Interaction of T-reg and NK lymphocytes from ovarian cancer patients during cytotoxic activity against ovarian neoplasia

• Grant number: 14/07401-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2014
• End date: February 28, 2018
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Sophie Françoise Mauricette Derchain
• Grantee: Rodrigo Fernandes da Silva
• Host Institution: Centro de Atenção Integral à Saúde da Mulher (CAISM). Hospital da Mulher Professor Doutor José Aristodemo Pinotti. Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 15/21979-0 - Understanding T regulatory cell mediated regulation of tumor fighting NK cells in a novel murine model of lung cancer, BE.EP.DR

Abstract

Natural Killer cells are cytotoxic lymphocytes that are part of the inate immune response against viral infections and neoplasia. Recently, we have demonstrated that it is possible to obtain preparations of effector cells rich in NK cells from patients with ovarian neoplasia, by long-term culture of peripheral blood mononuclear cells (PBMC) in vitro. The effector cells obtained have a significant greater proportion of functional NK cells than the usual LAK cells (lymphokine activated killer) preparations. Additionally we observed a significant increase in the expression of various activating receptors on NK cells, including the DNAM-1, which is often decreased on NK cells of patients with malignant ovarian neoplasia. Furthermore, preliminary data indicate that the expansion of effector cells from ovarian cancer patients usually expands regulatory T lymphocytes (T-reg), which modulates the function of NK cells. T-reg have been identified to play a role in mechanisms of immunosuppression against tumors, including ovarian cancer. In general, the presence of T-reg cells in tumor infiltrated lymphocytes and the production of the cytokines TGF-² and IL-10 are associated with worse prognosis. However, it is not known the specific mechanisms in which T-reg lymphocytes modulate the function of NK cells. Thus, this study aims to evaluate the interaction between NK and T-reg lymphocytes from ovarian cancer patients, to elucidate possible modulation mechanisms of the effector function of NK cells. (AU)

Scientific publications

(4)

(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)

CARDOZO, DANIELA MAIRA; MARANGON, AMANDA VANSAN; DA SILVA, RODRIGO FERNANDES; PENTEADO ARANHA, FRANCISCO JOSE; LAGUILA VISENTAINER, JEANE ELIETE; ALVES BONON, SANDRA HELENA; BOTELHO COSTA, SANDRA CECILIA; MARTINS MIRANDA, ELIANA CRISTINA; DE SOUZA, CARMINO ANTONIO; GUIMARAES, FERNANDO. Synergistic effect of KIR ligands missing and cytomegalovirus reactivation in improving outcomes of haematopoietic stem cell transplantation from HLA-matched sibling donor for treatment of myeloid malignancies. HUMAN IMMUNOLOGY, v. 77, n. 10, p. 861-868, OCT 2016. (14/07401-3, 13/12625-5)

DA SILVA, RODRIGO FERNANDES; YOSHIDA, ADRIANA; CARDOZO, DANIELA MAIRA; JALES, RODRIGO MENEZES; PAUST, SILKE; DERCHAIN, SOPHIE; GUIMARAES, FERNANDO. Natural Killer Cells Response to IL-2 Stimulation Is Distinct between Ascites with the Presence or Absence of Malignant Cells in Ovarian Cancer Patients. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 18, n. 5, MAY 2017. (14/07401-3)

DA SILVA, RODRIGO FERNANDES; CARDOZO, DANIELA MAIRA; LIBANIO RODRIGUES, GISELE OLINTO; DE SOUZA-ARAUJO, CAROLINE NATANIA; MIGITA, NATACHA AZUSSA; LUCCI DE ANGELO ANDRADE, LILIANA APARECIDA; DERCHAIN, SOPHIE; YUNES, JOSE ANDRES; GUIMARAES, FERNANDO. CAISMOV24, a new human low-grade serous ovarian carcinoma cell line. BMC CANCER, v. 17, NOV 13 2017. (11/14520-0, 16/07822-4, 14/07401-3, 12/12802-1)

DA SILVA, RODRIGO FERNANDES; YOSHIDA, ADRIANA; CARDOZO, DANIELA MAIRA; JALES, RODRIGO MENEZES; PAUST, SILKE; DERCHAIN, SOPHIE; GUIMARAES, FERNANDO. Natural Killer Cells Response to IL-2 Stimulation Is Distinct between Ascites with the Presence or Absence of Malignant Cells in Ovarian Cancer Patients. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 18, n. 5, p. 15-pg., 2017-05-01. (14/07401-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVA, Rodrigo Fernandes da. Characterization of the tumor microenvironment of ovarian cancer patients in relation to lymphocytes subtypes, cytokines and functional activation of natural killer cells. 2018. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.