Helper T Lymphocyte Response in the Peripheral Blood of Patients with Intraepithelial Neoplasia Submitted to Immunotherapy with Pegylated Interferon-α

Michelin, Márcia Antoniazi; Montes, Leticia Nunes; Nomelini, Rosekeila Simões; Trovó, Marco Aurélio; Murta, Eddie Fernando Cândido

doi:10.3390/ijms16035497

Cited by 6 publications

(7 citation statements)

References 23 publications

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“…8-9 Similarly to hepatitis C, higher levels of inflammatory modulators such as IL-4, IL-10, and TGF-beta, as well as an increase in lymphocytes expressing T regulatory cell marker FOXP3, were all associated with poorer treatment outcomes. 4,5,9 As such, it may be true that tumor regression in OSSN depends on a certain immunity profile.…”

Section: Discussionmentioning

confidence: 99%

Immunosuppression as a Possible Risk Factor for Interferon Nonresponse in Ocular Surface Squamous Neoplasia

Ashkenazy

Karp

Wang

et al. 2017

Cornea

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Purpose The mechanism by which ocular surface squamous neoplasia (OSSN) responds to topical interferon-alpha-2b (IFNα2b) is not known. We herein report on 3 cases of immunosuppressed patients whose tumors did not respond to topical IFNα2b therapy. The purpose of this series is to shed light on potential mechanisms of IFNα2b in OSSN. Methods Retrospective case series of 3 immunosuppressed patients whose biopsy proven OSSN did not respond to topical IFNα2b treatment. Results Three white, immunosuppressed males (mean age 70 years, range 66-76) were diagnosed with OSSN. Topical IFNα2b 1 million units/ml was started four times a day and utilized for a mean of 5 months (range 2-7 months) without adequate response. All patients were then switched to 5-fluorouracil (5-FU). Successful eradication of OSSN was achieved in two cases, and improvement of OSSN in another. The latter patient was switched to mitomycin C (MMC) with subsequent resolution of OSSN. Conclusion These cases suggest that an intact immune system may be an important link between IFNα2b therapy and tumor resolution. As such, topical IFNα2b may not be an optimal choice in patients with underlying immunosuppression. It may be more effective in this patient population to switch to a non-immune modulating therapy such as 5-FU or MMC.

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Section: Discussionmentioning

confidence: 99%

Immunosuppression as a Possible Risk Factor for Interferon Nonresponse in Ocular Surface Squamous Neoplasia

Ashkenazy

Karp

Wang

et al. 2017

Cornea

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“…However, our group demonstrated in previous studies [26,27,30] that some patients with cervical intraepithelial neoplasia (CIN) respond to immunotherapy while others did not. Thus, it would be imperative to understand the local and systemic mechanisms of the performance of these cytokines in the regression of these neoplasms.…”

Section: Introductionmentioning

confidence: 91%

“…This immunotherapy stimulates cell-mediated immune response that are essential to the elimination of HPV [25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Pegylated-interferon-alpha treatment modifying T cell cytokine proﬁle in tumor microenvironment of patients with cervical intraepithelial neoplasia

2021

EJGO

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The goal of the investigation was to compare the profiles the cytokines IL-2, IL-12, IFN-γ, TNF-α , TGF-β, IL-4, IL-6 in the endocervical and serum secretions of patients with cervical intraepithelial neoplasia (CIN) who had good or poor response to immunotherapy with pegylated (PEG)-Interferon-alpha. Methods: The study was performed with 16 patients who had been diagnosed with CIN II and III. Each patient was submitted to six injections of PEG-Interferon-α -2b subcutaneously. A ter each injection, endocervical secretion and serum samples were collected for cytokine levels by ELISA. Results: Of the 16 women, 43.75% (n = 7) showed good clinical response and lesion regression a ter treatment as seen by histopathological analysis. When we analyzed the pre-therapy, locally we observed a higher concentration of IL-4 in patients who did not respond to treatment (P = 0.0229). A ter treatment, there was a significant reduction in IL-4 in unresponsive patients (P = 0.0304). Patients responsive to IFN-α had a reduction in the concentrations the TNF-α a ter treatment (P = 0.0313). Conclusion: Immunotherapy with PEG-Interferon-α can reduce the damage caused by HPV by decreasing local in lammation by reducing the cytokines IL-4 and TNF-alpha during treatment in endocervical secretion. It seems that the regression is related to the immunological profile, mainly local, before treatment, as in the case of IL-4 and TNF-alpha, promoting a Th2 profile in those patients with therapeutic failure.

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“…Promising results have been achieved with IFN treatment in association with a vaccination against HPV16, consisting of E6-E7 synthetic peptides [93, 94]. IFNs are also capable of inducing apoptosis of infected cells and stimulating an antiviral state in healthy cells [95].…”

Section: Immune Modulation By E5 Oncoproteinmentioning

confidence: 99%

“…The powerful anti-viral and anti-tumor effects of IFNs have been evaluated in several clinical studies assessing their efficacy as therapy for autoimmune diseases [ 92 ], viral infection, and cervical cancer. Promising results have been achieved with IFN treatment in association with a vaccination against HPV16, consisting of E6-E7 synthetic peptides [ 93 , 94 ]. IFNs are also capable of inducing apoptosis of infected cells and stimulating an antiviral state in healthy cells [ 95 ].…”

Section: Immune Modulation By E5 Oncoproteinmentioning

confidence: 99%

hrHPV E5 oncoprotein: immune evasion and related immunotherapies

Freitas

Oliveira

Júnior

et al. 2017

J Exp Clin Cancer Res

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The immune response is a key factor in the fight against HPV infection and related cancers, and thus, HPV is able to promote immune evasion through the expression of oncogenes. In particular, the E5 oncogene is responsible for modulation of several immune mechanisms, including antigen presentation and inflammatory pathways. Moreover, E5 was suggested as a promising therapeutic target, since there is still no effective medical therapy for the treatment of HPV-related pre-neoplasia and cancer. Indeed, several studies have shown good prospective for E5 immunotherapy, suggesting that it could be applied for the treatment of pre-cancerous lesions. Thus, insofar as the majority of cervical, oropharyngeal and anal cancers are caused by high-risk HPV (hrHPV), mainly by HPV16, the aim of this review is to discuss the immune pathways interfered by E5 oncoprotein of hrHPV highlighting the various aspects of the potential immunotherapeutic approaches.

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Helper T Lymphocyte Response in the Peripheral Blood of Patients with Intraepithelial Neoplasia Submitted to Immunotherapy with Pegylated Interferon-α

Cited by 6 publications

References 23 publications

Immunosuppression as a Possible Risk Factor for Interferon Nonresponse in Ocular Surface Squamous Neoplasia

Immunosuppression as a Possible Risk Factor for Interferon Nonresponse in Ocular Surface Squamous Neoplasia

Pegylated-interferon-alpha treatment modifying T cell cytokine proﬁle in tumor microenvironment of patients with cervical intraepithelial neoplasia

hrHPV E5 oncoprotein: immune evasion and related immunotherapies

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