16P - A high-throughput RNAi screen for detection of immune-checkpoint molecules that mediated to cytotoxic T lymphocytes in lung cancer

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Cancer biology
Immunotherapy
Basic Scientific Principles
Therapy
Presenter Mian Xie
Citation Annals of Oncology (2016) 27 (6): 1-14. 10.1093/annonc/mdw362
Authors M. Xie1, Y. Gu2
  • 1Medical Oncology, The First Affiliated Hospital of Guangzhou Medical University, 510120 - Guangzhou/CN
  • 2Pathology, The First Affiliated Hospital of Guangzhou Medical University, 510120 - Guangzhou/CN

Abstract

Background

The success of T cell-based cancer immunotherapy is limited by tumor's resistance against killing by cytotoxic T lymphocytes (CTLs). Tumor-immune resistance is mediated by cell surface ligands that engage immune-inhibitory receptors on T cells. These ligands represent potent targets for therapeutic inhibition. So far, only few immune-suppressive ligands have been identified.

Methods

We here describe a rapid high-throughput siRNA-based screening approach that allows a comprehensive identification of ligands on lung cancer cells that inhibit CTL-mediated tumor cell killing.

Results

We demonstrate that IL6 exerts strong immune-regulatory effects on T cell responses in lung cancer. Unlike PDL1, which inhibits TCR signaling, IL6 regulates STAT3 in T cells, resulting in reduced T-helper-1 cytokine secretion and reduced cytotoxic capacity. Moreover, inhibition of IL6 expression on tumor cells facilitated immunotherapy of lung cancer by tumor-specific T cells in vivo.

Conclusions

Taken together, this method allows a rapid and comprehensive determination of immune-modulatory genes in lung tumor which represent the 'immune modulatome' of lung cancer.

Clinical trial identification

NO

Legal entity responsible for the study

N/A

Funding

Open Fund of State Key Laboratory of Southern China Oncology

Disclosure

All authors have declared no conflicts of interest.