Intraepithelial t cell

PURPOSE: The aim of this work was to evaluate the association of single nucleotide polymorphisms in TLR9 (-1486 T/C [rs187084], -1237T/C [rs5743836] and G2848A [rs352140]) with HPV infection, squamous intraepithelial lesions, and uterine cervical neoplasm in a Mexican population. Additionally, the peripheral expression of TLR9 was evaluated to evaluate the differences in the TLR9 expression associated with every genotype in the locus -1486 of the TLR9 gene. The serum concentration of TLR9 was evaluated in a randomly selected subsample...

Immune evasion of tumors poses a major challenge for immunotherapy. For human papillomavirus (HPV)-induced malignancies, multiple immune evasion mechanisms have been described, including altered expression of antigen processing machinery (APM) components. These changes can directly influence epitope presentation and thus T-cell responses against tumor cells. To date, the APM had not been studied systematically in a large array of HPV(+) tumor samples. Therefore in this study, systematic expression analysis of the APM was performed on the mRNA and protein level in a comprehensive collection of HPV16(+) cell lines...

Many basic properties of the T-cell receptor (TCR) repertoire require clarification, and the changes occurring in the TCR repertoire during carcinogenesis, especially during precancerous stages, remain unclear. This study used deep sequencing analyses to examine 41 gastric tissue samples at different pathological stages, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, early gastric cancer and matched adjacent tissues, to define the characteristics of the infiltrating TCRβ repertoire during gastric carcinogenesis...

Objective: To explore the value of histopathologic diagnosis after colposcopy for high-risk HPV16/18 positive patients with negative cytology or atypical squamous cells of undetermined significance (ASCUS) for early screening of cervical lesions. Methods: A retrospective study of cervical histopathologic diagnosis in the HPV16/18 positive patients received colposcopy evaluation before got the histology was carried out between January 2014 and January 2016. The cytology of the patients should be negative or ASCUS...

Peripheral Foxp3(+) regulatory T cells (pTregs) maintain immune homeostasis by controlling potentially harmful effector T cell responses toward dietary and microbial antigens. Although the identity of the T cell receptor (TCR) can impose commitment and functional specialization of T cells, less is known about how TCR identity governs pTreg development from conventional CD4(+) T cells. To investigate the extent to which TCR identity dictates pTreg fate, we used somatic cell nuclear transfer to generate a transnuclear (TN) mouse carrying a monoclonal TCR from a pTreg (pTreg TN mice)...

The small intestine contains CD4(+)CD8αα(+) double-positive intraepithelial T lymphocytes (DP IELs), which originate from intestinal CD4(+) T cells through downregulation of the transcription factor ThPOK and have regulatory functions. DP IELs are absent in germ-free mice, suggesting that their differentiation depends on microbial factors. We found that DP IEL numbers in mice varied in different vivaria, correlating with the presence of Lactobacillus reuteri This species induced DP IELs in germ-free mice and conventionally raised mice lacking these cells...

INTRODUCTION: Male genital lichen sclerosus (MGLSc) is an acquired, chronic, inflammatory skin disease that is associated with significant morbidity and squamous cell carcinoma of the penis (PSCC). However, some clinical, diagnostic and management controversies endure, including the relationship with penile intraepithelial neoplasia (PeIN). OBJECTIVES: To clarify clinical presentations, diagnostic approaches, histological findings, response to treatment and the relationship with PeIN...

The intestine is a major immune organ with several specialized lymphoid structures and immune cells. Among these are thymus-derived natural intraepithelial lymphocytes (IELs) that lack expression of the classical co-receptors CD4 or CD8αβ (double negative (DN)). Natural IELs are both αβ(+) and γδ(+) T cells that play important roles in the maintenance of the epithelial barrier at steady state and during inflammation. The transcription factor T-bet is essential for the peripheral development of natural IELs, but its role during thymic development has remained less clear...

A key feature of high-grade serous ovarian carcinoma (HGSOC) is frequent amplification of the 3q26 locus harboring PRKC-ι (PRKCI). Here, we show that PRKCI is also expressed in early fallopian tube lesions, called serous tubal intraepithelial carcinoma. Transgenic mouse studies establish PRKCI as an ovarian cancer-specific oncogene. Mechanistically, we show that the oncogenic activity of PRKCI relates in part to the up-regulation of TNFα to promote an immune-suppressive tumor microenvironment characterized by an abundance of myeloid-derived suppressor cells and inhibition of cytotoxic T-cell infiltration...

BACKGROUND: The present study investigated human papillomavirus (HPV) prevalence in anal and urine samples, and evaluated cytological findings among human immunodeficiency virus (HIV)-infected Japanese men who have sex with men (MSM). METHODS: A total of 148 patients were enrolled. Anal and urine samples were collected from each participant, and a HPV-DNA test and genotyping were performed using flow-through hybridization. In addition, anal cytology was evaluated based on Papanicolaou staining...

Esophageal squamous cell carcinoma (ESCC) is the most common esophageal cancer associated with poor prognosis and additional therapeutic strategies must be implemented to optimize ESCC treatment. Meanwhile, the important biologic role and potential prognostic and therapeutic implications of a tumors immunologic microenvironment (IM) have been recognized in various cancers.In order to investigate the contexture and the prognostic relevance of the IM in ESCC, we immunohistochemically evaluated the extent of overall/intraepithelial TILs (CD3+/CD8+) and of PD-1 / PD-L1 expression in a cohort of 125 therapy-naive ESCCs, additionally assessing PD-L1 copy number status via fluorescence in-situ hybridization...

Strong T cell receptor (TCR) signaling largely induces cell death during thymocyte development, whereas weak TCR signals induce positive selection. However, some T cell lineages require strong TCR signals for differentiation through a process termed agonist selection. The signaling relationships that underlie these three fates are unknown. RasGRP1 is a Ras activator required to transmit weak TCR signals leading to positive selection. Here, we report that, despite being dispensable for thymocyte clonal deletion, RasGRP1 is critical for agonist selection of TCRαβ(+)CD8αα intraepithelial lymphocyte (IEL) progenitors (IELps), even though both outcomes require strong TCR signaling...

Serrated lesions in the colorectum are currently predominantly classified as hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs) according to their morphology. However, the histological morphology and the molecular changes in the serrated lesions are still unclear. We performed immunohistochemistry for Ki67, p16INK4a, and WNT5A in human HPs (n=22), SSA/Ps (n=41), and TSAs (n=19). The distribution of Ki67 and p16INK4a positive cells in TSAs was different from that in HPs and SSA/Ps...

PROBLEM: APOBEC3G (A3G) is a cytidine deaminase that exhibits antiviral activity by introducing C-to-T hypermutation in viral DNA. We recently observed the distinct presence of C-to-T hypermutation of human papillomavirus DNA in uterine cervical intraepithelial neoplasia (CIN), suggesting the possible involvement of A3G in the mutation-inducing process. Consequently, we investigated the association of A3G expression with CIN progression in this study. METHOD OF STUDY: Patients who had undergone cervical conization due to CIN1 (n=11), CIN2 (n=9), CIN3 (n=12), and micro-invasive squamous cell carcinoma (n=2) were included...

In this updated systematic review and meta-analysis, we estimate the pooled prevalence of human papillomavirus (HPV) DNA and HPV type distribution in squamous cell carcinoma of the vulva (vulvar cancer) and vulvar intraepithelial neoplasia (VIN). PubMed, Embase and Cochrane Library databases were used to identify studies published between 1990 and 2015 and using a PCR-based or hybrid capture test to evaluate the presence of HPV DNA in vulvar cancer or VIN. Pooled estimates of the HPV prevalence with corresponding 95% confidence intervals (CI) were calculated based on a random effects model...

OBJECTIVE: Multiple solid cancers contain tertiary lymphoid organs (TLO). However, it is unclear whether they promote tumor rejection, facilitate tumor evasion, or simply whether they are a byproduct of chronic inflammation. We hypothesize that although chronic inflammation induces TLO formation, the tumor milieu can modulate TLO organization and functions in prostate cancer. Therefore, our study seeks to elucidate the cellular and molecular signatures in unique prostatectomy specimens from evanescent carcinoma patients to identify markers of cancer regression, which could be harnessed to modulate local immunosuppression or potentially enhance TLO function...

Most children with asthma have their disease easily controlled if low-dose inhaled corticosteroids (ICSs) are regularly and correctly administered. If a child presents with asthma which is apparently resistant to therapy with high-dose ICS and other controllers, then they have problematic severe asthma. However, in light of the UK National Review of Asthma Deaths, definitions of severe asthma based solely on the levels of prescribed treatment are too narrow. A detailed assessment of all such children should be performed...

TCRαβ(+)CD4(-)CD8α(+)CD8β(-) intestinal intraepithelial lymphocytes (CD8αα IELs) are an abundant population of thymus-derived T cells that protect the gut barrier surface. We sought to better define the thymic IEL precursor (IELp) through analysis of its maturation, localization and emigration. We defined two precursor populations among TCRβ(+)CD4(-)CD8(-) thymocytes by dependence on the kinase TAK1 and rigorous lineage-exclusion criteria. Those IELp populations included a nascent PD-1(+) population and a T-bet(+) population that accumulated with age...

BACKGROUND: Paget disease, Bowen disease, and malignant melanoma in situ are intraepidermal neoplasms, characterized by the presence of pagetoid scatter of atypical cells in the epidermis. This study reviewed the frequency of select histologic criteria to validate their usefulness in the histologic distinction between these entities. METHODS: One hundred forty-four specimens with the diagnosis of Bowen disease, 144 specimens with Paget disease (mammary and extramammary), and 144 specimens with malignant melanoma in situ were examined microscopically to define frequencies of select histologic criteria present in each disease...

The Ly49E receptor is preferentially expressed on murine innate-like lymphocytes, such as epidermal Vγ3 T cells, intestinal intraepithelial CD8αα(+) T lymphocytes, and CD49a(+) liver natural killer (NK) cells. As the latter have recently been shown to be distinct from conventional NK cells and have innate lymphoid cell type 1 (ILC1) properties, we investigated Ly49E expression on intestinal ILC populations. Here, we show that Ly49E expression is very low on known ILC populations, but it can be used to define a previously unrecognized intraepithelial innate lymphoid population...