Altered Treg and IL-1A Expression in the Immune Microenvironment of Lung Squamous-cell Cancer after EGFR Blockade
10.3779/j.issn.1009-3419.2017.03.01
- VernacularTitle:阻断EGFR影响肺鳞癌肿瘤微环境Treg细胞及IL-1A表达
- Author:
HE HAIYANG
1
;
QI LUYU
;
HOU YILING
Author Information
1. 武警后勤学院
- Keywords:
EGFR;
Lung neoplasms;
Gefitinib;
Tumor immune-environment;
T regulatory cells
- From:
Chinese Journal of Lung Cancer
2017;20(3):143-148
- CountryChina
- Language:Chinese
-
Abstract:
Background and objective Targeting the mutations and amplifications in the epidermal growth factor receptor (EGFR) gene has curative effects on cancers of the lung, oral cavity, and gastrointestinal system. However, a systemic immune inflammation is an adverse effect of this therapeutic strategy. In this study, we aimed to identify the possible changes in the tumor microenvironment that contribute to the anti-cancer activity of EGFR inhibition.Methods Squamous-cell cancers were induced by the syngeneic transplantation of either EGFR-null or wild-type mouse primary keratinocytes that had been transduced with an oncogenic H-ras retrovirus. The mice were treated with gefinitib. Then, flow cytometric was used to detect the ratio of T cells and the expression of programmed cell death receptor 1 (PD-1). RT-PCR was used to detect the expression of cytokines and chemokines.Results Tumors that formed from EGFR-null keratinocytes were smaller, had fewer infilltrat-ing FoxP3+ Treg cells, lower Foxp3 RNA, and lower percentage of PD-1 positive CD4 cells than those formed from wild-type keratinocytes. These results indicated that tumor cells can autonomously regulate the tumor microenvironment. Hosts with wild-type cancers and that were treated with gefitinib for 1 week tended to have smaller tumors. The treated mice in the short-term pharmacological model tended to have reduced FoxP3+ cells and FoxP3 RNA in the tumor microenvironment, as well as a substantially increased ratio of IL-1A/IL-1RA transcripts. These results suggested that the brief systemic inhibition of EGFR signaling alters the immune environment of the targeted cancer.Conclusion The autonomous (genetic) or systemic (pharmacologic) inhibition of EGFR signaling in tumor cells reduces tumor growth and Treg infilltration in the tumor micro-environment. An EGFR-dependent Treg function supports the growth of squamous cancers. Therefore, Treg is a target in the therapeutic strategy of EGFR inhibition.
