1920 - Differential expression of B7-H4, VISTA, B7-H6, HHLA2, IDO-1, PD-L1 and CD8 in EGFR mutant and wild-type lung adenocarcinoma

Background

The aim of this study was to describe the expression profiles of newly discovered B7 family (B7-H4, VISTA, B7-H6, HHLA2), IDO-1, PD-L1 and CD8 in resected lung adenocarcinoma tumor tissues and try to find potential immune target for lung cancer with EGFR mutation.

Methods

A total of 372 adenocarcinoma lung cancer patients who underwent lung cancer resection were selected in the discovery cohort. The validation cohort contains another 231 adenocarcinoma lung cancer patients. Expression of B7-H4, VISTA, B7-H6, HHLA2, IDO-1, PD-L1 and CD8 was determined by immunohistochemical staining.

Results

In the discovery cohort, 44.9% (167/372) of B7H4, 75.8% (282/372) of VISTA, 84.7% (315/372) of B7H6, 61.0% (227/372) of IDO-1 was positively stained in lung adenocarcinoma tissues. In the validation cohort, majority of cases was positive for B7H4 (41.6%, 96/231), VISTA (74.5%, 172/231), B7H6 (86.4%, 200/231) and IDO-1 (57.1%, 132/231), which was similar to the initial cohort. The positive expression rate of B7H4 in EGFR mutation group was significantly higher than that in wild type group in both cohort (P < 0.05). However, expressions of IDO-1, PD-L1 and CD8 in wild type group were significantly higher than that in mutation group in discovery cohort, which was confirmed in the validation cohort. In the discovery cohort, the median IHC scores of B7H4 and HHLA2 for the EGFR mutation group were significantly higher than those in wild type group (P = 0.045 for B7H4; P = 0.003 for HHLA2). Whereas the median IHC scores of IDO-1 and PD-L1 in wild type group were significantly higher than those in mutation group (P = 0.000 for IDO-1; P = 0.000 for PD-L1). Results in the validation cohort confirmed observation above. In both discovery and validation set, the co-expressions of B7-H6, IDO-1, PD-L1 and CD8 were significantly higher in EGFR wild type group than those in EGFR mutation group.

Conclusions

Aberrant expressions of B7-H4 and HHLA2 were more obvious in EGFR mutation lung cancer. High co-expression of CD8 and IDO-1 in EGFR wild type patients reveals a potential good clinical efficacy of anti-IDO-1 therapy in patients with EGFR wild type.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Jifeng Feng.

Funding

The National Natural Science Foundation of China.

Disclosure

All authors have declared no conflicts of interest.