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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Local and Systemic STAT3 and p65 NF-KappaB Expression as Progression Markers and Functional Targets for Patients With Cervical Cancer

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Rossetti, Renata A. M. [1, 2] ; da Silva-Junior, Ildefonso A. [1] ; R Rodriguez, Gretel [1] ; Alvarez, Karla L. F. [1] ; Stone, Simone C. [1] ; Cipelli, Marcella [1] ; Silveira, Caio R. F. [1] ; Beldi, Mariana Carmezim [1] ; Mota, Giana R. [2] ; Margarido, Paulo F. R. [3] ; Baracat, Edmund C. [3] ; Uno, Miyuki [4] ; Villa, Luisa L. [2] ; Carvalho, Jesus P. [5] ; Yokochi, Kaori [2] ; Rosa, Maria Beatriz S. F. [5] ; Lorenzi, Noely P. [2] ; Lepique, Ana Paula [1]
Total Authors: 18
Affiliation:
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Immunol, Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Canc Estado Sao Paulo, Dept Radiol & Oncol, Fac Med, Sao Paulo - Brazil
[3] Univ Sao Paulo, Hosp Univ, Sao Paulo - Brazil
[4] Univ Sao Paulo, Biobanco Rede Acad Pesquisa Canc, Sao Paulo - Brazil
[5] Inst Canc Estado Sao Paulo, Ctr Translat Res Oncol, Sao Paulo - Brazil
Total Affiliations: 5
Document type: Journal article
Source: FRONTIERS IN ONCOLOGY; v. 10, NOV 19 2020.
Web of Science Citations: 0
Abstract

Cervical cancer, which main etiologic factor is Human Papillomavirus (HPV) infection, continues to be a burden for public health systems in developing countries. Our laboratory has been working with the hypothesis that signals generated in the tumor microenvironment can modulate local and systemic immune responses. In this context, it would be reasonable to think that tumors create pro-tumoral bias in immune cells, even before they are recruited to the tumor microenvironment. To understand if and how signaling started in the tumor microenvironment can influence cells within the tumor and systemically, we investigated the expression of key proteins in signaling pathways important for cell proliferation, viability, immune responses and tolerance. Besides, we used detection of specific phosphorylated residues, which are indicative of activation for Akt, CREB, p65 NF kappa B, and STAT3. Our findings included the observation of a significant STAT3 expression increase and p65 NF kappa B decrease in circulating leukocytes in correlation with lesion grade. In light of those observations, we started investigating the result of the inhibition of STAT3 in a tumor experimental model. STAT3 inhibition impaired tumor growth, increased anti-tumor T cell responses and decreased the accumulation of myeloid cells in the spleen. The concomitant inhibition of NF kappa B partially reversed these effects. This study indicates that STAT3 and NF kappa B are involved in immunomodulatory tumor effects and STAT3 inhibition could be considered as therapy for patients with cervical cancer. (AU)

FAPESP's process: 14/19326-6 - Tumor microenvironment, inflammation and immunomodulation: therapeutic possibilities and prognostic markers
Grantee:Ana Paula Lepique
Support Opportunities: Regular Research Grants
FAPESP's process: 13/26856-9 - Role of HPV associated tumor metabolism on human macrophage phenotype
Grantee:Simone Cardozo Stone
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 16/16149-1 - Alfa-mannosidase inhibitor effect, Swainsonina, on the phenotype of tumor associated macrophages
Grantee:Marcella Cipelli
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 18/16989-5 - The effect of the tumor microenvironment on myeloid cells.
Grantee:Ana Paula Lepique
Support Opportunities: Regular Research Grants
FAPESP's process: 11/20499-4 - Characterization of the inflammatory responses in human papillomavirus associated cervical lesions
Grantee:Karla Lucía Alvarez Fernández
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)