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Evaluation of tumour associated Macrophages M1 and M2 in response to the anti-tumour C36L1 peptide

Grant number: 15/23898-8
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): July 04, 2016
Effective date (End): July 03, 2017
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Luiz Rodolpho Raja Gabaglia Travassos
Grantee:Carlos Rogerio de Figueiredo
Supervisor abroad: Ainhoa Mielgo Iza
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Local de pesquisa : University of Liverpool, England  
Associated to the scholarship:14/50723-1 - Mechanism of action of the do apeptide C36L1, a microtubule depolymerization agente, in the activation of dendritic and metastatic melanoma therapy , BP.PD

Abstract

The effective anti-cancer immune response involves several effector mechanisms involving antibodies, T lymphocytes, cytokines, macrophages and dendritic cells as central elements, associating tumor antigen recognition and anti-tumour immunity. Our laboratory, in collaboration with researchers from the University of Parma, Italy, showed that short peptide sequences from complementarity-determining regions (CDRs) of immunoglobulins exert anti-infective, immune-modulatory and anti-tumour activities, irrespective of the original antibody specificity. We have shown that the CDR synthetic peptide C36L1 displayed relevant anti-tumour effects against melanoma, both in vitro and in vivo. Intraperitoneal administration of C36L1 in a syngeneic metastatic melanoma model induced significant immune-protection, with increased tumour infiltrate of both CD4+ and CD8+ T cells, together with macrophages (F4/80+ CD40+). Monocytic cells may reach the tumor stroma,differentiate into macrophages and polarize into pro-inflammatory M1-like or immune-suppressive M2-like macrophages. Particularly, the M1 subtype has been shown to have a role in the eradication of large established melanomas and the M2 subtype is believed to elicit immune-suppressive effects. Therefore, understanding the phenotypic and functional profile of tumor infiltrated M1 and M2 macrophages in response to C36L1 peptide treatment of melanoma is of high relevance to the current project. This will allow us to identify key immune-modulatory mechanisms involved in the C36L1 induced anti-tumor activity.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FIGUEIREDO, CARLOS R.; AZEVEDO, RICARDO A.; MOUSDELL, SASHA; RESENDE-LARA, PEDRO T.; IRELAND, LUCY; SANTOS, ALMUDENA; GIROLA, NATALIA; CUNHA, RODRIGO L. O. R.; SCHMID, MICHAEL C.; POLONELLI, LUCIANO; TRAVASSOS, LUIZ R.; MIELGO, AINHOA. Blockade of MIF-CD74 Signalling on Macrophages and Dendritic Cells Restores the Antitumour Immune Response Against Metastatic Melanoma. FRONTIERS IN IMMUNOLOGY, v. 9, MAY 23 2018. Web of Science Citations: 5.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.