Critical analysis of the prognostic role of tumor infiltrating lymphocytes in differentiated thyroid carcinomas

• Grant number: 11/19681-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): June 01, 2012
• Effective date (End): January 31, 2015
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Laura Sterian
• Grantee: Lucas Leite Cunha
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

This project is a sequence of my investigations during the previous Master project (process Fapesp nº 2009/10722-8) that will be finished at 02/10/2012. In these previous studies, we showed that concurrent chronic lymphocytic thyroiditis (CLT) is associated to increased relapse-free time of differentiated thyroid carcinoma (DTC) patients. Tumor infiltrating macrophages is associated to increased relapse-free time. Infiltration of CD3+ lymphocytes is associated to presence of metastasis at diagnosis whereas CD4+ and CD20+ lymphocytes are associated to good prognosis features. Infiltration of CD8+ lymphocytes was a prognositic marker of good outcome as well as CD56, but not B7H1. Infiltration of FoxP3+ lymphocytes (regulatory T lymphocytes) correlated with less aggressive features as smaller tumors and absence of extrathyroidal invasion. Likewise, infiltration of CD4+/IL17+ lymphocytes (Th17) is associated to absence of extrathyroidal invasion, suggesting that these cells may exert a protective role on DTC (submitted paper). Immune cells infiltration on DTC correlated to immunohistochemical profile of tumors, suggesting that tumor microenvironment is critical for modulation of antitumor immune response. In fact, tumors with B7H1 expression also present infiltration of Treg and macrophages. Older patients as well as advanced stages patients present higher B7H1 mRNA expression, suggesting that expression of this co-inhibitory molecule is associated to poor prognosis on DTC patients. The aim of present PhD project is to investigate the protein expression profile of benign and malign thyroid tumors in order to characterize presence of NK and memory T cells infiltration; access functionality of tumor infiltrating lymphocytes; and tumoral microenvironment. Our hypothesis is that infiltration of NK and memory T cells, as well as infiltration of activated lymphocytes, acting in a supposed proinflammatory microenvironment, can favor antitumor immune response, implying into a better outcome of DTC patients. A better understanding on antitumor immune response mechanisms may lead to new diagnostic and therapeutic methods. (AU)

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)

CUNHA, LUCAS LEITE; MARCELLO, MARJORY ALANA; MORARI, ELAINE CRISTINA; NONOGAKI, SUELY; CONTE, FABIO FRANGIOTTI; GERHARD, RENE; SOARES, FERNANDO AUGUSTO; VASSALLO, JOSE; WARD, LAURA STERIAN. Differentiated thyroid carcinomas may elude the immune system by B7H1 upregulation. Endocrine-Related Cancer, v. 20, n. 1, p. 103-110, FEB 2013. (11/19681-2)