with a lower level of tumour recurrence (P=0.03) and a longer disease-free survival (P=0.05), whereas leucocytes located in the tumour stroma (P=0.92) or at the advancing margin (p=0.06) were not. Intraepithelial leucocyte infiltration was also significantly correlated with leucocyte infiltration in the tumour stroma (P=0.02) and at the advancing tumour margin (P=0.005), and as assessed in HE-stained tumour sections (P=0.05), but each of these parameters on its own did not have a prognostic value in predicting disease-free survival. Moreover, the presence of a basal membrane-like structure surrounding the tumour epithelium was inversely correlated with the number of intraepithelial leucocytes (P=0.05), suggesting that this membrane-like structure functions as a barrier to intraepithelial leucocyte infiltration. We conclude that leucocytes must be in the direct vicinity of tumour cells to affect tumour growth. The presence of an extracellular matrix barrier seems to prevent this interaction.

Adult↗

PubMed1998

Molecular characterisation of tumour infiltrating lymphocytes in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is often associated with a lymphocytic infiltrate that is believed to represent an in vivo immune reaction to the tumour cells. In this study, the tumour-infiltrating lymphocytes (TIL) associated with primary OSCC were characterised molecularly in six newly-diagnosed patients to determine the nature of the immune response to the primary tumour. The primary tumours in three of the six patients were associated with a moderate to dense CD8+ T cell infiltrate whilst the cellular infiltrate in the other primary tumours was sparse. The CD3+ T cells were also HLA-DR+. In all cases, there were few CD56+ cells, suggesting that TIL were predominantly T cells bearing the alpha/beta T cell receptors (TCR). The TCR Vbeta repertoire of TIL in these six cases was analysed. TCR Vbeta gene usage by TIL was heterogeneous. A restricted usage of TCR Vbeta genes by TIL was evident in two tumours associated with a dense CD3+ T cell infiltrate. In one of these, there was histological evidence of tumour cell destruction by TIL. Further analysis of the predominant TCR Vbeta gene family used by TIL in this individual showed a unique in-frame nucleotide sequence in 100% of the transcripts. This recurrent transcript was not detected in the peripheral blood of this patient, indicating a local T cell clonal expansion in the vicinity of the tumour. Overall, these results suggest that activation and clonal expansion of T cells occurs and may play a role in local tumour destruction in OSCC.

Adult↗