B lymphocytes can be activated to act as antigen presenting cells to promote anti-tumor responses

Autor(es)

Marques Rossetti, Renata Ariza ^[1] ; Cristina Lorenzi, Noely Paula ^[2] ; Yokochi, Kaori ^[2] ; Sartor de Faria Rosa, Maria Beatriz ^[3] ; Benevides, Luciana ^[4] ; Ramos Margarido, Paulo Francisco ^[2] ; Baracat, Edmund Chada ^{[3, 2]} ; Carvalho, Jesus Paula ^[3] ; Villa, Luisa Lina ^{[3, 5]} ; 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, Hosp Univ, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Immunol & Biochem, Ribeirao Preto - Brazil

^[5] Univ Sao Paulo, Fac Med, Inst Radiol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 13, n. 7 JUL 5 2018.
• Citações Web of Science: 5

Resumo

Immune evasion by tumors includes several different mechanisms, including the inefficiency of antigen presenting cells (APCs) to trigger anti-tumor T cell responses. B lymphocytes may display a pro-tumoral role but can also be modulated to function as antigen presenting cells to T lymphocytes, capable of triggering anti-cancer immune responses. While dendritic cells, DCs, are the best APC population to activate naive T cells, DCs or their precursors, monocytes, are frequently modulated by tumors, displaying a tolerogenic phenotype in cancer patients. In patients with cervical cancer, we observed that monocyte derived DCs are tolerogenic, inhibiting allogeneic T cell activation compared to the same population obtained from patients with precursor lesions or cervicitis. In this work, we show that B lymphocytes from cervical cancer patients respond to treatment with sCD40L and IL-4 by increasing the CD80(+)CD86(+) population, therefore potentially increasing their ability to activate T cells. To test if B lymphocytes could actually trigger anti-tumor T cell responses, we designed an experimental model where we harvested T and B lymphocytes, or dendritic cells, from tumor bearing donors, and after APC stimulation, transplanted them, together with T cells into RAG1(-/-) recipients, previously injected with tumor cells. We were able to show that anti-CD40 activated B lymphocytes could trigger secondary T cell responses, dependent on MHC-II expression. Moreover, we showed that dendritic cells were resistant to the anti-CD40 treatment and unable to stimulate anti-tumor responses. In summary, our results suggest that B lymphocytes may be used as a tool for immunotherapy against cancer. (AU)

• Processo FAPESP: 11/11121-8 - Estudo das vias de sinalização disparadas por CD40 em tumores do colo uterino e seus efeitos biológicos
• Beneficiário: Renata Ariza Marques Rossetti
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 04/00749-2 - Interação entre HPV e o sistema imunológico em camundongos RAG-/- reconstituídos com células hematopoiéticas selvagens
• Beneficiário: Ana Paula Lepique
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• 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: 10/20010-2 - Modulação da resposta imune por células tumorais
• Beneficiário: Ana Paula Lepique
• Modalidade de apoio: Auxílio à Pesquisa - Regular