Correction: Single-cell RNA sequencing of human breast tumour-infiltrating immune cells reveals a γδ T-cell subtype associated with good clinical outcome.
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ABSTRACT:
SUBMITTER: Boufea K
PROVIDER: S-EPMC9748721 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
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Correction: Single-cell RNA sequencing of human breast tumour-infiltrating immune cells reveals a γδ T-cell subtype associated with good clinical outcome.
Boufea Katerina K Gonzalez-Huici Victor V Lindberg Marcus M Olova Nelly N NN Symeonides Stefan S Oikonomidou Olga O Batada Nizar N NN
Life science alliance 20221213 2
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Project description:The association of increased levels of tumour-infiltrating gamma-delta (γδ) T cells with favorable prognosis across many cancer types and their ability to recognize stress antigens in an MHC unrestricted manner has led to an increased interest in exploiting them for cancer immunotherapy. We performed single-cell RNA sequencing (scRNA-seq) of peripheral blood γδ T cells from healthy adult donors and from fresh tumour biopsies of breast cancer patients. We identified five γδ T cells subtypes in blood and three subtypes of γδ T cells in breast tumour. These subtypes differed in the expression of genes contributing to effector functions such as antigen presentation, cytotoxicity, and IL17A and IFNγ production. Compared with the blood γδ T cells, the breast tumour-infiltrating γδ T cells were more activated, expressed higher levels of cytotoxic genes, yet were immunosuppressed. One subtype in the breast tumour that was IFNγ-positive had no obvious similarity to any of the subtypes observed in the blood γδ T cell and was the only subtype associated with improved overall survival of breast cancer patients. Taken together, our study has identified markers of subtypes of human blood γδ T cells and uncovered a tumour-infiltrating γδ T cells subtype associated improved overall cancer survival.
| S-EPMC7723295 | biostudies-literature
Project description: Not available
| S-EPMC8679836 | biostudies-literature
Project description:BackgroundRegulatory T cells (Tregs) are commonly identified by expression of the transcription factor FOXP3 and are conventionally thought to promote cancer progression by suppressing anti-tumour immune responses. We examined the relationship between FOXP3(+) tumour-infiltrating lymphocytes (TIL) and prognosis in oestrogen receptor (ER)-negative breast cancer, a tumour subtype with poor clinical outcome in which TIL are abundant.MethodsFOXP3(+) and CD8(+) TIL were assessed by immunohistochemistry in a cohort of 175 ER- breast tumours. Results were confirmed in an independent data set of 78 ER- breast tumours with publically available gene expression data.ResultsHigh FOXP3(+) TIL levels were strongly associated with prolonged recurrence-free survival (HR=0.461, P=0.0002), particularly among basal-like tumours (HR=0.280, P=0.0001), for which FOXP3 status was independent of standard prognostic factors. Over 75% of FOXP3(+) TIL in triple negative breast tumours displayed a conventional CD4(+)CD25(+) Treg phenotype. Importantly, FOXP3(+) TIL were positively correlated with CD8(+) (cytotoxic) T cells (r(s)=0.76, P<0.0001), and were prognostically insignificant in tumours with low levels of CD8(+) TIL. These observations were confirmed in an independent cohort.ConclusionIn contrast with current dogma, we show for the first time that FOXP3(+) TIL are associated with robust anti-tumour immunity and favourable prognosis in ER- breast cancer.
| S-EPMC3553524 | biostudies-literature
Project description:BackgroundHuman papillomavirus (HPV)-positive oropharyngeal cancer (OPSCC) is associated with improved survival compared with HPV-negative disease. However, a minority of HPV-positive patients have poor prognosis. Currently, there is no generally accepted strategy for identifying these patients.MethodsWe retrospectively analysed 270 consecutively treated OPSCC patients from three centres for effects of clinical, pathological, immunological, and molecular features on disease mortality. We used Cox regression to examine associations between factors and OPSCC death, and developed a prognostic model for 3-year mortality using logistic regression analysis.ResultsPatients with HPV-positive tumours showed improved survival (hazard ratio (HR), 0.33 (0.21-0.53)). High levels of tumour-infiltrating lymphocytes (TILs) stratified HPV-positive patients into high-risk and low-risk groups (3-year survival; HPV-positive/TIL(high)=96%, HPV-positive/TIL(low)=59%). Survival of HPV-positive/TIL(low) patients did not differ from HPV-negative patients (HR, 1.01; P=0.98). We developed a prognostic model for HPV-positive tumours using a 'training' cohort from one centre; the combination of TIL levels, heavy smoking, and T-stage were significant (AUROC=0·87). This model was validated on patients from the other centres (detection rate 67%; false-positive rate 5.6%; AUROC=0·82).InterpretationOur data suggest that an immune response, reflected by TIL levels in the primary tumour, has an important role in the improved survival seen in most HPV-positive patients, and is relevant for the clinical evaluation of HPV-positive OPSCC.
| S-EPMC3899750 | biostudies-literature
Project description:γδ T-cells contribute to the immune response against many tumor types through their direct cytolytic functions and their capacity to recruit and regulate the biological functions of other immune cells. As potent effectors of the anti-tumor immune response, they are considered an attractive therapeutic target for immunotherapies, but their presence and abundance in the tumor microenvironment are not routinely assessed in patients with cancer. Here, we validated an antibody for immunohistochemistry analysis that specifically detects all γδ T-cell subpopulations in healthy tissues and in the microenvironment of different cancer types. Tissue microarray analysis of breast, colon, ovarian, and pancreatic tumors showed that γδ T-cell density varies among cancer types. Moreover, the abundance of γδ tumor-infiltrating lymphocytes was variably associated with the outcome depending on the cancer type, suggesting that γδ T-cell recruitment is influenced by the context. These findings also suggest that γδ T-cell detection and analysis might represent a new and interesting diagnostic or prognostic marker.
| S-EPMC7348937 | biostudies-literature
Project description:Background and purposeMeasuring rectal tumour response to radiation is pivotal to restaging patients and for possibly stratification to a watch-and-wait strategy. Recognizing the importance of the tumour microenvironment, we investigated a less explored quantitative imaging marker assessing tumour blood flow (BF) for its potential to predict overall survival (OS).Materials and methods24 rectal cancer patients given curative-intent neoadjuvant radiotherapy underwent a multi-echo dynamic magnetic resonance imaging (MRI) sequence with gadolinium contrast for quantification of tumour BF before either 25x2 Gy (n = 18) with concomitant chemotherapy or 5x5 Gy (n = 6). CD34 staining of excised tumour tissue was performed and baseline blood samples were analysed for lactate dehydrogenase (LDH) and angiopoietin-2 (ANGPT-2). Tumour volumes were measured before and after treatment. After subsequent surgery, ypTN scoring assessed tumour response. Cox regression for 5-year OS analysis and t-test for group comparisons were performed.ResultsThe change in tumour BF (ΔBF) during neoadjuvant radiotherapy was a significant marker of OS, whereas tumour stage and volume were not related to OS. All patients with >20 % decline in BF were long-term survivors. Separating cases in two groups based on ΔBF revealed that patients with increase or a low decrease had higher baseline LDH (p = 0.032) and ANGPT-2 (p = 0.028) levels.ConclusionMRI-assessed tumour ΔBF during neoadjuvant treatment is a significant predictor of OS in rectal cancer patients, making ΔBF a potential quantitative imaging biomarker for treatment stratification. Blood LDH and ANGPT-2 indicate that non-responding tumours may have a hypoxic microenvironment resistant to radiotherapy.
| S-EPMC9883255 | biostudies-literature
Project description:BackgroundMetastatic breast cancer poses great challenge in cancer treatment. N-dihydrogalactochitosan (GC) is a novel immunoadjuvant that stimulates systemic immune responses when administered intratumourally following local tumour ablation. A combination of photothermal therapy (PTT) and GC, referred to as localized ablative immunotherapy (LAIT), extended animal survival and generates an activated B cell phenotype in MMTV-PyMT mouse mammary tumour microenvironment (TME). However, how T cell populations respond to LAIT remains to be elucidated.MethodsUsing depletion antibodies, we studied the contributions of CD8+ and CD4+ T cells to the therapeutic effect of LAIT. Using single-cell RNA-sequencing (scRNAseq), we analysed tumour-infiltrating T cell heterogeneity and dissected their transcriptomes upon treatments of PTT, GC, and LAIT (PTT+GC).ResultsLoss of CD8+ T cells after LAIT abrogated the therapeutic benefits of LAIT. Ten days after treatment, proportions of CD8+ and CD4+ T cells in untreated TME were 19.2% and 23.0%, respectively. Upon LAIT, both proportions were increased to 25.5% and 36.2%, respectively. In particular, LAIT increased the proportions of naïve and memory cells from a resting state to an activated state. LAIT consistently induced the expression of co-stimulatory molecules, type I IFN responsive genes, and a series of antitumor cytokines, Ifng, Tnf, Il1, and Il17 in CD8+ and CD4+ T cells. LAIT also induced immune checkpoints Pdcd1, Ctla4, and Lag3 expression, consistent with T cell activation. Relevant to clinical translation, LAIT also upregulated genes in CD8+ and CD4+ T cells that positively correlated with extended survival of breast cancer patients.ConclusionsOverall, our results reveal that LAIT prompts immunological remodelling of T cells by inducing broad proinflammatory responses and inhibiting suppressive signalling to drive antitumour immunity.
| S-EPMC9270578 | biostudies-literature
Project description:BackgroundThere is evidence that some ovarian tumours evoke an immune response, which can be assessed by tumour infiltrating lymphocytes (TILs). To facilitate adoption of TILs as a clinical biomarker, a standardised method for their H&E visual evaluation has been validated in breast cancer.MethodsWe sought to investigate the prognostic significance of TILs in a study of 953 invasive epithelial ovarian cancer tumour samples, both primary and metastatic, from 707 patients from the prospective population-based SEARCH study. TILs were analysed using a standardised method based on H&E staining producing a percentage score for stromal and intratumoral compartments. We used Cox regression to estimate hazard ratios of the association between TILs and survival.ResultsThe extent of stromal and intra-tumoral TILs were correlated in the primary tumours (n = 679, Spearman's rank correlation = 0.60, P < 0.001) with a similar correlation in secondary tumours (n = 224, Spearman's rank correlation = 0.62, P < 0.001). There was a weak correlation between stromal TIL levels in primary and secondary tumour samples (Spearman's rank correlation = 0.29, P < 0.001) and intra-tumoral TIL levels in primary and secondary tumour samples (Spearman's rank correlation = 0.19, P = 0.0094). The extent of stromal TILs differed between histotypes (Pearson chi2 (12d.f.) 54.1, P < 0.0001) with higher levels of stromal infiltration in the high-grade serous and endometriod cases. A significant association was observed for higher intratumoral TIL levels and a favourable prognosis (HR 0.74 95% CI 0.55-1.00 p = 0.047).ConclusionThis study is the largest collection of epithelial ovarian tumour samples evaluated for TILs. We have shown that stromal and intratumoral TIL levels are correlated and that their levels correlate with clinical variables such as tumour histological subtype. We have also shown that increased levels of both intratumoral and stromal TILs are associated with a better prognosis; however, this is only statistically significant for intratumoral TILs. This study suggests that a clinically useful immune prognostic indicator in epithelial ovarian cancer could be developed using this technique.
| S-EPMC5607562 | biostudies-literature
Project description:BackgroundT lymphocyte infiltration has been detected in glioma, although its significance remains unclear. The purpose of the present study was to explore the prognostic value of CD4(+) and CD8(+) tumour-infiltrating lymphocytes (TILs) in glioma, and the prognostic value of infiltrating Forkhead box protein 3 (FoxP3(+)) regulatory T cells were also investigated.MethodsCD4(+), FoxP3(+) and CD8(+) TILs were assessed by immunohistochemical staining of tissue microarray cores from 284 gliomas. Kaplan-Meier analysis and Cox proportional hazards models were used to examine the survival function of these TILs in 90 glioblastoma patients.ResultsThe number of CD8(+) TILs was inversely correlated with tumour grade (P=0.025), whereas the number of CD4(+) TILs was positively correlated with tumour grade (P=0.002). FoxP3(+) TILs were only observed in glioblastomas, but not in low-grade astrocytomas or oligodendroglial tumours. Among patients with glioblastoma, none of CD4(+) TILs, FoxP3(+) TILs and CD8(+) TILs alone was significantly associated with patient prognosis. However, the presence of high CD4(+) and low CD8(+) TIL levels was an independent predictor of poor progress-free survival (multivariate hazard ratio (HR) 1.618, 95% confidence interval (CI) 1.245-2.101, P<0.001) and poor overall survival (multivariate HR 1.508, 95% CI 1.162-1.956, P=0.002). Moreover, pseudoprogression was more often found in patients with high CD4(+) TILs and high CD8(+) TILs.ConclusionsThe combination of CD4(+) and CD8(+) TILs is a predictor of clinical outcome in glioblastoma patients, and a high level of CD4(+) TILs combined with low CD8(+) TILs was associated with unfavourable prognosis.
| S-EPMC4021514 | biostudies-literature
Project description:Sequencing of RNAs (RNA-Seq) has revolutionized the field of transcriptomics, but the reads obtained often contain errors. Read error correction can have a large impact on our ability to accurately assemble transcripts. This is especially true for de novo transcriptome analysis, where a reference genome is not available. Current read error correction methods, developed for DNA sequence data, cannot handle the overlapping effects of non-uniform abundance, polymorphisms and alternative splicing. Here we present SEquencing Error CorrEction in Rna-seq data (SEECER), a hidden Markov Model (HMM)-based method, which is the first to successfully address these problems. SEECER efficiently learns hundreds of thousands of HMMs and uses these to correct sequencing errors. Using human RNA-Seq data, we show that SEECER greatly improves on previous methods in terms of quality of read alignment to the genome and assembly accuracy. To illustrate the usefulness of SEECER for de novo transcriptome studies, we generated new RNA-Seq data to study the development of the sea cucumber Parastichopus parvimensis. Our corrected assembled transcripts shed new light on two important stages in sea cucumber development. Comparison of the assembled transcripts to known transcripts in other species has also revealed novel transcripts that are unique to sea cucumber, some of which we have experimentally validated. Supporting website: http://sb.cs.cmu.edu/seecer/.
| S-EPMC3664804 | biostudies-literature