Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Discussion session - Basic science

2122 - The role of EGFR inhibitor (EGFRi) in immune cell infiltration and CD8+ T-cell activation in EGFR mutant lung cancer

Date

29 Sep 2019

Session

Poster Discussion session - Basic science

Presenters

Fenge Li

Citation

Annals of Oncology (2019) 30 (suppl_5): v1-v24. 10.1093/annonc/mdz238

Authors

F. Li1, G. Lizee2, P. Hwu2, X. Du3, L. Deng4, A. Talukder1, A. Katailiha1, Q. Zou4, J. Roszik1, D. Hawke1, K. Jackson1, S. Bradley1, Y. Wang4, R. Ataullakhanov5, A. Bagaev5, N. Kotlov5, V. Svekolkin5, N. Miheecheva5, F. Frenkel5, H. Sonnemann1

Author affiliations

  • 1 Department Of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 2 Department Of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston/US
  • 3 Oncology Department, Tianjin Beichen Hospital, Tianjin/CN
  • 4 Research And Development Department, Tianjin HengJia Biotechnology Development Co., Ltd., Tianjin/CN
  • 5 Bostongene Corporation, BostonGene Corporation, Boston/US

Resources

Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 2122

Background

Oncogenic MAP kinase pathway activating mutations have been shown to drive immune suppression in melanoma and colorectal cancers. In this study, we explored whether oncogenic EGFR mutations play an analogous role in non-small cell lung cancer (NSCLC), and whether EGFRi can relieve tumor-associated immune suppression.

Methods

Lung cancer cell lines expressing wild-type or mutated EGFR were treated with EGFRi, followed by collection of RNA and cell supernatants. In parallel, tumor biopsies from NSCLC patients receiving a personalized peptide vaccine with or without concurrent EGFRi treatment were obtained. RNAseq-based transcriptome profiles of tumor cell lines and patient tumor biopsies were compared to assess common gene signatures driven by EGFRi. Gene expression changes were confirmed at the protein level using Western blot, flow cytometry, and cytokine/chemokine Luminex. The impact of EGFRi on T-cell migration and tumor cell recognition by antigen-specific CD8+ T cells was also assessed.

Results

In addition to downregulating genes associated with cell proliferation, apoptosis and survival, EGFRi increased the transcription of genes associated with TNFa and TRAIL signaling, and antigen presentation. HLA class I protein upregulation was confirmed and correlated with increased recognition of tumor cells by cytotoxic T cells. Several chemokines and cytokines were up- or down-regulated following EGFRi treatment, and Luminex analysis confirmed changes to 10 of them. Migration assays demonstrated that chemotaxis of T cells towards EGFR-mutant cell supernatants increased in an EGFRi dose-dependent manner. Transcriptome profiling of tumor biopsies revealed similar gene expression changes in on-EGFRi treatment tumor samples. Furthermore, increased tumor immune cell infiltration observed in EGFRi-treated patient tumors was consistent with the upregulation of EGFRi signature chemokines at the tumor site.

Conclusions

These results provide evidence that EGFRi has the capacity to facilitate modulation of the tumor microenvironment to favor immune cell infiltration and promote T-cell mediated antitumor immunity.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The University of Texas MD Anderson Cancer Center.

Funding

Tianjin HengJia Biotechnology Development Co., Ltd.

Disclosure

F. Li: Shareholder/Stockholder/Stock options: Tianjin HengJia Biotechnology Development Co., Ltd.. G. Lizee: Advisory/Consultancy: HengJia Neoantigen Biotechnology (Tianjin) Co., Ltd.. P. Hwu: Advisory/Consultancy: Dragonfly Therapeutics; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Immatics; Advisory / Consultancy: Sanofi; Research grant/Funding (institution): Genentech. L. Deng: Full/Part-time employment: Tianjin HengJia Biotechnology Development Co., Ltd.. Q. Zou: Full/Part-time employment: Tianjin HengJia Biotechnology Development Co., Ltd.. Y. Wang: Full/Part-time employment: Tianjin HengJia Biotechnology Development Co., Ltd.. R. Ataullakhanov: Full/Part-time employment: Bostongene. Llc. Bagaev: Full/Part-time employment: Bostongene. Llc. N. Kotlov: Full/Part-time employment: Bostongene. Llc. V. Svekolkin: Full/Part-time employment: Bostongene. Llc. N. Miheecheva: Full/Part-time employment: Bostongene. Llc. F. Frenkel: Full/Part-time employment: Bostongene. Llc. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.