NK cells and the profile of inflammatory cytokines in the peripheral blood of patients with advanced carcinomas

• Ano de defesa: 2021
• Autor(a) principal: Saito, Luciana Mieli
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Biblioteca Digitais de Teses e Dissertações da USP
• Palavras-chave em Português: Advanced solid tumors; Carcinoma; Células natural killer; Chemokines; Citocinas; Coleta de amostras de sangue; Cytokines; Fatores de crescimento; Growth factors; Natural killer cells; Peripheral blood; Quimiocinas
• Link de acesso: https://www.teses.usp.br/teses/disponiveis/25/25149/tde-29112021-121951/

Cancer is a multifactorial disease caused by a series of mutagenic alterations in genome which allow cancer cells to evade from immune surveillance, contributing to tumor progression. One of the most crucial immune cells that mediate the antitumoral response due to their ability to immediately recognize and eliminate transformed cells are the natural killer (NK) cells. These cells can be modulated by cancer and other immune cells in tumor microenvironment though different cytokines production. Indeed, currently studies have been investigated this regulation for cancer immunotherapy. Here, we aimed to identify the cytokine levels in peripheral blood (PB) of advanced carcinoma patients related to NK cells subtypes, according to the perspective of tumor infiltrating immune cells. The study included 18 patients with advanced cancer during or after to treatment and 10 healthy donors. The frequency and the expression of activating (NKp46) and inhibitory (CD158b) molecules of CD56brightCD16- and CD56dimCD16+ NK cells were assessed by flow cytometry and the multiplex Luminex platform was used to quantify the secreted factors presented in the serum. Cancer patients had a lower frequency of the cytotoxic CD56dimCD16+ NK cells subtset in comparison with healthy controls. Also, the regulatory CD56brightCD16- NKs isolated from cancer patients exhibited a significantly lower expression of NKp46. The chemokines MCP-1, IP10, and eotaxin and the growth factor VEGF were the most prominent secreted factors detected in cancer patient´s blood. The correlation test showed that IL-12p40 is positively correlated with CD56brightCD16- NK cells. We also observed a positive correlation between MCP-1 and the activating marker NKp46 and a negative correlation between IP-10 and TNF- and NKp46. CD158b expression in CD56dimCD16+ was positively correlated with EGF and negatively correlated with MIP-1.