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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.)

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

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Author(s):
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]
Total Authors: 10
Affiliation:
[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
Total Affiliations: 5
Document type: Journal article
Source: PLoS One; v. 13, n. 7 JUL 5 2018.
Web of Science Citations: 5
Abstract

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)

FAPESP's process: 11/11121-8 - Study of signaling pathways triggered by and biological effects of CD40 in cervical tumors.
Grantee:Renata Ariza Marques Rossetti
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 14/19326-6 - Tumor microenvironment, inflammation and immunomodulation: therapeutic possibilities and prognostic markers
Grantee:Ana Paula Lepique
Support type: Regular Research Grants
FAPESP's process: 10/20010-2 - Immune response modulation by tumor cells
Grantee:Ana Paula Lepique
Support type: Regular Research Grants