Evaluation of T, B and natural killer lymphocyte in the cervical stroma of HIV-positive and negative patients with cervical intraepithelial neoplasia

Lucena, Adriana A.S.; Guimarães, Mirian Viviane Maciel Barros; Michelin, Márcia Antoniazi; Lodi, Claudia Teixeira Costa; Lima, Maria Inês Miranda; Murta, Eddie Fernando Cândido; Melo, Victor Hugo

doi:10.1016/j.imlet.2015.10.016

Cited by 11 publications

(9 citation statements)

References 26 publications

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“…Cell-mediated immunity of an individual is considered to be a vital mechanism in protection against the virus and elimination of virus-infected cells. The activation of CD4 + T cells and consequently synthesis of cytokines are essential in the immune response because these mediators could activate or inhibit other cells types including cytotoxic CD8 + T cells (19). Cytotoxic CD8 + T cell infiltrates appear to be principal effectors in eliminating HPV infected pre-neoplastic human cervical epithelial cells and severe dysplastic cells (20).…”

Section: Discussionmentioning

confidence: 99%

Nocardia Rubra Cell Wall Skeleton Up-Regulates T Cell Subsets and Inhibits PD-1/PD-L1 Pathway to Promote Local Immune Status of Patients With High-Risk Human Papillomavirus Infection and Cervical Intraepithelial Neoplasia

Chen

Zhang²,

Zhao

et al. 2021

Front. Immunol.

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The Nocardia rubra cell wall skeleton (Nr-CWS) for external use is an immune enhancer, which has been widely used in human cervix diseases such as cervical erosion, but the mechanism of Nr-CWS enhancing immunity is still unclear. The purpose of this study was to explore the effect and mechanism of Nr-CWS on the local immune status of cervical tissue in patients with high-risk human papillomavirus (HR-HPV) infection and cervical precancerous lesion, cervical intraepithelial neoplasia (CIN). The recruited patients with HR-HPV infection and CIN were treated with Nr-CWS. The specimens were taken from these patients before and after local application of Nr-CWS respectively. The normal control specimens were tested simultaneously. Serial section analysis of immunohistochemistry and co-expression analysis were performed to characterize populations of T cells and the expressions of programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1). The levels of cytokines in local cervical tissue were also detected. Nr-CWS significantly increased T cells including CD4+, CD8+ T cells, and reduced the expression of PD-L1 in the patients’ local cervical tissues. Co-expression analyses showed that the proportions of PD-1+CD4+ cells in CD4+ T cells and PD-1+CD8+ cells in CD8+ T cells decreased after Nr-CWS application. Furthermore, the increase in the number of immune cells was accompanied by increased pro-inflammatory cytokines interleukin-12 (IL-12), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and decreased suppressive cytokine IL-10. The results indicate that Nr-CWS, as an immunotherapeutic agent for HR-HPV infection and CIN, plays an immune promoting role related to the upregulation of T cell subsets and the inhibition of PD-1/PD-L1 pathway.

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Section: Discussionmentioning

confidence: 99%

Nocardia Rubra Cell Wall Skeleton Up-Regulates T Cell Subsets and Inhibits PD-1/PD-L1 Pathway to Promote Local Immune Status of Patients With High-Risk Human Papillomavirus Infection and Cervical Intraepithelial Neoplasia

Chen

Zhang²,

Zhao

et al. 2021

Front. Immunol.

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“…20 Despite the relevance of the cytotoxic functions of Natural killer cells and CTLs in the control of CIN progression and cancer, few reports were directed to investigate the density of NK cells in cervical tissues samples. 13,14,18,24,25 Our study demonstrated an important increase in the number of NK-like cells in cervical tissues from patients with CIN and invasive cancer compared with tissues obtained from women without cellular abnormalities. One work based on the semi-quantitative analysis of NK cells detected by IHC in twenty-three cervical tissues observed the presence of NK cells in 2 out of 5 (40%) normal controls, in 5 out of 6 (84%) HPV-positive samples and in 9 out of 12 (75%) CIN tissues, with predominant location of NK cells in the sub-epithelial stroma.…”

Section: Discussionmentioning

confidence: 66%

“…12 Despite the pivotal role of cytotoxic immune cells such as Natural killer in the host resistance to viruses and tumors, evaluation of the NK densities directly from cervical pre-neoplastic and neoplastic tissues has been only investigated in relatively few studies. [13][14][15][16][17][18] Therefore, the aim of this study was to perform a quantitative analysis of NK cells and T-lymphocytes positive for GranzB directly from lesioned areas of cervical tissues with SILs and invasive cancer. Since we aimed to evaluate the precise number of cytotoxic cells in progressive stages of cervical lesions, our study analyzed pre-neoplastic samples categorized as CINI, II and III lesions.…”

Section: Introductionmentioning

confidence: 99%

Assessment of natural killer cells in tissues from patients with cervical abnormalities

Vágó¹,

Camargos²,

Silva³

et al. 2018

OGIJ

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Objectives: The cellular immune system mediated by cytotoxic T lymphocytes (CTLs) and Natural killer (NK) cells are thought to play an important role in the ultimate decline of Squamous Intraepithelial Lesions (SILs). In this study, Natural killer and granzyme B (GranzB) positive T-cells were quantitatively evaluated in cervical tissue-samples obtained from women exhibiting invasive cancer (n=5) and progressive grades of Cervical Intraepithelial, (CIN)I (n=5), CINII (n=5) and CINIII (n=5), in addition to five normal controls. Methods: The precise number of cervical T-cells subpopulations, positive for the cytotoxic marker GranzB was determined by performing a morphometric analysis of positive cells detected by Immunohistochemistry, (i) in the entire area of lesioned epithelium from CIN samples and, (ii) within the invasive epithelial areas and in zones of surrounding lymphocyte infiltration in cervical cancer tissues. Results: In normal cervix, a lower density of GranzB+ cells was observed, in comparison with the number of those cells detected in pre-neoplastic and cervical cancer tissues. Large granzyme B positive cells, exhibiting morphological aspects of Natural killer cells (NK-like cells) could be easily observed within the lesioned epithelium in CIN samples, as well as within the tumor nests and in the surrounding stroma, in invasive cervical cancer tissues. The number of GranzB+-cytotoxic T lymphocytes exceeded the number of NK-like cells in both, CIN tissues and invasive cancer. Increased densities of GranzB+ cells were observed in CIN samples, with an important prevalence of these cytotoxic cells in CINIII samples. Conclusion: Our results indicate that the morphometric evaluation of GranzB+ cells' number is a quantitative and effective approach to determine the number of NKlike cells and cytotoxic T lymphocytes in cervical tissues. Our findings also suggest that these immune-cells are possibly involved in the cervix surveillance against the cervical lesion development.

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“…Due to a limited number of chronic HR-HPV samples, we could not group according to cytological categories, and therefore, one limitation is that the HR-HPV chronic group constitutes a mixed group for cytology. Studies show that HIV positive women have more CD8+ lymphocytes in HPV-positive cervical lesions, compared with HIV negative women [ 45 , 46 ]. Therefore, we cannot rule out the possibility that HIV infection may be a bias in the analyses.…”

Section: Discussionmentioning

confidence: 99%

Changes in the Proteome in the Development of Chronic Human Papillomavirus Infection—A Prospective Study in HIV Positive and HIV Negative Rwandan Women

Bienvenu

Mukanyangezi

Rulisa

et al. 2021

Cancers

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Background: Effects on the proteome when a high risk (HR)-HPV infection occurs, when it is cleared and when it becomes chronic were investigated. Moreover, biomarker panels that could identify cervical risk lesions were assessed. Methods: Cytology, HPV screening and proteomics were performed on cervical samples from Rwandan HIV+ and HIV- women at baseline, at 9 months, at 18 months and at 24 months. Biological pathways were identified using the String database. Results: The most significantly affected pathway when an incident HR-HPV infection occurred was neutrophil degranulation, and vesicle-mediated transport was the most significantly affected pathway when an HR-HPV infection was cleared; protein insertion into membrane in chronic HR-HPV lesions and in lesions where HR-HPVs were cleared were compared; and cellular catabolic process in high-grade lesions was compared to that in negative lesions. A four-biomarker panel (EIF1; BLOC1S5; LIMCH1; SGTA) was identified, which was able to distinguish chronic HR-HPV lesions from cleared HR-HPV/negative lesions (sensitivity 100% and specificity 91%). Another four-biomarker panel (ERH; IGKV2-30; TMEM97; DNAJA4) was identified, which was able to distinguish high-grade lesions from low-grade/negative lesions (sensitivity 100% and specificity 81%). Conclusions: We have identified the biological pathways triggered in HR-HPV infection, when HR-HPV becomes chronic and when cervical risk lesions develop. Moreover, we have identified potential biomarkers that may help to identify women with cervical risk lesions.

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Evaluation of T, B and natural killer lymphocyte in the cervical stroma of HIV-positive and negative patients with cervical intraepithelial neoplasia

Cited by 11 publications

References 26 publications

Nocardia Rubra Cell Wall Skeleton Up-Regulates T Cell Subsets and Inhibits PD-1/PD-L1 Pathway to Promote Local Immune Status of Patients With High-Risk Human Papillomavirus Infection and Cervical Intraepithelial Neoplasia

Nocardia Rubra Cell Wall Skeleton Up-Regulates T Cell Subsets and Inhibits PD-1/PD-L1 Pathway to Promote Local Immune Status of Patients With High-Risk Human Papillomavirus Infection and Cervical Intraepithelial Neoplasia

Assessment of natural killer cells in tissues from patients with cervical abnormalities

Changes in the Proteome in the Development of Chronic Human Papillomavirus Infection—A Prospective Study in HIV Positive and HIV Negative Rwandan Women

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