Interleukin-35 Suppresses the Antitumor Activity of T Cells in Patients with Non-Small Cell Lung Cancer.
Cell Physiol Biochem
; 47(6): 2407-2419, 2018.
Article
de En
| MEDLINE
| ID: mdl-29991058
ABSTRACT
BACKGROUND/AIMS:
Interleukin (IL)-35 has immunosuppressive functions in autoimmune diseases, infectious diseases, and certain cancers. However, few studies have focused on its immunoregulatory activity in non-small cell lung cancer (NSCLC). Thus, we investigated the role of IL-35 in the pathogenesis of this disease.METHODS:
A total of 66 NSCLC patients and 21 healthy individuals were enrolled. IL-35 expression in peripheral blood and bronchoalveolar lavage fluid (BALF) was measured. The modulatory functions of IL-35 on purified CD4+ and CD8+ T cells from NSCLC patients were investigated in direct and indirect coculture systems with NSCLC cell lines.RESULTS:
IL-35 expression was significantly increased in BALF from the tumor site, but not in the peripheral blood of NSCLC patients. IL-35 did not affect the bioactivity including proliferation, cytokine production, cell cycle, and cellular invasion of NSCLC cells. It suppressed responses from type 1 T helper (Th1) and Th17 cells but elevated the regulatory T cell response in cultured CD4+ T cells from NSCLC patients, and reduced cytokine-mediated CD4+ T cells cytotoxicity to NSCLC cells. Moreover, IL-35 also inhibited cytotoxic gene expression in CD8+ T cells from NSCLC, reducing their cytolytic and noncytolytic functions.CONCLUSION:
The results of this study suggest that IL-35 contributes to the dysfunction/exhaustion of T cells and limited antitumor immune responses in NSCLC.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Lymphocytes T CD4/
/
Régulation de l'expression des gènes tumoraux
/
Interleukines
/
Carcinome pulmonaire non à petites cellules
/
Lymphocytes T CD8/
/
Tumeurs du poumon
/
Protéines tumorales
Limites:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Langue:
En
Journal:
Cell Physiol Biochem
Sujet du journal:
BIOQUIMICA
/
FARMACOLOGIA
Année:
2018
Type de document:
Article
Pays d'affiliation:
Chine