ORIGINAL ARTICLE: Regulatory T Cells in a Spectrum of HPV‐Induced Cervical Lesions: Cervicitis, Cervical Intraepithelial Neoplasia and Squamous Cell Carcinoma

Adurthi, Sreenivas; Krishna, Sudhir; Mukherjee, Geetashree; Bafna, U. D.; Devi, U. K.; Jayshree, R. S.

doi:10.1111/j.1600-0897.2008.00590.x

Cited by 52 publications

(65 citation statements)

References 37 publications

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“…There are observations that those cells may be rendered tolerant by molecules present in tumor microenviroment [34,35]. Cervical tumors are marked by the presence of an immune regulatory microenvironment characterized by increased production of IL10 and TGFβ and decreased production of IL2 [31]. In addition, as we observed in this study, the presence of regulatory T cells may suggest a role of these cells in the induction of anergy of CD8+ cells.…”

Section: Discussionsupporting

confidence: 68%

“…It is of interest that elevated ORs were present when comparing SCC with lesions of all grades, suggesting that this is a phenomenon associated with invasion and not with persistent infection or development of precursor lesions. Given the fact that CD8+ cells presented the highest coefficient variation, and that there was lack of agreement when the dispersion of the measurements was compared, we also estimated the ORs using the counting conducted by each pathologist to estimate the average number of cells/mm 2 [14,15,30,31]. However since the confidence intervals were wide, studies with bigger sample size may help to confirm the accuracy of our observation.…”

Section: Discussionmentioning

confidence: 97%

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Location and Density of Immune Cells in Precursor Lesions and Cervical Cancer

Bedoya

Jaramillo

Baena

et al. 2012

Cancer Microenvironment

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Only a small proportion of women infected with Human Papillomavirus (HPV) develop cervical cancer. Host immune response seems to play a role eliminating the viral infection and preventing progression to cancer. Characterization of tumor infiltrating lymphocytes (TILs) in cervical pre-neoplastic lesions and cervical cancer may be helpful to understand the mechanisms that mediate this protection. The aim of this study was to determine if there are differences in the localization and density (cells/mm 2 ) of CD8+ T-cells, CD4+ T-cells and Tregs (CD25 + Foxp3+) in cervical pre-neoplastic lesions and cervical cancer. Immunohistochemical analysis of sections of 96 (26 CIN1, 21 CIN2, 25 CIN3, and 24 SCC) samples revealed that regardless of CIN grades, CD8+ T-cells are more abundant than CD4+, CD25+ and Foxp3+ cells in both the stroma and epithelium. There was a higher density of CD8+ cells in the stroma of cervical cancer compared to CIN3 (OR 0 4.20, 95% CI 1.2-15), CIN2 (OR 0 7.86, 95% CI 1.7-36.4) and CIN1 (OR 0 4.25, 95% CI 1.1-17). Studies evaluating whether these cells are recruited before or after cancer progression will be helpful to understand the role of these cells in the natural history of HPV-induced lesions.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 97%

Location and Density of Immune Cells in Precursor Lesions and Cervical Cancer

Bedoya

Jaramillo

Baena

et al. 2012

Cancer Microenvironment

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“…There is increased Foxp3 + Treg infiltration following hrHPV infection. Recent studies have highlighted the role of hrHPV-specific Treg generation induced by hrHPV infection and CIN progression (42). Tregs specific for the E6 and E7 antigens have been detected in high-grade squamous intraepithelial lesion (HSIL)-infiltrating lymphocytes (43), and there are several mechanisms that contribute to their generation and recruitment.…”

Section: Interplay Between Treg Cells and Hrhpv Infection Tregs (Cd4mentioning

confidence: 99%

“…HPV16, 18,31,33,35,39,45,51,52,56,58,59, 68 and 69 are classified as the hrHPVs (5). HPV6, 11,40,42,54,55,61,62,64,71,72,81,83 and 84 are classified as the low-risk HPVs (6). HPV16 and 18 are the most common types, accounting for ~70% of cervical cancers around the world (7).…”

Section: Introductionmentioning

confidence: 99%

Effect of human papillomavirus infection on the immune system and its role in the course of cervical cancer

et al. 2015

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Abstract. Human papillomavirus (HPV) is widely known as a cause of cervical intraepithelial neoplasia (CIN) and cervical cancer. The mechanisms involved have been studied by numerous studies. The integration of the virus genome into the host cells results in the abnormal regulation of cell cycle control. HPV can also induce immune evasion of the infected cells, which enable the virus to be undetectable for long periods of time. The induction of immunotolerance of the host's immune system by the persistent infection of HPV is one of the most important mechanisms for cervical lesions. The present review elaborates on the roles of several types of immune cells, such as macrophages and natural killer cells, which are classified as innate immune cells, and dendritic cells (DCs), cluster of differentiation (CD)4 + /CD8 + T cells and regulatory T cells, which are classified as adaptive immune cells. HPV infection could effect the differentiation of these immune cells in a unique way, resulting in the host's immune tolerance to the infection. The immune system modifications induced by HPV infection include tumor-associated macrophage differentiation, a compromised cellular immune response, an abnormal imbalance between type 1 T-helper cells (Th1) and Th2 cells, regulatory T cell infiltration, and downregulated DC activation and maturation. To date, numerous types of preventative vaccines have been created to slow down carcinogenesis. Immune response activation-based therapeutic vaccine is becoming more and more attractive for the treatment of HPV-associated diseases.

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“…Infection progression has been associated with several factors, including the persistence of HPV, the presence of high-risk oncogenic HPV types, high viral load, integration of viral DNA, and E6 and E7 viral oncoprotein activity 1 . Evidence shows that regulatory T cells (T reg ) are also involved in the progression to cervical neoplasia in HPV-infected patients [2][3][4][5] .…”

mentioning

confidence: 99%

Glucocorticoid-induced tumor necrosis factor receptor expression in patients with cervical human papillomavirus infection

Padovani

Bonin

Tozetti

et al. 2013

Rev. Soc. Bras. Med. Trop.

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ORIGINAL ARTICLE: Regulatory T Cells in a Spectrum of HPV‐Induced Cervical Lesions: Cervicitis, Cervical Intraepithelial Neoplasia and Squamous Cell Carcinoma

Abstract: Cervical tumors are marked by the presence of an immunoregulatory environment, and harbor equal proportions of 'inactive' n Tregs; activated n Tregs; and Tregs operating via TGFbeta. nTregs in cervicitis and CIN may be a potential marker of persistence.

Cited by 52 publications

References 37 publications

Location and Density of Immune Cells in Precursor Lesions and Cervical Cancer

Location and Density of Immune Cells in Precursor Lesions and Cervical Cancer

Effect of human papillomavirus infection on the immune system and its role in the course of cervical cancer

Glucocorticoid-induced tumor necrosis factor receptor expression in patients with cervical human papillomavirus infection

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