Non-cancerous liver infiltrating lymphocytes of hepatitis C and tumor-infiltrating lymphocytes
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ORGANISM(S): Homo sapiens
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PROVIDER: S-DIXA-D-1003 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:Study goal is to disclose features of gene expressio profile of non-cancerous liver-infiltrating lymphocytes of type C hepatitis patients with hepatocellular carcinomas and tumor-infiltrating lymphocytes of type C hepatitis patients with hepatocellular carcinomas. Keywords: gene expression profile, non-cancerous liver-infiltrating lymphocytes, tumor-infiltrating lymphocytes, type C hepatitis, hepatocellular carcinoma Non-cancerous liver-infiltrating lymphocytes were obtained by laser capture microdissection from surgically resected liver tissues of 12 type C hepatitis patients with hepatocellular carcinoma. The mRNA was amplified and expression profile was comprehensively analyzed with reference RNA using oligo-DNA chip. Tumor-infiltrating lymphocytes were obtained by laser capture microdissection from surgically resected cancer tissues of 12 type C hepatitis patients with hepatocellular carcinoma. The mRNA was amplified and expression profile was comprehensively analyzed with reference RNA using oligo-DNA chip.
2010-06-25 | E-GEOD-10461 | biostudies-arrayexpress
Project description:Study goal is to disclose features of gene expressio profile of non-cancerous liver-infiltrating lymphocytes of type C hepatitis patients with hepatocellular carcinomas and tumor-infiltrating lymphocytes of type C hepatitis patients with hepatocellular carcinomas. Keywords: gene expression profile, non-cancerous liver-infiltrating lymphocytes, tumor-infiltrating lymphocytes, type C hepatitis, hepatocellular carcinoma
2008-02-13 | GSE10461 | GEO
Project description:Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) is arguably the most effective treatment for patients with metastatic melanoma. With higher response rates than ipilimumab or IL-2, and longer durations of response than vemurafenib, TIL therapy carries the potential to transform current outcomes in melanoma, while also defining the way cell-based immunotherapy gets incorporated into mainstream cancer treatment. This paper will review the current state of TIL therapy in melanoma, the strategies to improve its efficacy, the current obstacles, and future directions to expand the availability of TIL to the general patient population.
| S-EPMC3462483 | biostudies-literature
Project description:Liver is the third most common organ for breast cancer (BC) metastasis. Two main histopathological growth patterns (HGP) exist in liver metastases (LM): desmoplastic and replacement. Although a reduced immunotherapy efficacy is reported in patients with LM, tumor-infiltrating lymphocytes (TIL) have not yet been investigated in BCLM. Here, we evaluate the distribution of the HGP and TIL in BCLM, and their association with clinicopathological variables and survival. We collect samples from surgically resected BCLM (n = 133 patients, 568 H&E sections) and post-mortem derived BCLM (n = 23 patients, 97 H&E sections). HGP is assessed as the proportion of tumor liver interface and categorized as pure-replacement ('pure r-HGP') or any-desmoplastic ('any d-HGP'). We score the TIL according to LM-specific guidelines. Associations with progression-free (PFS) and overall survival (OS) are assessed using Cox regressions. We observe a higher prevalence of 'any d-HGP' (56%) in the surgical samples and a higher prevalence of 'pure r-HGP' (83%) in the post-mortem samples. In the surgical cohort, no evidence of the association between HGP and clinicopathological characteristics is observed except with the laterality of the primary tumor (p value = 0.049) and the systemic preoperative treatment before liver surgery (p value = .039). TIL is less prevalent in 'pure r-HGP' as compared to 'any d-HGP' (p value = 0.001). 'Pure r-HGP' predicts worse PFS (HR: 2.65; CI: (1.45-4.82); p value = 0.001) and OS (HR: 3.10; CI: (1.29-7.46); p value = 0.011) in the multivariable analyses. To conclude, we demonstrate that BCLM with a 'pure r-HGP' is associated with less TIL and with the worse outcome when compared with BCLM with 'any d-HGP'. These findings suggest that HGP could be considered to refine treatment approaches.
| S-EPMC10724185 | biostudies-literature
Project description:The accumulation of tumor infiltrating lymphocytes (TILs) in ovarian cancer is prognostic for increased survival while increases in immunosuppressive regulatory T-cells (Tregs) are associated with poor outcomes. Approaches that bolster tumor-reactive TILs may limit tumor progression. However, identifying tumor-reactive TILs in ovarian cancer has been challenging, though adoptive TIL therapy in patients has been encouraging. Other forms of TIL immunomodulation remain under investigation including Treg depletion, antibody-based checkpoint modification, activation and amplification using dendritic cells, antigen presenting cells or IL-2 cytokine culture, adjuvant cytokine injections, and gene-engineered T-cells. Many approaches to TIL manipulation inhibit ovarian cancer progression in preclinical or clinical studies as monotherapy. Here, we review the impact of TILs in ovarian cancer and attempts to mobilize TILs to halt tumor progression. We conclude that effective TIL therapy for ovarian cancer is at the brink of translation and optimal TIL activity may require combined methodologies to deliver clinically-relevant treatment.
| S-EPMC4622931 | biostudies-literature
Project description:The immune system plays a pivotal role in tumor establishment. However, the role of T-lymphocytes within the tumor microenvironment as major cellular component of the adaptive effector immune response and their counterpart, regulatory T-cells (Treg), responsible for suppressive immune modulation, is not completely understood. This is partly due to the lack of reliable technical solutions for specific cell quantification in solid tissues. Previous reports indicated that epigenetic marks of immune cells, such as the Treg specifically demethylated region (TSDR) within the FOXP3 gene, may be exploited as robust analytical tool for Treg-quantification. Here, we expand the concept of epigenetic immunophenotyping to overall T-lymphocytes (oTL). This tool allows cell quantification with at least equivalent precision to FACS and is adoptable for analysis of blood and solid tissues. Based on this method, we analyse the frequency of Treg, oTL and their ratio in independent cohorts of healthy and tumorous ovarian, colorectal and bronchial tissues with 616 partly donor-matched samples. We find a shift of the median ratio of Treg-to-oTL from 3-8% in healthy tissue to 18-25% in all tumor entities. Epigenetically determined oTL frequencies correlate with the outcome of colorectal and ovarian cancers. Together, our data show that the composition of immune cells in tumor microenvironments can be quantitatively assessed by epigenetic measurements. This composition is disturbed in solid tumors, indicating a fundamental mechanism of tumor immune evasion. Epigenetic quantification of T-lymphocytes serves as independent clinical parameter for outcome prognosis.
| S-EPMC3278789 | biostudies-other
Project description:Infiltrating T lymphocytes are frequently found in malignant tumors and are suggestive of a host cancer immune response. Multiple independent studies have documented that the presence and quantity of tumor-infiltrating lymphocytes (TILs) are strongly correlated with increased survival. However, because of methodological factors, the exact effect of TILs on prognosis has remained enigmatic, and inclusion of TILs in standard prognostic panels has been limited. For example, some reports enumerate all CD3(+) cells, some count only cytotoxic CD8(+) T cells, and the criteria used to score tumors as TIL-positive or TIL-negative are inconsistent among studies. To address this limitation, we introduce a robust digital DNA-based assay, termed QuanTILfy, to count TILs and assess T cell clonality in tissue samples, including tumors. We demonstrate the clonal specificity of this approach by the diagnosis of T cell acute lymphoblastic leukemia and the accurate, sensitive, and highly reproducible measurement of TILs in primary and metastatic ovarian cancer. Our experiments demonstrate an association between higher TIL counts and improved survival among women with ovarian cancer, and are consistent with previous observations that the immune response against ovarian cancer is a meaningful and independent prognostic factor. Surprisingly, the TIL repertoire is diverse for all tumors in the study with no notable oligoclonal expansions. Furthermore, because variability in the measurement and characterization of TILs has limited their clinical utility as biomarkers, these results highlight the significant translational potential of a robust, standardizable DNA-based assay to assess TILs in a variety of cancer types.
| S-EPMC4026017 | biostudies-other
Project description:Cancer progression is marked by dysfunctional tumor-infiltrating lymphocytes (TIL) with high inhibitory receptor (IR) expression. Because IR blockade has led to clinical responses in some patients with non-small cell lung cancer (NSCLC), we investigated how IRs influenced CD8+ TIL function from freshly digested early-stage NSCLC tissues using a killing assay and intracellular cytokine staining after in vitro T-cell restimulation. Early-stage lung cancer TIL function was heterogeneous with only about one third of patients showing decrements in cytokine production and lytic function. TIL hypofunction did not correlate with clinical factors, coexisting immune cells (macrophages, neutrophils, or CD4+ T regulatory cells), nor with PD-1, TIGIT, TIM-3, CD39, or CTLA-4 expression. Instead, we found that the presence of the integrin αeβ7 (CD103), characteristic of tissue-resident memory cells (TRM), was positively associated with cytokine production, whereas expression of the transcription factor Eomesodermin (Eomes) was negatively associated with TIL function. These data suggest that the functionality of CD8+ TILs from early-stage NSCLCs may be influenced by competition between an antitumor CD103+ TRM program and an exhaustion program marked by Eomes expression. Understanding the mechanisms of T-cell function in the progression of lung cancer may have clinical implications for immunotherapy.
| S-EPMC6548666 | biostudies-literature
Project description:Microbial organisms play key roles in numerous physiological processes in the human body and have recently been shown to modify the response to cancer radiotherapy and immune checkpoint inhibitors. Here, we demonstrate that HLA molecules of both glioblastoma tissues as well as tumor cell lines present bacteria-specific peptides. This finding prompted us to examine whether tumor-infiltrating lymphocytes (TILs) recognize intratumoral microbiota. Indeed, bacterial peptides eluted from HLA-DR II molecules are recognized by both TILs, albeit weakly, and peripheral blood-derived memory CD4+ T cells, which, upon stimulation with bacterial peptides, also recognize several tumor antigens. Furthermore, using an unbiased antigen discovery approach for a TIL CD4+ T cell clone (TCC) we show that it recognizes a broad spectrum of peptides from pathogenic bacteria, commensal gut microbiota and also glioblastoma-related tumor antigens. These peptides were strongly stimulatory for bulk TILs and peripheral blood memory cells. Our data hint at how bacterial pathogens and bacterial gut microbiota can be involved in specific immune recognition of tumor antigens.
2023-02-20 | PXD036811 | Pride
Project description:Background: Tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T-cell therapies have demonstrated promising, though limited, efficacy against melanoma. Methods: We designed a model system to explore the efficacy of dual specific T cells derived from melanoma patient TILs by transduction with a Her2-specific CAR. Results: Metastatic melanoma cells in our biobank constitutively expressed Her2 antigen. CAR-TIL produced greater amounts of IFN compared with parental TIL, when co-cultured with Her2 expressing tumor lines, including autologous melanoma tumor lines, although no consistent increase in cytotoxicity by TIL was afforded by expression of a CAR. Results of an in vivo study in NSG mice demonstrated tumor shrinkage when CAR-TILs were used in an adoptive cell therapy protocol. Conclusion: Potential limitations of transduced TIL in our study included limited proliferative potential and a terminally differentiated phenotype, which would need addressing in further work before consideration of clinical translation.
| S-EPMC8186112 | biostudies-literature