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PubMedDate not supplied

Functional down-regulation of beta1 and beta2 integrins of lamina propria lymphocytes (LPL) and tumor-infiltrating lymphocytes (TIL) in colorectal cancer patients.

Integrins play an important role in various lymphocyte functions. In this study, we isolated lamina propria lymphocytes (LPL) and tumor-infiltrating lymphocytes (TIL) from normal and malignant tissues in patients with colorectal cancer, and examined the expression of beta1 and beta2 integrins on these lymphocytes quantitatively with two-color flow cytometry. Both LPL and TIL expressed a lower level of common beta1 chain (CD29) in CD4 and CD8 subpopulations than did peripheral blood lymphocytes (PBL). Among the associated alpha chains, the expression levels of alpha1 (CD49a) and alpha2 (CD49b) were slightly higher, whereas those of alpha4 (CD49d) and alpha6 (CD49f) were markedly reduced in LPL and TIL. No significant differences were observed in expressions of any alpha1 integrin chains between these two lymphocytes populations. Similarly, both alphaL (CD11a) and beta2 (CD18) were down-regulated in TIL and LPL with CD8+ cytotoxic phenotype, but not in those with CD4+ phenotype. CD8+ TIL expressed a slightly but significantly higher level of alphaLbeta2 than did CD8+ LPL. CD8+ LPL and CD8+ TIL consistently showed significantly decreased binding to purified ICAM-1, VCAM-1 and HT29 colon cancer cells as compared with CD8+ PBL. Although CD8+ TIL showed a slightly higher level of adhesion to these substrates than did CD8+ LPL, the level was much lower than that in PBL. The expression pattern and functional down-regulation of these integrins may be one of the reasons why TIL cannot eradicate the cancer cells in colorectal cancer.

Adenocarcinoma↗

PubMed2001

Comprehensive analysis of the frequency of recognition of melanoma-associated antigen (MAA) by CD8 melanoma infiltrating lymphocytes (TIL): implications for immunotherapy.

Fifty-nine tumor-infiltrating lymphocyte (TIL) cultures established from melanoma-invaded lymph nodes were screened for recognition of 28 melanoma-associated antigens (MAA) in association with31 HLA molecules. Twenty-three (39%) TIL lines reacted to at least one melanoma antigen. Melanosomal proteins were recognized by 19 TIL populations and the most prominent responses against these proteins were directed against Melan-A/MART-1 (mainly in association with HLA-A*0201) and gp100 (in association with diverse HLA contexts). Ten TIL populations reacted against 10 tumor-specific antigens, in association with 8 different HLA molecules. HLA-A*0201 and B*3501-restricted responses were the most frequent with, respectively, 17 and 7 responses directed against 5 distinct antigens. Unexpectedly, the recognition by TIL of different MAA was frequently restricted by a single HLA in individual tumors, and there was no evidence for the existence of dominant MAA epitopes between tumors,except for Melan-A/MART-1 antigen. This analysis also led to the detection of 21 new HLA-peptide complexes recognized by melanoma TIL. This study, which is to our knowledge the most comprehensive analysis of TIL specificity to tumor antigens, has several implications for the design of immunotherapeutic strategies based on immunization against selected tumor epitopes.

Animals↗

PubMed1989

Human tumor-infiltrating lymphocyte (TIL) cytotoxicity facilitated by anti-T-cell receptor antibody.

Long-term growth of tumor-infiltrating lymphocytes (TIL) in high concentrations of rIL-2 is required for generation of therapeutic numbers of cells for adoptive immunotherapy of human cancer. Under these conditions rIL-2 promotes both anti-tumor cytotoxicity and lymphocyte growth from tumors of several histological types. In a series of 16 consecutive tumors, studies of TIL-mediated cytotoxicity against different tumor targets were characterized by an initial strong tumor-non-specific cytotoxicity. With time, TIL bulk cultures became non-cytotoxic against all targets (median time = 38 days). Non-cytotoxic TIL bulk populations were capable of mediating strong cytotoxic responses if pre-treated with anti-T-cell antigen receptor antibody (TcR) before addition to targets. TIL populations were not, however, uniformly susceptible to anti-TcR-mediated cytotoxicity. Anti-TcR-mediated cytotoxicity was confined to CD8+ bulk populations (defined as populations with a CD4/CD8 ratio less than 1), with virtually no cytotoxicity observed in CD4+ populations (CD4/CD8 ratio greater than 2, (p less than 0.01). Both CD4 and CD8 populations expressed TcR antigen reactive with anti-TcR antibody. These results indicate that, despite poor in vitro anti-tumor cytotoxicity in short-term assays, CD8+ TIL are fully competent cytotoxic effector cells when subjected to strong activation signals via the TcR complex. In addition, these results imply that adoptively transferred CD4+ populations of TIL have in vivo biologic functions quite distinct from those of CD8+ populations and, further, that disparate clinical outcomes could reasonably be expected from the adoptive transfer of either population alone.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1990

In vivo administration of picibanil (OK-432) prior to tumor harvest leads to an enhancement of tumor-infiltrating lymphocyte (TIL) cytotoxicity.

TILs can be isolated and expanded in vitro in the presence of RIL-2. The resulting cells are highly cytotoxic in vitro and in vivo against a variety of tumor targets. Although most of the TILs bear T cell antigens on their cell surface, recent evidence suggests that natural killer (NK) cells may be part of the overall population of infiltrating cells. Based upon this evidence, we have evaluated the effects of Picibanil (OK-432), a well-known inducer of NK cell and T cell cytotoxicity, on TILs. OK-432 was administered intravenously at a dose of 100 micrograms, previously determined to be optimal for NK stimulation, to tumor-bearing animals. Two days later, control and experimental animals had their tumors harvested and processed in order to grow their TILs in vitro in complete medium containing RIL-2 at a final concentration of 1,000 U/ml. The following observations were made: 1) a greater than 300% increase in overall TIL number compared to controls on day 10 of culture returning to normal by day 30; 2) a marked increase in the percent of cells expressing cytotoxic and differentiation antigens in the experimental group compared to controls, such increase seen mostly from day 7 to day 10; 3) a marked increase in the cytotoxic activity of the experimental TILs against an NK-sensitive tumor target, the YAC-1 lymphoma, throughout the period of growth of the TILs (3-4 times controls) and to a lesser extent against an NK-resistant tumor target. These findings may have potential application, in immunotherapeutic trials against human tumors and may help to understand the reasons for the effectiveness of OK-432 in vivo against selected murine tumors.

Adenocarcinoma↗

PubMed1993

Autologous tumour-specific cytotoxic T-cell clone established from tumour-infiltrating lymphocytes (TIL) of malignant ascites in the absence of recombinant interleukin 2(rIL2): activation by autologous tumour cell alone.

Mixtures of tumour infiltrating lymphocytes (TIL) and tumour cells collected from malignant ascites of a patient with pancreatic cancer were cultured using a microplate without recombinant interleukin 2(rIL2). TIL rapidly proliferated from 21-51 days after the initiation of culture in 20 out of 30 wells tested. Cytotoxicity was examined in 5 out of the 20 TIL-growing wells. One CD8+ TIL (well-1) displayed autologous tumour-specific cytotoxicity. Repeated stimulation with autologous tumour cells, in the absence of rIL2, was required for further propagation in long-term (60 days) culture of TIL. Four clones were established from well-1 by limiting dilution without rIL2. Surface phenotypes of the 4 clones were the same as those of well-1, i.e., CD8+, CD16-, CD25+, HLA-DR+. And autologous tumour cells were required for continuous proliferation of these CD8+ T-cell clones. Both well-1 and the 4 clones displayed similar degrees of cytotoxicity restricted to autologous tumour cells. These results indicate that TIL from malignant ascites may contain precursor cytotoxic T-lymphocytes (CTL) sensitized in vivo to autologous tumour cells, and that TIL are able to grow for several weeks or more with substantial increases in cell numbers in the absence of rIL2.

Aged↗

PubMed2002

Therapeutic efficacy of melanoma-reactive TIL injected in stage III melanoma patients.

Adoptive therapy for cancer using tumor-infiltrating lymphocytes (TIL) has mainly been investigated in cancer patients with advanced stage disease. The limited clinical success has not been encouraging, although this might be explained by poor TIL specificity and/or high tumor burden. To re-evaluate the effectiveness of adoptive therapy, we analyzed the capacity of tumor-reactive TIL injection in preventing the further development of disease in stage III melanoma patients after complete tumor resection. A phase II/III randomized trial was performed on 88 melanoma patients, who received autologous TIL plus interleukin-2 (IL-2) or IL-2 only. The duration of relapse-free survival was analyzed, taking into account the immunological specificity of injected TIL and the number of metastatic lymph nodes removed before treatment. Kaplan-Meyer analysis revealed that the injection of tumor-reactive TIL was statistically correlated with prolonged relapse-free survival in patients with only one metastatic lymph node. Therefore, improved clinical outcome could be obtained after adoptive therapy by selecting appropriate groups of patients and monitoring the specificity of the injected TIL populations.

Adjuvants, Immunologic↗

PubMed2005

Evaluation of particulate filtering respirators using inward leakage (IL) or total inward leakage (TIL) testing--Korean experience.

Korean certification regulation for particulate filtering respirators requires inward leakage (IL) or total inward leakage (TIL) testing according to European Standard EN 13274-1, and the standard levels of compliance are similar to those of the European Standard. This study was conducted to evaluate particulate filtering respirators being commercially used in the Korean market using an IL or TIL test and the validity of standard level in Korea. Three half masks and 10 filtering facepieces (two top class, four 1st class and four 2nd class)-a total of 13 brand name respirators-were selected for the test with panels of 10 subjects. Each subject was classified with nine facial dimension grid squares in accordance with face length and lip length. IL or TIL testing was conducted at the laboratory of the 3M Innovation Center in which the experimental instruments and systems were established in compliance with European standards. The testing procedure followed EN 13274-1 (2001). As expected, leakages of half masks were less than those of filtering facepieces and the latter were significantly different among brands. TILs of the 1st class filtering facepieces were found to be much more than those of the 2nd class and the result may cause a wearer to get confused when selecting a mask. The main route leakage for filtering facepieces may not be the filter medium but the face seal. Therefore, it is necessary to develop well-fitting filtering facepieces for Koreans. Because leakages were significantly different for different facial dimensions, a defined test panel for IL or TIL testing according to country or race should be developed. A more precise method to demonstrate fit, for example, fit testing such as in the US regulations, will be needed before IL or TIL testing or when selecting a respirator. Another finding implies that geometric mean of five exercises for IL or TIL may be better than arithmetic mean to establish a standard individual subject mean.

Equipment Design↗

PubMed1990

[Study of cytotoxicity of recombinant interleukin-2 (rIL-2) expanded tumor infiltrating lymphocytes (TIL) in renal cell cancer].

We studied subsets and cytotoxicity of recombinant interleukin-2 (rIL-2) expanded tumor infiltrating lymphocytes (TIL) from renal cell cancer (RCC) patients. TIL were successfully expanded in 13 of 14 RCC cases using anti-CD3 during initial 48 hours of culture. Percentages of CD8 positive cells among rIL-2 expanded TIL at 1 tp 4 week(s) of culture were 56.2 +/- 15.1% (range 26.2 to 79.8%, N = 13) and not necessarily predominant over CD4 positive cells. NK and LAK activities of TIL at 3 to 6 weeks of culture were 31.6 +/- 15.8% (range 1.4 to 57.4%, N = 9) and 16.6 +/- 11.6% (range 3.8 to 35.6%, N = 6), respectively. Autologous and allogeneic RCC cytotoxicity of TIL at 3 to 4 weeks of culture were 17.9 +/- 19.7% (range 0 to 47.6%, N = 4) and 18.9 +/- 14.8% (range 0 to 47.3%, N = 12), respectively. Since there was no statistical difference between them, autologous specific cytotoxicity was not demonstrated. From these results of present study, it is unlikely that most of effector cells of rIL-2 expanded TIL in autologous RCC lysis are major histocompatibility complex restricted cytotoxic T cells. And we concluded that it is doubtful that TIL is significantly superior over LAK cells in immunotherapy of human RCC.

Carcinoma, Renal Cell↗

PubMed1999

[In vitro hepatic targeting tendency of galactosyl-anti CD3 McAb-TILS].

This study was undertaken to enhance the hepatic targeting tendency of tumor infiltrating lymphocytes (TILs) and hence to lower the recurrence rate of primary liver cancer after hepatectomy. Galactosyl-anti CD3McAb-TILs were prepared and then were incubated together with hepatocytes. Their interaction through asialoglycoprotein receptor-mediated mechanism was observed under the inverted phase contrast microscope. The carbohydrate density of galactosyl-anti CD3McAb and the combining rate of galactosyl-anti CD3McAb with TILs were measured. The results revealed that galactosyl-anti CD3 McAb-TIL obviously were adhered to hepatocytes. The carbohydrate density of galactosyl-anti CD3McAb was 62.18, and the combining rate of galactosyl-anti CD3McAb with TILs was 97.9%. The results suggested that in vitro hepatic targeting tendency of galactosyl-anti CD3McAb-TILs was satisfactory, and that the carbohydrate density of 62.18 and the combining rate of 97.9% ensured the effective use of TILs.

Animals↗

PubMed2004

[Experimental study on the activity of Staphyloccocal enterotoxin A liposome for inducing cytotoxicity of TIL from human hepatocellular carcinoma against tumor cells].

OBJECTIVE: To investigate the activity of Staphyloccocal enterotoxin A liposome (L-SEA) for inducing cytotoxicity of tumor infiltrating lymphocytes (TIL) against tumor cells. METHODS: TIL were isolated from the tumor tissues of five hepatocellular carcinoma patients. L-SEA, SEA and IL-2 were tested in vitro for their activity levels in stimulating TIL proliferation. The TNF-alpha and IFN-gamma secretion and cytotoxicity of TIL against HepG-2 liver cancer cells were estimated by ELISA and MTT, respectively. RESULTS: Both L-SEA and SEA significantly stimulated the proliferation of TIL. The cytokine secretion of L-SEA group was significantly higher than that of IL-2 group (P < 0.05). There was no significantly statistical difference in cytokine secretion between L-SEA group and SEA group (P > 0.05) except that IFN-gamma secretion of L-SEA group was lower than that of SEA group at day 4 (P < 0.05). Both L-SEA and SEA had potent ability to induce TIL cytotoxicity against HepG-2 cells. And no significant difference was observed between these two groups (P > 0.05). CONCLUSION: These results suggest that L-SEA is as efficient as SEA in activating TIL.

Adult↗

PubMed1984

[Tumor-specific cytotoxicity of tumor infiltrating lymphocytes (TIL) induced with TCGF in murine mammary carcinoma].

A medullary carcinoma with lymphocytic infiltration is associated with relatively good prognosis following radical mastectomy in breast cancer. This suggests that tumor infiltrating lymphocytes (TIL) play an important role in the immunological resistance of the host against cancer. The cytotoxic activities of TIL in murine mammary carcinoma SC42 and SC115 of syngeneic DS mice were assessed with 51Cr release assay in this study. The tumor masses were minced and trypsinized, and lymphoid cell rich fraction was separated with Percoll discontinuous gradient centrifugation. During 10 days culture with T cell growth factor (TCGF) obtained from Con A stimulated rat spleen cells, the tumor cells were collapsed and lymphocytes were expanded. The cultured TIL from SC42 tumor had stronger cytotoxicity against SC42 tumor cells than the cultured TIL from SC115 tumor and the cultured spleen cells of SC42 tumor bearer, and the cultured TIL from SC115 tumor showed predominant activity against SC115 tumor cells. Nonspecific cytotoxic activity and natural killer (NK) activity of these TIL were weaker than the cultured spleen cells. The culture of the spleen cells with the tumor cells and TCGF failed to induce tumor-specific cytotoxic lymphocytes. Moreover, the tumor-specific cytotoxicity was reduced by the treatment of anti thy-1, 2 and complement, and NK activity was reduced by the treatment of anti-asialo GM1 and complement. These results indicate that the tumor-specific cytotoxicity is latent in the T cell population of TIL and is induced by the culture with TCGF.

Animals↗

PubMed2025

T cell subsets of urine-derived lymphocytes (UDLs) serve as an indicator of TILs and reflect immunological sex differences in bladder cancer.

BACKGROUND: Bladder cancer is unique among visceral malignancies in that urine, which can be easily obtained, has prolonged contact with bladder tumors. Urinary biomarkers offer the potential to provide insight into the host and tumor immune microenvironment to guide therapeutic strategies. We evaluated the immune cellular composition of urine (urine-derived lymphocytes (UDLs)) versus tumor (tumor-infiltrating lymphocytes (TILs)). METHODS: We employed high-dimensional flow cytometry analyses on immune cells from tumors (TILs), urine (UDLs), and peripheral blood (peripheral blood mononuclear cells) among patients with bladder cancer. We performed multiplexed immunofluorescence (mIF) of matched tumors to provide spatial context to our findings, comparing deep/invasive and superficial/urine-facing regions of matched tumors. RESULTS: Our findings suggest that the CD4+ and CD8+ T cell subsets of UDLs characterized by flow cytometry had similar phenotypic profiles to those found in TILs (cell clusters quantified by multidimensional scaling and differentiation states). Results of mIF imaging with a panel of phenotypic and functional T cell markers suggested that UDLs reflected TILs in both superficial and deep tumor sections. We also found sex-dependent patterns in TILs and UDLs, indicating the male bladder cancer tumor microenvironment is enriched in exhausted CD4+ and CD8+ T cells, while the female bladder cancer microenvironment is enriched for activated T cells. CONCLUSIONS: Assessment of UDLs opens avenues of non-invasive biomarker development in clinical settings where bladder cancer TILs are hypothesized to predict clinical response. UDLs may also reflect sex-based differences in antitumor immunity.

Humans↗

PubMed1997

Prognostic value of tumour-infiltrating lymphocytes (TILs) in colorectal cancer.

Clinical follow-up data of 276 colorectal adenocarcinoma patients treated in Kuopio University Hospital between 1976 and 1986 and followed up for a mean of 14 years were analysed. The clinical findings were correlated with tumour-infiltrating lymphocytes (TILs) and with histological and quantitative factors including nuclear parameters and volume-corrected mitotic index. In univariate survival analysis, TNM classification, Dukes' stage, histological grade, and TILs were significant predictors of survival. TNM classification, Dukes' stage, and TILs also predicted recurrence-free survival. In multivariate analysis, TILs were an independent prognostic factor of survival in all cases, as well as in patients with T1-4N0-3M0 and T1-4N1-3M1. TILs also independently predicted recurrence-free survival. TILs can provide important prognostic information in colorectal cancer to be used in evaluating for adjuvant therapy in different tumour stages.

Adenocarcinoma↗

PubMed1997

Immunosensitization of prostate carcinoma cell lines for lymphocytes (CTL, TIL, LAK)-mediated apoptosis via the Fas-Fas-ligand pathway of cytotoxicity.

Several reports suggest that immunotherapy mediated by cytotoxic lymphocytes is beneficial in the destruction of drug-resistant tumor cells. Cytotoxic T lymphocytes kill target cells by two main mechanisms, namely by the perforin pathway and by the Fas-ligand (Fas-L) pathway. The role of the Fas-L pathway in tumor cell killing is not clear because many Fas(+)-expressing tumor cells are resistant to the Fas-L agonist cytotoxic anti-Fas antibody. The human prostate tumor cell lines (PC-3, DU145, and LnCAP) express Fas on the cell surface but are resistant to killing by anti-Fas antibody. This study examined the sensitivity of prostate tumor cells to Fas-L-mediated cytotoxicity and sensitization of the tumor cells by drugs to Fas-L-mediated killing. All three prostate tumor cell lines are resistant to Fas-L killing as determined by the use of the murine CTL hybridoma PMMI that kills only through the Fas-L pathway. However, the addition of subtoxic concentrations of CDDP or VP-16 significantly sensitized the PC-3 and DU145, but not LnCAP, tumor cells to Fas-L killing and apoptosis by PMMI. The sensitization of tumor cells by drugs was inhibited by neutralizing anti-Fas antibody. These findings demonstrate that immunoresistant Fas(+)-expressing DU145 and PC-3 prostate tumor cells can be sensitized by drugs to Fas-L killing. We then examined the role of Fas-L killing by TIL and LAK cells. All three prostate tumor cell lines were sensitive to killing by TIL and LAK and cell killing was primarily mediated through the Ca(2+)-dependent perforin pathway because it was blocked by the addition of EGTA/MgCl2. Sensitization by CDDP or VP-16 did not significantly augment killing of untreated tumor cells by TIL or LAK cells. However, in the presence of EGTA/MgCl2, the addition of CDDP or VP-16 significantly augmented killing of PC-3 and DU145, but not LnCAP, by TIL and LAK, and killing was blocked by neutralizing anti-Fas antibody. These findings demonstrate that both TIL and LAK exhibit a Fas-L-mediated killing pathway that is revealed once the perforin pathway is blocked by the Ca2+ chelator EGTA/MgCl2. Altogether, these findings show that drug-resistant, Fas(+)-expressing PC-3 and DU145 prostate tumor cells can be sensitized by CDDP and VP-16 to killing by Fas-L-bearing CTL, TIL, and LAK cells. Sensitization of tumor cells by drugs may augment the efficacy of immunotherapy in the eradication of tumor cells that are resistant to Fas-L-mediated killing.

Animals↗

PubMed1997

[Dynamic distribution in vivo of TIL from human tongue cancer after local injection in animal model].

On the basis of established nude mice transplanted tumor model of human tongue squamous cell carcinoma, peritumor injection was performed with 3H-TdR labeled TIL from human tongue cancer after 4 weeks culture. The dynamic distribution of 3H-TIL in vivo was learned through detecting the radioactivity of the target tissues. The results demonstrated that 3H-TIL was found in the whole body. There were about 2.1-30 times more in tumor tissues than in normal tissues and 3H-TILs even collected in the tumor tissues distal to the injective sites. The nearer to the injective sites the tumor tissues, the more 3H-TIL collected. It showed that local injection of TIL could be expected to exert a better antitumor effect.

Adult↗

PubMed1990

Tumor infiltrating leukocytes (tils) during progressive tumor growth and BCG-mediated tumor regression.

Tumor regression was induced by intralesional injection with BCG, 7 days after inoculation of line 10 hepatocellular carcinoma cells into strain 2 guinea pigs. Tumor-infiltrating leukocytes (TILS) were characterized immunohistochemically with 11 monoclonal antibodies (MoAbs) during the induction phase of line 10-immunity, and during immune-mediated regression of the tumor, at days 12 and 28 after tumor cell inoculation, respectively. At day 5 after BCG-injection (day 12 after tumor cell inoculation), there were no major differences between the TIL subpopulations of the BCG-treated and untreated tumors. The TILS were mainly T-cells, as identified by MoAbs against Pan T-cells (CT5), T-cytotoxic/suppressor cells (CT6) and T-helper/inducer cells (H155). A limited number of macrophages was also present. However, at day 21 after BCG-treatment (28 days after tumor cell inoculation), the fibrous stroma was increased dramatically in most of the BCG-treated tumors, and as a result, the tumor cell islets were smaller than in control tumors. In the BCG treated tumors, the numbers of T-cells and macrophages were increased. In growing and regressing tumors, MHC class I and II antigens were strongly expressed in TILS and in the tumor stroma. Line 10 tumor cells prior to inoculation expressed no MHC class I or II antigens. In the centers of the tumor islets at days 12 and 28, expression of these antigens was not found. However, MHC class I and II antigens were expressed on tumor cells at sites where they lay close to the fibrous stroma or TILS. This observation was made in progressively growing tumors and was most apparent in BCG-treated tumors.

Animals↗

PubMed2005

Characterization of IL-2-activated TILs and their use in intrapericardial immunotherapy in malignant pericardial effusion.

Pericardial effusion (PE) and cardiac tamponade caused by malignant pericarditis are critical conditions in cancer patients, which still lack a recommended protocol for their long-term management. Percutaneous pericardiocentesis and simple drainage are commonly performed as the initial treatment. The aims of this study were to investigate the presence of cytotoxic T lymphocytes (CTLs) in malignant PE and to determine the clinical response to administering autologous tumor-infiltrating lymphocytes (TILs) into the pericardial cavity. Initially, we identified human lymphocyte antigen class-I-restricted and tumor-specific CTLs within the interleukin-2 (IL-2)-activated TILs in PEs from four patients, on the basis of interferon-gamma production and lactate dehydrogenase-release assays. Clinically we observed favorable responses to the pericardial transfer of IL-2-activated autologous TILs in four patients: one male with advanced esophageal cancer, one female with recurrent lung cancer and two females with recurrent breast cancer, respectively. Autologous TILs from PEs were expanded in vitro with IL-2, characterized for CD3, CD4 and CD8 markers, checked for contamination and then infused into the patient's pericardial space through a catheter. This was repeated biweekly. After treatment, there were no signs of recurrence of PE in either case, as determined by radiography, echocardiography and computed tomography. The only adverse effects seen were grade 1 fevers. These results suggested that intrapericardial cellular immunotherapy with autologous TILs could be a safe and effective treatment for controlling malignant pericarditis with associated cardiac tamponade, and that tumor-specific CTLs present in malignant PE might be important for tumor rejection.

Aged↗

PubMed2000

Expression of costimulatory molecules CD80 and CD86 and their receptors CD28, CTLA-4 on malignant ascites CD3+ tumour-infiltrating lymphocytes (TIL) from patients with ovarian and other types of peritoneal carcinomatosis.

Costimulation of T lymphocytes by the leucocyte surface molecules CD80 and CD86 expressed on antigen-presenting cells (APC) is required for the development of T cell responses. The CD28 and CTLA-4 molecules on T cells serve as receptors for the CD80 and CD86 costimulatory antigens. We have examined the frequency of expression of CD80 (B7.1), CD86 (B7.2), CD28 and CTLA-4 surface antigens on TIL isolated from malignant ascites or peritoneal washings of 26 patients with ovarian carcinoma and five patients with non-ovarian peritoneal carcinomatosis. Expression of CD80 and CD86 antigen was detected by reverse transcription-polymerase chain reaction (RT-PCR), and by FACS analysis. Significantly higher proportions of intraperitoneal CD3+ cells expressed CD86 antigen than the CD80 antigen (14 +/- 9% versus 3 +/- 3%, P < 0.05). Moreover, CD3+CD86+ cells were significantly more frequent in the peritoneal fluid (14 +/- 9%) than in the peripheral blood (3 +/- 0.4%, P < 0.05) of ovarian patients or normal controls (3 +/- 1%). CTLA-4 and CD28 antigen were expressed, respectively, on 9 +/- 4% and 86 +/- 14% of ascitic CD3+ cells of ovarian cancer patients. Both CD80 and CD86 antigens were expressed primarily on HLA-DR+ ascites TIL and were present in a very low proportion of HLA-DR- ascites TIL. These HLA-DR+ cells may represent a population of lymphocytes that have been activated in vivo, and function as APC. An anti-CD86 MoAb or a combination of anti-CD86 and anti-CD80 MoAbs significantly inhibited the proliferation of cultured intraperitoneal TIL. We have shown that in addition to CD28 and CTLA-4, CD3+ intraperitoneal TIL express the costimulatory molecules CD80 and CD86. The expression of these molecules on T cells could be dependent upon certain factors in the tumour microenvironment that could determine the outcome of in vivo immune responses.

Abatacept↗