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

Autor(es):Mostrar menos -

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN ONCOLOGY; v. 10, NOV 19 2020.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 14/19326-6 - Microambiente tumoral, inflamação e imunomodulação: possibilidades terapêuticas e marcadores de prognóstico
• Beneficiário: Ana Paula Lepique
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/26856-9 - Papel do metabolismo de tumores associados ao Papilomavírus humano na modulação do fenótipo de macrófagos humanos
• Beneficiário: Simone Cardozo Stone
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/16149-1 - Efeito do inibidor da alfa-manosidase, Swainsonina, sobre o fenótipo de macrófagos associados a tumores
• Beneficiário: Marcella Cipelli
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 18/16989-5 - O microambiente tumoral e a modulação da resposta de células mielóides.
• Beneficiário: Ana Paula Lepique
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/20499-4 - Caracterização do processo inflamatório em lesões do colo uterino associadas à infecção por papilomavírus humano
• Beneficiário: Karla Lucía Alvarez Fernández
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto