Dataset Information

Immune Phenotypes of Nasopharyngeal Cancer.

ABSTRACT: Nasopharyngeal cancer (NPC) features intralesional immune cells, but data are lacking on presence/distribution of T-cells and dendritic cells (DCs). Based on intralesional distribution of lymphocytes, a series of NPC biopsies (n = 48) were classified into "inflamed", "excluded", and "deserted" phenotypes. In addition, CD8+ T-cells and CD207+ DCs were quantified. The data were analyzed in relation to Epstein-Barr virus-encoded small RNA (EBER), Epstein-Barr virus (EBV) DNA, and survival. Separately, data on gene expression from a public database were analyzed. 61.7% of NPC lesions were "inflamed", 29.8% were "excluded", and 8.5% were "deserted". While CD8+ cells were present in cancer cell areas and in surrounding stroma, CD207+ cells were observed largely in cancer cell areas. High CD8+ T-cell presence was associated with EBV+ disease, but no such pattern was observed for CD207+ DCs. There was a difference in disease-free survival in favor of "inflamed" over "excluded" NPC. Gene expression analysis revealed differences between NPC and control tissue (e.g., with regard to interferon activity) as well as between subgroups of NPC based on CD8 expression (high vs. low). In conclusion, NPC lesions are heterogeneous with regard to distribution of CD8+ T-cells and CD207+ DCs. NPC can be classified into immune phenotypes that carry prognostic information. CD207+ DCs may represent a target for immunotherapy with potential to facilitate the antigen cross-presentation necessary to execute cytotoxic T-lymphocyte responses.

SUBMITTER: Nilsson JS

PROVIDER: S-EPMC7699205 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Immune Phenotypes of Nasopharyngeal Cancer.

Nilsson Johan S JS Sobti Aastha A Swoboda Sabine S Erjefält Jonas S JS Forslund Ola O Lindstedt Malin M Greiff Lennart L

Cancers 20201118 11

Nasopharyngeal cancer (NPC) features intralesional immune cells, but data are lacking on presence/distribution of T-cells and dendritic cells (DCs). Based on intralesional distribution of lymphocytes, a series of NPC biopsies (<i>n</i> = 48) were classified into "inflamed", "excluded", and "deserted" phenotypes. In addition, CD8+ T-cells and CD207+ DCs were quantified. The data were analyzed in relation to Epstein-Barr virus-encoded small RNA (EBER), Epstein-Barr virus (EBV) DNA, and survival. S ...[more]

PMID: 33218184

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Project description:Nasopharyngeal cancer (NPC) is a malignant tumor. In a recent publication, we described the presence and distribution of CD8+ T cells in NPC and used the information to identify 'inflamed', 'immune-excluded', and 'desert' immune phenotypes, where 'inflamed' and 'immune-excluded' NPCs were correlated with CD8 T cell infiltration and survival. Arguably, more detailed and, in particular, spatially resolved data are required for patient stratification and for the identification of new treatment targets. In this study, we investigate the phenotype of CD45+ leukocytes in the previously analyzed NPC samples by applying multiplexed tissue analysis to assess the spatial distribution of cell types and to quantify selected biomarkers. A total of 47 specified regions-of-interest (ROIs) were generated based on CD45, CD8, and PanCK morphological staining. Using the GeoMx® Digital Spatial Profiler (DSP), 49 target proteins were digitally quantified from the selected ROIs of a tissue microarray consisting of 30 unique NPC biopsies. Protein targets associated with B cells (CD20), NK cells (CD56), macrophages (CD68), and regulatory T cells (PD-1, FOXP3) were most differentially expressed in CD45+ segments within 'immune-rich cancer cell islet' regions of the tumor (cf. 'surrounding stromal leukocyte' regions). In contrast, markers associated with suppressive populations of myeloid cells (CD163, B7-H3, VISTA) and T cells (CD4, LAG3, Tim-3) were expressed at a higher level in CD45+ segments in the 'surrounding stromal leukocyte' regions (cf. 'immune-rich cancer cell islet' regions). When comparing the three phenotypes, the 'inflamed' profile (cf. 'immune-excluded' and 'desert') exhibited higher expression of markers associated with B cells, NK cells, macrophages, and myeloid cells. Myeloid markers were highly expressed in the 'immune-excluded' phenotype. Granulocyte markers and immune-regulatory markers were higher in the 'desert' profile (cf. 'inflamed' and 'immune-excluded'). In conclusion, this study describes the spatial heterogeneity of the immune microenvironment in NPC and highlights immune-related biomarkers in immune phenotypes, which may aid in the stratification of patients for therapeutic purposes.

Project description:BackgroundNasopharyngeal cancer is endemic in a few well-defined populations. The prognosis for advanced nasopharyngeal cancer is poor, but early-stage disease is curable and a high survival rate can be achieved. Screening for early-stage disease could lead to improved outcomes. Epstein-Barr virus (EBV) serology and nasopharyngoscopy are most commonly used for screening. The efficacy and true benefit of screening remain uncertain due to potential selection, lead-time and length-time biases.ObjectivesTo determine the effectiveness of screening of asymptomatic individuals by EBV serology and/or nasopharyngoscopy in reducing the mortality of nasopharyngeal cancer compared to no screening. To assess the impact of screening for nasopharyngeal cancer on incidence, survival, adverse effects, cost-effectiveness and quality of life.Search methodsThe Cochrane Ear, Nose and Throat Disorders Group (CENTDG) Trials Search Co-ordinator searched the CENTDG Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 6); PubMed; EMBASE; CINAHL; Web of Science; Clinicaltrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 6 July 2015.Selection criteriaRandomised controlled trials (RCT) and controlled clinical trials (CCT) evaluating screening for nasopharyngeal cancer versus no screening. Randomisation either by clusters or individuals was acceptable.Data collection and analysisWe used the standard methodological procedures expected by The Cochrane Collaboration. Our primary outcome measure was nasopharyngeal cancer-specific mortality. Secondary outcomes were incidence of nasopharyngeal cancer by stage and histopathological classification at diagnosis, survival (two-year, three-year, five-year and 10-year), harms of screening (physical and psychosocial), quality of life (via validated tools such as the SF-36 and patient satisfaction), cost-effectiveness and all-cause mortality.Main resultsWe identified no trials that met the review inclusion criteria. We retrieved 31 full-text studies for further investigation following the search. However, none met the eligibility criteria for a RCT or CCT investigation on the efficacy of screening for nasopharyngeal cancer.Authors' conclusionsNo data from RCTs or CCTs are available to allow us to determine the efficacy of screening for nasopharyngeal cancer, or the cost-effectiveness and cost-benefit of a screening strategy. High-quality studies with long-term follow-up of mortality and cost-effectiveness are needed.

Dataset Information

Immune Phenotypes of Nasopharyngeal Cancer.

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Immune Phenotypes of Nasopharyngeal Cancer.

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