ILT4 drives B7-H3 expression via PI3K/AKT/mTOR signalling and ILT4/B7-H3 co-expression correlates with poor prognosis in non-small cell lung cancer

Pei Zhang; Shuwen Yu; Hongyu Li; Chuanyong Liu; Juan Li; Wenli Lin; Aiqin Gao; Linlin Wang; Wei Gao; Yuping Sun

doi:10.1016/j.febslet.2015.06.037

ILT4 drives B7-H3 expression via PI3K/AKT/mTOR signalling and ILT4/B7-H3 co-expression correlates with poor prognosis in non-small cell lung cancer

FEBS Lett. 2015 Aug 4;589(17):2248-56. doi: 10.1016/j.febslet.2015.06.037. Epub 2015 Jul 3.

Authors

Pei Zhang¹, Shuwen Yu², Hongyu Li³, Chuanyong Liu¹, Juan Li¹, Wenli Lin¹, Aiqin Gao¹, Linlin Wang¹, Wei Gao⁴, Yuping Sun⁵

Affiliations

¹ Department of Oncology, Jinan Central Hospital, Shandong University, 105 Jie Fang Road, Jinan, Shandong 250013, PR China.
² Department of Pharmacy, Jinan Central Hospital, Shandong University, 105 Jie Fang Road, Jinan, Shandong 250013, PR China.
³ Department of Geratology, Jinan Central Hospital, Shandong University, 105 Jie Fang Road, Jinan, Shandong 250013, PR China.
⁴ Department of Pathology, Jinan Central Hospital, Shandong University, 105 Jie Fang Road, Jinan, Shandong 250013, PR China.
⁵ Department of Oncology, Jinan Central Hospital, Shandong University, 105 Jie Fang Road, Jinan, Shandong 250013, PR China. Electronic address: 13370582181@163.com.

PMID: 26149216
DOI: 10.1016/j.febslet.2015.06.037

Abstract

Immunoglobulin-like transcript (ILT) 4 is critical for the inhibitory function of certain immune cells. We previously demonstrated that ILT4 is over-expressed in human non-small cell lung cancer (NSCLC) cells and is involved in tumour evasion via an unknown mechanism. In this report, we demonstrate that ILT4 increases the expression of the co-inhibitory molecule B7-H3 through PI3K/AKT/mTOR signalling. In primary human NSCLC tissues, a significant positive relationship is observed between ILT4 and B7-H3 expression. ILT4/B7-H3 co-expression is significantly associated with a reduction in T infiltrating lymphoid cells and lower overall survival. In summary, ILT4 increases B7-H3 expression and ILT4/B7-H3 co-expression may be involved in NSCLC progression.

Keywords: B7-H3; ILT4; Non-small cell lung cancer; PI3K/AKT/mTOR signalling.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

B7 Antigens / genetics*
B7 Antigens / metabolism
Blotting, Western
Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Non-Small-Cell Lung / metabolism
Carcinoma, Non-Small-Cell Lung / pathology
Cell Line, Tumor
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Lung Neoplasms / genetics*
Lung Neoplasms / metabolism
Lung Neoplasms / pathology
Male
Membrane Glycoproteins / genetics*
Membrane Glycoproteins / metabolism
Middle Aged
Phosphatidylinositol 3-Kinases / genetics*
Phosphatidylinositol 3-Kinases / metabolism
Prognosis
Proto-Oncogene Proteins c-akt / genetics*
Proto-Oncogene Proteins c-akt / metabolism
RNA Interference
Receptors, Immunologic / genetics*
Receptors, Immunologic / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / genetics
TOR Serine-Threonine Kinases / genetics*
TOR Serine-Threonine Kinases / metabolism

Substances

B7 Antigens
CD276 protein, human
LILRB2 protein, human
Membrane Glycoproteins
Receptors, Immunologic
MTOR protein, human
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases