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PubMed2003

The immunophenotype and activation status of the lymphocytic infiltrate in human breast cancers, the role of the major histocompatibility complex in cell-mediated immune mechanisms, and their association with prognostic indicators.

BACKGROUND: The aims of this study were to characterize, phenotypically, the immune infiltrate in human breast cancers, to assess the activation status of tumor-infiltrating lymphocytes (TIL), and to define the association of these findings with established prognostic indicators. METHODS: Immunohistochemistry was performed on frozen sections of 60 primary breast cancers by use of monoclonal antibodies to T lymphocytes (CD3), T-helper cells (CD4), cytotoxic T-cells (CD8), natural killer cells (CD56), interleukin-2 receptors (IL-2R), and major histocompatibility (MHC) class I antigen (HLA-ABC) and MHC class II antigen (HLA-DR). RESULTS: All tumors stained positive for CD3, CD4 and CD8, but with marked variation in the intensity of the infiltrate. In tumors with a moderate infiltrate of TIL, there was a trend toward a greater representation of T-helper cells. However, as the intensity of TIL increased, there was a decline in the proportion of T-helper cells and a concomitant rise in the relative proportion of cytotoxic T cells. There was a relative paucity of natural killer cells. A significant association was found between the intensity of TIL and the number of positive nodes (P=.02) and the intensity of the infiltrate of both T-helper cells and cytotoxic T cells with ER expression (P=.03 and.05, respectively). Most tumors stained positive for IL-2R. The expression of IL-2R was associated with the intensity of TIL (P<.0001), T-helper cells (P<.002), cytotoxic T cells (P=.01) and natural killer cells (P=0.04), and also with the degree of lymph node positivity (P=.02) and histologic tumor grade (P=.05). MHC class II expression was variable, and a large proportion of the tumors showed limited expression in individual cancer cells. There was an association between the expression of HLA-DR in tumor cells and the activation status of TIL (P=.03). CONCLUSION: An immune infiltrate is an invariable finding in breast cancers, and the intensity of the infiltrate is greater in node positive tumors. Additionally, TIL may well be activated, albeit partially, in most tumors, suggesting that cell-mediated immune mechanisms are functionally intact.

Breast Neoplasms↗

PubMed2001

Ocular manifestations of leukemia: leukemic infiltration versus infectious process.

OBJECTIVE: To determine whether specific guidelines can be developed to distinguish whether retinal infiltration in leukemia patients represents infection or neoplasia. DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS: Six patients recently seen at University of California San Francisco with retinal infiltrates in a setting of leukemia, for which adequate written and photographic information of disease course was available. INTERVENTION: Observation consisted of retrospective review of clinic charts, hospital medical records, and fundus photographs. MAIN OUTCOME MEASURES: Determination of whether retinal infiltrates represented neoplasia or infection was made by review of medical records. RESULTS: In this series, neoplastic retinal infiltrates were found in patients who had newly diagnosed leukemia and those who were in blast crisis. In contrast, the two patients who were in complete remission, but had undergone bone marrow transplantation, had retinal infiltrates attributable to infection. CONCLUSIONS: Every patient with retinal infiltrates in the setting of newly or previously diagnosed leukemia requires a systemic and central nervous system workup before the initiation of ophthalmologic treatment. The systemic status of the patient is highly informative in determining whether infection or neoplasia is responsible for the infiltration.

Adult↗

PubMed1997

Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis.

Local immunoregulation mediated by mononuclear tumour-infiltrating cells is considered of importance for tumour progression of colorectal cancer, although the balance between immunosuppressor and cytotoxic activities is unclear. Colorectal cancers from 26 patients were investigated using a panel of monoclonal antibodies in order to identify subsets of mononuclear inflammatory cells and to study their pattern of distribution in relation to tumour stage and cytotoxic immune reactivity against the tumour. In all but five tumours, mononuclear cells, lymphocytes or monocytes were present in fairly large numbers, particularly in the stroma. The infiltration of CD4+ mononuclear cells predominated over the CD8+ subset. Infiltration near the tumour cells was found in four cancers only. Stromal infiltration of CD11c+ macrophages was found in all but eight tumours. Small regressive areas, in which the histological architecture of the tumours was broken down, were found in 17 tumours with intense or moderate infiltration by CD4+ lymphocytes or CD11c+ macrophages. Probably this destruction of tumour tissue was caused by cytotoxic activity of the tumour-infiltrating mononuclear cells. In Dukes' class A and B tumours, CD4+ lymphocytes predominated over CD4+ cells with macrophage morphology, but the latter were increasingly found in Dukes' class C and D disease. The occurrence of MHC II-positive macrophages and lymphocytes in different Dukes' classes was similar to that of CD4+ cells. In contrast to this, CD11c+ and CD11a+ cells were more frequent in Dukes' A and B class tumours compared with Dukes' C and D. Four out of nine tumours of the latter stages showed a poor inflammatory reaction. The interpretation of our results is that the subsets of tumour-infiltrating mononuclear cells change with advancing Dukes' class and that the local immune control is gradually broken down in progressive tumour growth, even if some cytotoxic activity is still present.

Aged↗

PubMed2003

Lymphocytic infiltrates and subclinical epithelial tumor extension in patients with chronic leukemia and solid-organ transplantation.

BACKGROUND: Dense infiltrates in association with squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) in patients with underlying chronic lymphocytic leukemia (CLL) may complicate pathologic interpretation of histologic margins. OBJECTIVE: The study was conducted to determine the frequency of identifying dense inflammatory infiltrates in frozen histologic sections during Mohs operation for BCC or SCC in patients with CLL and organ-transplant recipients, to characterize the infiltrate (reactive versus leukemic) in CLL, and to estimate the subclinical tumor extension in patients with CLL, transplant recipients, and control subjects undergoing Mohs procedure. METHODS: Frozen sections of head and neck BCC and SCC obtained during Mohs procedures in patients with CLL, organ transplant recipients, and a control group were reviewed retrospectively. Biopsy specimens of CLL with dense infiltrates were assessed with immunohistochemical stains. Subclinical tumor extension (postoperative defect size minus preoperative tumor size) was evaluated in each group. RESULTS: Dense infiltrates were found in tumors of 20 of 55 patients with CLL (36%), 1 of 8 transplant recipients (13%), and 1 of 105 controls (1%). In patients with CLL, 75% of the dense infiltrates were B-cell leukemic. Compared with controls, the mean subclinical tumor extension was larger in patients with CLL (P=0.029) and in transplant recipients (P=0.55). CONCLUSION: Dense leukemic infiltrates associated with BCC or SCC in CLL may complicate pathologic interpretation of Mohs surgical histologic margins and may be associated with larger postoperative defects relative to preoperative clinical tumor appearance. In patients with CLL, as in transplant recipients, SCC seems more likely to develop than BCC.

Basal Cell Carcinoma↗

PubMed2003

A diagnosis of chronic lymphocytic leukemia prompted by cutaneous lymphocytic infiltrates present in mohs micrographic surgery frozen sections.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the United States. Patients with CLL are at an increased risk for the development of second malignant neoplasms, the most common of which is cuta-neous squamous cell carcinoma (SCC). Cutaneous infiltrates of CLL have been reported in association with primary cutaneous neoplasms, including SCC, basal cell carcinoma, and actinic keratosis. The finding of a dense lymphocytic infiltrate surrounding a cutaneous neoplasm should prompt consideration of possible underlying CLL. OBJECTIVE: To review the relationship of CLL to cutaneous SCC and to raise awareness of the possible coexistence of these two neoplasms. METHODS: The case report describes a patient with a SCC of the left cheek treated with Mohs micrographic surgery. A dense lymphocytic infiltrate was noted on the frozen sections, and a complete blood count was obtained. RESULTS: A lymphocytosis was detected, leading to the diagnosis of CLL, stage 0. CONCLUSION: Patients with CLL are at an increased risk for the development of cutaneous neoplasms. An infiltrate of leukemic cells in documented CLL patients can be associated with cutaneous neoplasms such as SCC. We present a patient with no known hematologic malignancy who demonstrated a dense lymphocytic infiltrate on Mohs sections. The diagnosis of CLL was considered based on the appearance of this infiltrate. Subsequently, a new case of CLL was confirmed with appropriate testing. The finding of a dense subcutaneous infiltrate of lymphocytes on Mohs frozen sections should raise the possibility of CLL and lead to appropriate screening tests.

Aged↗

PubMed1997

Treatment of metastatic renal cell carcinoma with nephrectomy, interleukin-2 and cytokine-primed or CD8(+) selected tumor infiltrating lymphocytes from primary tumor.

PURPOSE: Metastatic renal cell carcinoma is a disease with a mean survival of 6 to 10 months. Interleukin-2 (IL-2), the only approved therapy for metastatic renal cell carcinoma, is associated with a 14% response rate and durable remissions in some patients with high performance status. We performed a series of trials of IL-2 plus tumor infiltrating lymphocyte cell therapy and report the clinical results from 62 patients enrolled in these trials. MATERIALS AND METHODS: Patients were eligible if they had metastatic renal cell carcinoma with the primary tumor in place and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were treated with cytokines before nephrectomy and preparation of cytokine primed tumor infiltrating lymphocytes or CD8(+) tumor infiltrating lymphocytes were isolated for infusion into patients. Of 62 patients enrolled 55 were treated with tumor infiltrating lymphocytes and IL-2, and were evaluable for toxicity, response and survival. RESULTS: There were no postoperative mortalities. Of the patients 7 (11%) could not undergo systemic therapy. No unexpected IL-2 related toxicities or significant toxicities related to cell infusion were noted. Overall 5 patients (9.1%) achieved a complete response and 14 (25.5%) achieved a partial response. The responses were durable with a median duration of 14 months (range 0.8+ to 64+). The actuarial survival was 65% at 1 year and 43% at 2 years from the time of nephrectomy, with an overall median survival for all patients of 22 months (range 2 to 70+). The median survival for the responding patients has not yet been reached (range 2 to 63+). CONCLUSIONS: These results demonstrate that immunotherapy with radical nephrectomy, tumor infiltrating lymphocytes, and IL-2 provides substantial clinical benefit in the majority of patients. Component cellular therapy with enriched cell fractions allows the administration of a more standardized cell product. The present results with nephrectomy, tumor infiltrating lymphocytes and IL-2 are encouraging, and a randomized clinical trial of nephrectomy, CD8(+) tumor infiltrating lymphocytes, plus IL-2 versus nephrectomy and IL-2 alone is currently in progress.

Adult↗

PubMed1994

Elevated levels of soluble factors in the cerebrospinal fluid in patients with adult T-cell leukaemia complicated with meningeal infiltration.

We measured some soluble factors in the cerebrospinal fluid (CSF) of patients with adult T-cell leukaemia (ATL) complicated with meningeal infiltration. Interleukin-4 (IL-4) was not detectable in the CSF of all cases with meningeal infiltration. Interleukin-6 (IL-6) was detected in a few patients with ATL. Measurement of IL-4 and IL-6 in CSF had no diagnostic value for meningeal infiltration of ATL cells. Soluble CD4 (sCD4) was highly elevated in all ATL patients with meningeal infiltration. Soluble interleukin-2 receptor (sIL-2R; sCD25) in CSF was markedly elevated in 13/18 ATL patients (72.2%) with meningeal infiltration. Levels of sCD4 and sCD25 in the CSF of ATL patients with central nervous system (CNS) symptoms were significantly higher than those of non-ATL patients with CNS symptoms. These observations indicate that sCD4 and sCD25 in the CSF are probably associated with meningeal infiltration of leukaemia cells that expressed CD4 and CD25 on the surface membrane and new markers for the meningeal infiltration of ATL cells.

CD4 Antigens↗

PubMed1998

Prevalence of lymphocytic infiltrate in 1400 pituitary adenomas.

To evaluate the prevalence of lymphocytic infiltrate in a large series of pituitary adenomas, we retrospectively studied tumor tissues from 1400 patients. Based on immunocytochemical data, tumors were classified as PRL (n=411), multihormonal (n=310), immunonegative (n=275), ACTH (n=166), GH (n=137), alpha subunit (n=44), FSH and/or LH, (n=42), and TSH (n=15) adenomas. The lymphocytic infiltrate was diagnosed on histological examination and investigated by immunostaining with anti LCA (human leucocyte common antigen), anti CD45RO (human T cell) and anti CD20 (human B cell) antibodies. Lymphocytic infiltrate was present in 40 adenomas (2.9%), 26 females and 14 males, aged 18 to 77 years (mean+/-SD, 37+/-14 years). The tumors were 19 PRL, 8 multihormonal, 4 GH, 4 alpha subunit, 3 ACTH, and 2 immunonegative adenomas. In PRL adenomas, the sex ratio (female/male) and the age were similar in patients with and without lymphocytic infiltrate (2.8 vs. 4.6 and 29+/-6 years vs. 32+/-11 years, respectively). The frequency of lymphocytic infiltrate was similar in PRL, GH, ACTH and multihormonal adenomas, but lymphocytic infiltrate was significantly more frequent in PRL adenoma than in immunonegative adenoma, and in alpha subunit adenoma than in immunonegative, ACTH and multihormonal adenomas. The lymphocytic cells were almost exclusively T cells. We conclude that lymphocytic infiltrates are rare in pituitary adenomas. Their frequency is not statistically different in major categories of secreting adenomas (PRL, GH, ACTH, multihormonal). Their pathophysiological significance remains to be established.

Adenoma↗

PubMed1999

Cytotoxic phenotype of tumor infiltrating lymphocytes in medullary carcinoma of the breast.

Medullary carcinoma (MC) of the breast is considered to carry a more favorable prognosis than other subtypes of infiltrating ductal carcinoma This is a biological paradox because its clinical behavior contrasts with its anaplastic morphology. MC is characterized by a dense lymphocytic infiltrate. In this study, we determined the cytotoxic potential and activity of tumor infiltrating lymphocytes (TILs) in MC by CD3, CD8, TIA-1, and granzyme B immunostaining on paraffin-embedded sections. Fourteen cases of typical MC (TMC) and 15 cases of atypical MC (AMC) classified according to Ridolfi criteria, and 19 cases of poorly differentiated infiltrating ductal carcinoma (PDC) were studied. TILs were quantified separately into two groups: cells infiltrating tumor nests and cells within stroma The number of CD8+ and TIA-1+ cells infiltrating tumor cell nests were markedly increased in TMC and AMC, as opposed to the PDC subgroup (159.6+/-132.8; 77.4+/-59.3; 9.4+/-10.5 and 171.2+/-152.4; 72.3+/-55.0; 10.8+/-12.7 per high power field, respectively). The number of tumor infiltrating granzyme B+ cells was significantly greater in TMC and AMC, as compared with the PDC subgroup (82.1+/-64.9, 33.9+/-19.7, and 3.1+/-5.1, respectively). Although no significant difference was found between the number of stromal CD3+ and CD8+ lymphocytes among the three subgroups, stromal granzyme B+ cells were significantly elevated in TMC and AMC as compared with the PDC subgroup. Finally, the relative proportion of granzyme B+ as opposed to CD3+ intraepithelial and stromal lymphocytes was greater in TMC and AMC as compared with the PDC subgroup (0.52+/-0.29; 0.47+/-0.31; 0.19+/-0.18 and 0.18+/-0.11; 0.13+/-0.11; 0.06+/-0.05, respectively). The presence of increased numbers of activated cytotoxic lymphocytes in MC of the breast may be a key mechanism active in the host versus tumor response leading to improved prognosis.

Adult↗

PubMedDate not supplied

Controversies on the prognostic significance of tumor infiltrating leukocytes in solid human tumors.

We have performed immunophenotypical (IP) analyses of tumor infiltrating leukocytes (TIL) in both childhood brain tumors (medulloblastomas[MEDs]/primitive neuroectodermal tumors [PNETs] and astrocytomas [ASTRs]) and malignant melanomas (both primary and metastatic) employing a well-characterized library of monoclonal antibodies (MoABs) directed against leukocyte differentiation/activation associated antigens. The antigens were detected by an indirect, biotinstreptavidin conjugated alkaline phosphatase (AP) immunocytochemical technique. Our systematic cell-surface antigen expression profile analysis of 76 primary childhood brain tumors (34 MEDs/PNETs and 42 ASTRs) identified CD8+ CTL in 58/76 brain tumors. CD4+, MHC class II restricted helper lymphocytes were present in 65/76 brain tumors and represented 1-10% of the observed cells. Macrophages were present in 74/76 childhood brain tumor cases observed by us. Leukocyte common antigen (LCA) expression was demonstrated in all 76 brain tumors studied. MoAB UJ 308 detected the presence of premyelocytes and mature granulocytes in 60/76 brain tumors. They were localized perivascularly, within the tumor tissue, or close to necrotic regions. Natural killer (NK) cells were not defined in the childhood brain tumors observed in this study. The IP characteristics of the heterogeneous leukocytic infiltrate of 30 primary (PMs) and 10 metastatic melanomas (MMs) was also investigated by us. 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 30/30 PMs and 10/10 MMs. These effector cells represented the vast majority (> 80%) of the melanoma infiltrating immunocompetent cells. T lymphocytes were observed in 20/30 PMs and 6/10 MMs, but their numbers represented only between 5% to 10% of the heterogeneous leukocytic infiltrate. B cells were found in 22/30 PMs and 8/10 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. The notion that infiltration of the neoplastically transformed mass of cells by TIL is always a prognostically positive phenomenon has changed in recent years as research on extracellular matrix remodeling and angiogenesis have identified numerous secreted factors which are common to both neoplastically transformed cells and infiltrating leukocytes.

Brain Neoplasms↗

PubMed1992

The relationships among tumor-infiltrating lymphocytes, histopathologic findings, and long-term clinical follow-up in renal cell carcinoma.

The relative abundance of tumor-infiltrating mononuclear cells (TIM) was retrospectively evaluated by immunohistology in nephrectomy specimens from 24 cases of human renal cell carcinoma (RCC). The extent of T-lymphocyte (T-cell) and B-lymphocyte (B-cell) infiltration of the tumors was graded semiquantitatively (0 to 4) in each case. Results of this analysis were correlated with clinical evidence of recurrent RCC, histologic evidence of venous invasion, tumor necrosis, and histologic cell type. Clinical follow-up demonstrated the presence of recurrent tumors in four of the 24 cases (17%), and these cases correlated with higher stage and pathologic grade tumors, as well as significantly increased TIM. Venous invasional and tumor necrosis correlated directly with tumor size, pathologic grade, and extent of TIM. Venous invasion was also associated with advanced stage. The group of cases with mixed or granular histologic cell type was associated with advanced stage, high pathologic grade, and increased T-cell infiltration compared to the clear-cell group of tumors. Overall, the pathologic grade demonstrated the highest correlation coefficients with clinical and TNM stage, but also correlated directly with the extent of T-cell infiltration of the tumor. These results confirm previous findings demonstrating a correlation in RCC between increased T-cell infiltration and both high clinical stage and pathologic grade. In addition, increased T-cell infiltration was found to correlate with tumor recurrence, indicating that such infiltration, along with high pathologic grade, is another indicator of poor prognosis in RCC.

Aged↗

PubMed1993

Association between HLA-expression and infiltration of immune cells in cervical carcinoma.

BACKGROUND: To determine the degree of specificity of the cellular immune response in cervical carcinoma, that is known to be human papillomavirus-related, we investigated the exact relationship between in situ tumor-infiltrating immune cells and the monomorphic/allele-specific HLA expression on the tumor cells. EXPERIMENTAL DESIGN: Attention was focussed on the type, location and number of in situ immunocompetent cells in malignant cervical tissue (N = 30). Immune cell distribution was quantitatively assessed by morphometry for stromal and tumor tissue separately. These results were related to the degree of expression of monomorphic- and allele-specific HLA I and II antigens on the cervical tumor cells. RESULTS: In monomorphic HLA class I downregulated cervical tumors, a significant decrease in tumor-infiltrating CD8+ T cells was observed. However, allele-specific downregulation of respectively HLA-A2, HLA-A3, HLA-Bw4, and HLA-Bw6, did not correlate significantly with a decrease in tumor-infiltrating immune cells. For HLA class II-positive cervical tumors, HLA-DR expression significantly correlated with an increase in the presence of tumor-infiltrating CD3+/CD4+/CD8+ T cells, CD56+ natural killer cells and CD16+ macrophages. No significant correlations were found between alterations in HLA class I or II expression on the tumor cells and stromal infiltrating immune cells. CONCLUSIONS: Our observations provide in situ immunomorphologic evidence that in cervical carcinoma, de novo expression of HLA class II antigens on the tumor cells resulted in an increase of tumor-infiltrating immune cells. In addition, the tumor-infiltrating CD8+ T lymphocytes correlated with monomorphic HLA class I expression on the tumor cells, which stresses the existence of a HLA-restricted immune response of T lymphocytes in cervical carcinoma. These findings might have implications for the biologic behavior of this disease and have to be taken into account in strategies concerning immunotherapy of cervical carcinoma.

Carcinoma↗

PubMed1996

[Clinical significance of soluble interleukin-2 receptor levels in the cerebrospinal fluid in patients with adult T-cell leukemia complicated with meningeal infiltration].

We measured soluble interleukin-2 receptor (sIL-2R) levels in the cerebrospinal fluid (CSF) of patients with hematological malignancies especially, adult T-cell leukemia (ATL) and non-Hodgkin's lymphoma (NHL) with or without meningeal infiltration. CSF levels of sIL-2R were significantly higher in patients with ATL and NHL with meningeal infiltration than in patients with both diseases without meningeal infiltration. The sIL-2R levels in CSF were elevated in 4/4 ATL patients (100%) and 3/13 NHL patients (23%) with meningeal infiltration. CSF levels of sIL-2R from ATL patients with meningeal infiltration had a tendency to elevate in correlation with numbers of mononuclear cells and lactic dehydrogenase (LDH) in CSF. However, these had no correlation with serum levels of sIL-2R. Therefore, sIL-2 levels in CSF may be useful in the diagnosis of meningeal infiltration in patients with ATL, are probably specific markers for meningeal infiltration of ATL.

Adolescent↗

PubMed1995

[The relationship between the phenotype of tumor infiltrating cells and the prognosis in laryngeal cancer].

By using the method of immunohistochemical avidin-biotin-peroxidase complex (ABC), toluidine blue and HE staining, the infiltrated grade and dispersed feature about the T-lymphocytes, B-Lymphocytes, macrophages, langerhans cells, mast cells and eosinophils of peritumoral stroma were investigated in 82 cases with laryngeal carcinoma. A stepwise logistic regression analysis of eight clinicopathologic variables and the density of six kinds of tumor infiltrating cells in the study were analyzed with the clinical outcome of the patients. The results showed that T-lymphocytes was the major infiltrated cells. The other cells such as macrophages, langerhans cells, mast cells and eosinophils were also to be found in local infiltration, but the B-cell was scanty. All these cells except B-cell had significant effect on the 5-year survival rate of the patients. By the multivariate analysis, the peritumoral infiltrated eosinophils was the most influential variable affecting clinical outcome, followed by the peritumoral infiltrated T-lymphocytes and the tumor histologic grade. We concluded that tumor infiltrating cells played a critical role in local host antitumor immune reaction.

Adult↗

PubMed1996

[Clinical study on immunotherapy of ovarian cancer with tumor infiltrating lymphocytes].

OBJECTIVE: To investigate clinical usage of ovarian tumor infiltrating lymphocytes. METHODS: Tumor infiltrating lymphocytes (TIL) were isolated by cold digestion method, specimens being taken from: (1) infiltrating node on tumor surface. (2) the tumor proper. (3) the ovarian tissue. A randomized, double-blind study on two groups on ovarian cancer, totally 25 patients was conducted. The first group was given TIL and chemotherapy and the second group was given chemotherapy only. RESULT: The yields of infiltrating node on tumor surface were the highest (7.24 x 10(5)), in the tumor proper (2.49 x 10(5)), and in the ovarian tissue the lowest (2.07 x 10(5)). Growth of TIL in nodes on tumor surface increased 3,000 fold, in ovarian tissues and in tumor proper 2500 and 2000 times respectively. The most efficient killing activity was also presented in the infiltrating-nodes on tumor surface. CA125 decreased significantly, tumor regressed in two patients on follow-up by ultrasound, and ascites disappeared completely after one course of chemotherapy and TILs infusion. CONCLUSION: The yields of TIL in infiltrating nodes on tumor surface and their efficiency in killing activity were higher than those in tumor proper and ovarian tissues, and the infiltrating nodes on tumor surface were considered the best sites for obtaining specimens.

Adenocarcinoma↗

PubMed2025

Clinical Phenotype and Prognosis of Asymptomatic Patients With Transthyretin Cardiac Amyloid Infiltration.

IMPORTANCE: Patients with transthyretin (ATTR) cardiac amyloid infiltration are increasingly diagnosed at earlier disease stages with no heart failure (HF) symptoms and a wide range of cardiac amyloid infiltration. OBJECTIVE: To characterize the clinical phenotype and natural history of asymptomatic patients with ATTR cardiac amyloid infiltration. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data of all patients at 12 international centers for amyloidosis from January 1, 2008, through December 31, 2023. Inclusion criteria were asymptomatic ATTR cardiac amyloid infiltration, defined as an absence of HF history, HF signs and symptoms, diuretic therapy, and plasma cell dyscrasia with evidence of myocardial uptake on bone scintigraphy. If plasma cell dyscrasia was present, histologic confirmation of ATTR amyloid was required. EXPOSURE: Asymptomatic ATTR cardiac amyloid infiltration. MAIN OUTCOMES AND MEASURES: The primary outcomes were all-cause and cardiovascular (CV) mortality. The secondary outcomes were unplanned HF hospitalization, unplanned CV-related hospitalization, and a composite outcome of CV mortality and HF hospitalization. RESULTS: The study comprised 485 patients with asymptomatic ATTR cardiac amyloid infiltration (mean [SD] age, 74.9 [9.9] years, 85.8% male, 112 [23.1%] with hereditary ATTR amyloidosis), with 369 (76.1%) having grade 2 or 3 and 116 (23.9%) having grade 1 cardiac uptake at baseline. Patients with grade 2 or 3 uptake exhibited significantly more cardiac functional and structural abnormalities vs patients with grade 1 uptake. At 3 years, compared with grade 1 uptake, patients with grade 2 or 3 uptake had greater development of HF (54.3% [95% CI, 47.7%-61.3%] vs 23.1% [95% CI, 14.8%-35.1%]), greater outpatient diuretic initiation and N-terminal pro-B-type natriuretic peptide progression (35.0% [95% CI, 28.0%-43.2%] vs 12.4% [95% CI, 6.3%-23.7%]), and greater HF hospitalization (8.7% [95% CI, 5.9%-12.9%] vs 0%) and unplanned CV hospitalization (20.0% [95% CI, 15.7%-25.3%] vs 4.3% [95% CI, 1.6%-11.3%]). Over a median follow-up of 37 months (IQR, 20-64 months), the all-cause death rate was similar between patients with grade 1 vs 2 and 3 uptake; however, those with grade 2 or 3 compared with grade 1 uptake had a significantly higher risk of CV mortality (unadjusted hazard ratio, 5.30; 95% CI, 1.92-14.65). CONCLUSIONS AND RELEVANCE: This study shows that asymptomatic ATTR cardiac amyloid infiltration encompasses a wide spectrum of disease severity, with patients with grade 2 or 3 cardiac uptake experiencing an increased rate of CV events and CV mortality and patients with grade 1 uptake experiencing a lower CV event rate and predominantly non-CV mortality. These findings support the use of disease-modifying treatments in asymptomatic patients with grade 2 or 3 uptake and highlight the need of large-scale studies to assess their role in grade 1 uptake.

Humans↗

PubMed2001

Comparison of differentiated dendritic cell infiltration of autoimmune and osteoarthritis synovial tissue.

OBJECTIVE: Infiltration of rheumatoid arthritis (RA) synovial tissue (ST) by differentiated dendritic cells (DC) is a consistent feature in patients with active disease. However, mononuclear cells (MNC), including DC, may be nonspecifically chemoattracted to inflammatory sites regardless of etiology. Therefore, to evaluate the specificity of ST infiltration by differentiated DC, synovial biopsies from patients with RA, spondylarthropathy (SpA), osteoarthritis (OA), and gout were examined. METHODS: Formalin-fixed ST sections were analyzed by double immunohistochemical staining for vascularity and infiltration by differentiated DC, lymphocytes, and macrophages. RESULTS: DC containing nuclear RelB were found in perivascular MNC aggregates from patients with all arthritides studied. Infiltration by differentiated DC was similar in RA and SpA ST, but reduced in OA ST. Differentiated DC were always observed in close association with lymphocytes, and the correlation between these variables suggested that the infiltration of inflammatory sites by DC and lymphocytes was associated. CONCLUSION: Perivascular infiltration by DC, lymphocytes, and macrophages is nonspecifically related to inflammation, but signals present in RA and SpA ST lead to more intense cellular infiltration and accumulation.

Aged↗

PubMedDate not supplied

Infiltration of eosinophils in Hodgkin's disease involved lymph nodes predicts prognosis.

The number of infiltrating eosinophils were counted in tumour specimens from an unselected material of 140 cases of primary Hodgkin's disease (HD) and divided in three groups. Twenty-six cases (19 per cent) showed heavy infiltration (> 200 eosinophils/10 vision fields (VF)), 51 (36 per cent) moderate infiltration (11-200 eosinophils/10 VF and 63 virtually no infiltration (< 10 eosinophils/10 VF). The eosinophilic infiltration was significantly more pronounced in the nodular sclerosis subtype. Cases with heavy infiltration had a significantly worse disease-free survival compared to other cases. In a multivariate analysis, heavy eosinophilic infiltration was the most important factor for determining disease-free survival in all patients and also when patients above and below 60 were analysed separately.

Adolescent↗