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At least 19 recordsLinked to original sources
PubMed2026

Associations of TILs and genomic alterations in HER2+ early breast cancer.

This study investigated the associations between tumor-infiltrating lymphocytes (TILs), genomic features, and prognosis in HER2+ early breast cancer (EBC) patients receiving adjuvant trastuzumab. We retrospectively analyzed 864 HER2+ EBC patients from Shanghai Ruijin Hospital (2009-2017). The optimal threshold of TILs for predicting disease-free survival (DFS) and overall survival (OS) was explored. Whole-exome sequencing (WES) on 261 tumors assessed the mutational profiles, tumor mutational burden (TMB), and copy number alteration (CNA). Associations between these genomic features, TIL levels, and prognosis were further evaluated. TILs showed a right-skewed distribution (median: 15%, IQR: 1-30%), and higher TIL levels were significantly associated with hormone receptor negativity and high histologic grade (P < 0.001). A 15% TIL threshold optimally predicted prognosis, with low-TIL (&#x2264;15%, 63.0%) patients showing inferior DFS (HR: 1.63, P = 0.009) and OS (HR: 2.12, P = 0.037). WES identified frequent mutations in TP53 (62.8%), PIK3CA (34.5%), and BRCA2 (9.6%). A higher TIL density was observed in TP53-wild-type, low-TMB or low-CNA tumors (P < 0.05). PIK3CA mutations conferred a significant DFS advantage. Integrating TIL level with PIK3CA or BRCA2 mutational status yielded distinct DFS trajectories (log-rank P = 0.023 and 0.040, respectively); patients with both high TIL levels and either PIK3CA or BRCA2 mutations had the most favorable outcomes. Stromal TILs at a 15% cutoff provide robust prognostic information in trastuzumab-treated HER2+ EBC. Integrating TIL levels with PIK3CA or BRCA2 mutational status enables refined risk stratification, offering a practical framework for personalized treatment decisions.

Humans↗
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↗
PubMed1992

[The antitumor effects of tumor-infiltrating lymphocytes (TIL) being proliferated in vitro].

Tumor-infiltrating lymphocytes (TIL) were isolated from 19 solid tumors by means of in vitro digestion and discontinuous density gradient centrifugation. The average amount of TIL harvested from one gram of tumor tissue was 1.3 x 10(6). A four-week long term cultivation procedure was performed in 8 of the 19 specimens with rIL-2, and the number of TIL had then been expanded for 30 to 150 times more. Phenotypic analysis showed that most of TILs obtained were OKT3+ lymphocytes, and the ratio of OKT4+ and OKT8+ was decreased coincidently during the cultivation in vitro. The experiment showed that TILs exhibited stronger anti-autologous tumor effects than that to the allogeneic tumors through both in vitro and in vivo studies.

Animals↗
PubMed1991

[Adoptive immunotherapy and metastasized cancer of the kidney. Regulator effects of interleukin-4 on tumor infiltrating lymphocytes (TIL)].

Adoptive immunotherapy is a new therapeutic approach of the treatment of advanced renal cell cancer. Experimental studies have shown that the cells with the highest cytolytic activity are tumor infiltrating lymphocytes (TIL). The effects of interleukin-4 (IL-4) on the expansion, proliferation, phenotype and antitumor activity of TIL were studied. Cultures were obtained from three primary renal tumors and one group of tumor invaded, regional lymph nodes. IL-4 induced a significant increase in lymphocytes expansion and proliferation, but the response was dependent of the concurrent dose of IL-2 in culture. TIL grown in the presence of IL-4 significantly reduced the level of non specific, non MHC restricted antitumor activity while exhibiting no effect on the level of autologous killing. The effects of irradiated autologous tumor stimulation on TIL cultures were also evaluated. Addition of autologous tumor increased expansion and proliferation of all cultures and significantly enhanced levels of autologous killing. IL-4 and autologous tumor stimulation are effective growth factors when used in combination with a lose dose IL-2 regimen and may be of significant benefit in the expansion of TIL for clinical trials.

Adenocarcinoma↗
PubMed1992

[Observation on the phenotypic changes of tumor-infiltrating lymphocytes(TIL) during cultivation in vitro].

Tumor-infiltrating lymphocytes (TIL) were isolated from 5 malignant tumors and their phenotypes were analyzed by flow cytometry when co-cultured with recombinant human interleukin-2 (rIL-2). It was shown that 84% (+/- 8%) of TILs were OKT3+in phenotype after three weeks of cultivation. Among these, OKT8+subpopulations amounted to 77%(+/- 13%), while OKT4+subpopulations were only 14%(+/- 11), and the ratio of OKT4+/OKT8+changed from 0.5:1 (in the first week) to 0.18 (in the third week). Two parameters (mode and peak) in the histogram of flow cytometry varied in accordance with the variations of TIL's phenotypes. The results suggested that TILs stimulated by rIL-2 could be enriched predominantly in a single subpopulation (OKT8+), which might be related with their specific effects against tumor growth.

CD4-CD8 Ratio↗
PubMed1991

Paired tumour infiltrating lymphocyte (TIL) and tumour cell line from bladder cancer: a new approach to study tumour immunology in vitro.

This paper reports the first example of tumour infiltrating lymphocytes (TILs) and a tumour cell line from the same individual and analyses their characteristics. The tumour cell line (CAT), derived from a patient with well-differentiated (G3pTa) TCC, has been in culture for 24 months and subcultured more than 100 times. Epithelial origin was established by electronmicroscopy and use of a range of monoclonal antibodies (Mabs) against cytokeratins. The TILs isolated from the same tumour expressed all the phenotypic characteristics of normal activated T cells and demonstrated low levels of cytotoxicity against the autologous tumour line (CAT). Comparison of cell surface molecules of these cells revealed the loss of HLA-B7, B44 and Bw6 from the CAT cells whilst maintaining HLA-A2, A3 and Bw4. Karyotypic analysis demonstrated three rearranged chromosomes (between chromosomes 4 and 11, 10 and 13, 11 and 17) on CAT cells. The potential that study of paired autologous tumour cells and TILs in culture offers for studying the role of MHC antigens in tumour rejection and the impact of different approaches to correcting the defect are reviewed.

Antibodies, Monoclonal↗
PubMed1992

Gamma-interferon enhances the cytotoxic activity of interleukin-2-induced peripheral blood lymphocyte (LAK) cells, tumor infiltrating lymphocytes (TIL), and effusion associated lymphocytes.

The effect of gamma-interferon (IFN-gamma) on the induction of interleukin-2 (IL-2) activated killer cell activity was studied: (I) in peripheral blood lymphocytes (LAK cells) from cancer patients and healthy donors, (II) in lymphocytes infiltrating solid tumors (TIL) from melanoma and breast cancer patients, and (III) in pleural effusion associated lymphocytes (EAL) from patients with lung adenocarcinoma. The coculture of LAK, TIL and pleural effusion mononuclear cells (MNC) with several doses of IFN-gamma (10, 50, 250, and 1250 U/ml) and a low dose of IL-2 (10 U/ml) for 5 days resulted in a synergistic effect on the cytotoxicity of these cells against several tumor cell lines. Furthermore there was a potentiation in the proliferation of MNC after a 5-day culture. The induction of lymphocyte cytotoxicity by a combination of IFN-gamma with low doses of IL-2 may be helpful in designing more effective cancer immunotherapeutic protocols with LAK, TIL or EAL.

Cytotoxicity, Immunologic↗
PubMed1992

[An experimental study of the antitumor activity of tumor-infiltrating lymphocytes (TIL) in human tongue carcinoma in vitro].

In the present paper tumor-infiltrating lymphocytes (TIL) from lymph nodes of human tongue carcinoma patients were obtained by discontinuous density gradients centrifugation and used in experimental treatment. The results showed that 1.3 x 10(8) TIL/g lymph node tissue were gotten by the above method. TIL activated by rIL-2 exhibited higher cytotoxicity to Tca8113 cell line than the same patient's LAK cells (81.48% and 24.69% respectively). There was significantly difference in the cytotoxicity between two groups (P < 0.01), indicating that TIL were the best source of adoptive immunotherapy.

Adult↗
PubMed1990

[Receptor-mediated cancer therapy--tumoricidal cytokines, adoptive therapy of LAK, TIL].

Three modes of receptor-mediated cancer therapy were reviewed presenting our own data. Employment of tumoricidal cytokines (IFN, TNF, LT) to this type of therapy has been expected to be the most promising approach. However, preclinical and clinical results so far obtained, revealed that they were useful only for the very limited diseases including renal cancer or some hematological malignancies. Second approach is to utilize growth factors conjugated with toxin or carzinostatin which are readily internalized into tumor cells. In this context, transferrin-neocarzinostatin was examined in our laboratory both in vitro and in vivo for its anticancer activity and was found to suppress tumor growth more significantly than neocarzinostatin alone on the basis of molar ratio. Thus this approach may be worthy to be clinically investigated. Adoptive therapy of lymphokine activated killer (LAK) or tumor infiltrating lymphocyte (TIL) may also be categorized into receptor mediated cancer treatment since both are activated by signals through IL-2 receptor. Although clinical evaluation is still on going, the therapy appears to be effective only when effector cells are administered locally to tumors.

Humans↗
PubMed1992

Flavone acetic acid (FAA) with recombinant interleukin-2 (TIL-2) in advanced malignant melanoma. II: Induction of nitric oxide production.

Plasma samples were collected from 20 patients undergoing phase I clinical trial with flavone-8-acetic acid (FAA; 4.8 g m-2 per dose) in combination with recombinant human interleukin-2 (rhIL-2; 6-18 i.u. m-2 per day) for the treatment of metastatic melanoma. Samples were analysed for nitrate content as an indication of the oxidation of L-arginine to nitric oxide. Pretreatment plasma nitrate levels (53 +/- 4 microM) were significantly above those of healthy volunteers (19 +/- 4 microM). The maximum plasma nitrate concentration obtained after treatment, 190 +/- 29 microM (range 49 to 655 microM), was comparable to that of mice treated with FAA. Most of the increases occurred 3-5 days after initiation of a 5 day infusion of rhIL-2, but three of the increases occurred within 2 days of a 1 h infusion of FAA alone. The maximum plasma nitrate concentrations of the three patients which underwent remission (two complete, one partial) following treatment (368 +/- 143 microM) were significantly higher (P < 0.05) than those of patients with progressive disease. Hypotension was the major dose-limiting side effect, and there was no relationship between the degree of hypotension and the rise in plasma nitrate. The results provide evidence that treatment of patients with FAA and rhIL-2 induce the synthesis of nitric oxide, a physiological mediator and potential cytotoxic agent.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

'Til death do us part: intimacy and sexuality in the marriages of Alzheimer's patients.

1. Alzheimer's disease (AD) is likely to have a significant effect on sexual behavior, but both patient and partner will still have sexual feelings and needs. 2. Research has shown that a high proportion of men with AD develop erection problems, but causes of their erection difficulties are not understood. 3. Research has shown that inappropriate sexual behavior in AD patients is uncommon, although it can be very troubling to the family and health-care provider if it occurs. 4. More professionals need to be trained to discuss sexual issues openly and sensitively with AD patients and partners and to offer useful clinical suggestions.

Adaptation, Psychological↗
PubMed1975

[Epidemiology of Tuberculosis in Children from 1968 til 1973 in Schleswig-Holstein (author's transl)].

In Schleswig-Holstein 271 children (131 boys, 140 girls) were treated for tuberculosis between january 1968 and June 1973; 84% were aged 5--14 years, 14% between 1--4 years and 29% between 0--1 year. Each year, nearly the same number of infections occurred in the various districts of the country. In 246 children a primary form of tuberculosis was diagnosed (in 11 cases with pleurisy). 11 patients tuberculous meningitis, 3 patients miliary tuberculosis and 5 patients another form of the disease, 18 of 271 patients (7%) had been vaccinated against tuberculosis as newborns; in 4 of these children tubercle bacilli could be isolated. BCG vaccination had been done 8--12 years before disease in 11 cases and 1--5 years before disease in 7 cases. None of these vaccinated children had a hematogenous tuberculosis or died. Of the non-vaccinated children two patients had meninogencephalitis and died. The other children were cured by chemotherapy, 12 children by additional surgery. The morbidity of tuberculosis in Schleswig-Holstein was 7--10 per 100000 children. Therefore, further BCG vaccination, chemoprophylaxis or preventive chemotherapy seems necessary. Early recognition of tuberculosis in old persons may be of practical value to prevent infections in children.

Adolescent↗