| 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]
Número total de Autores: 10
|
| 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
Número total de Afiliações: 5
|
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) |