395O - Potential predictive value for adjuvant PD-1 blockade based on histologic subtype in resected lung adenocarcinoma

Date 19 December 2016
Event ESMO Asia 2016 Congress
Session Immunotherapy of cancer
Topics Non-small-cell lung cancer
Immunotherapy
Presenter Zhong-Yi Dong
Citation Annals of Oncology (2016) 27 (suppl_9): ix123-ix125. 10.1093/annonc/mdw588
Authors Z. Dong, W. Zhong, S. Liu, Z. Xie, S. Wu, Y. Wu
  • Guangdong Lung Cancer Institute, Guangdong General Hospital, 510080 - Guangzhou/CN

Abstract

Background

Only a minority of patients benefit from adjuvant chemotherapy in early stage non-small cell lung cancer (NSCLC) and merely with an increase of 4% at five years overall survival. Adjuvant immunotherapy including tumor vaccine and checkpoint blockade had been recently thought to be a promising strategy for postoperative NSCLC. This study was sought to identify the potential superior population of resected lung adenocarcinoma that will benefit most from adjuvant programmed cell death protein-1 (PD-1) blockade.

Methods

We performed an integrated analysis on the multiple-dimensional data types including genomic, transcriptomic, proteomic and clinical data from cohorts of both lung adenocarcinoma public database, such as The Cancer Genome Atlas (TCGA), and surgical patients in our center. Immunohistochemical (IHC) staining was carried out to analysis expression of PD-L1 and CD8.

Results

Solid predominant adenocarcinoma (SPA) showed remarkable increased expression of PD-L1 in both mRNA and protein levels. Furthermore, we confirmed the association of SPA subtype with elevated PD-L1 expression (P = 0.001) and enrichment of CD8+ tumor-infiltrating lymphocytes (TILs) (P = 0.022) in 124 lung adenocarcinoma surgical specimens using an IHC analysis. Specifically, SPA subtype significantly activated T-effector and IFN-γ associated gene signature compared with nonsolid subtype, indicating pre-existing immunity within this group. More importantly, we had identified there was a notable increase of nonsynonymous mutation in tumors with SPA subtype than other subtypes based on analysis of 377 resected lung adenocarcinoma samples from TCGA and Broad database. Meanwhile, we could also identify SPA subtype were significantly enriched in the transversion-high (TH) cohort based on TCGA, and these findings were also confirmed by Broad database that higher rate of transversion/transition in SPA subtype compared with other subtypes.

Conclusions

These findings provide the basis that SPA may be served as a potential superior group for adjuvant PD-1 blockade immunotherapy. Further investigation based on clinical trial of adjuvant PD-1 blockade in different histologic subtype of lung adenocarcinoma will be necessary in the future.

Clinical trial indentification

Legal entity responsible for the study

N/A

Funding

This study was supported by the Key Technologies Research and Development Program of Guangzhou (2011Y2-00014), the Key Laboratory Program of Guangdong (2012A061400006)

Disclosure

All authors have declared no conflicts of interest.