Anti-EGFR mAb cetuximab therapy increases T cell receptor (TCR) diversity in the peripheral blood and focuses TCR richness in the tumor microenvironment

Benjamin A Kansy,Yan Lin,Hyun-Bae Jie,Robert L Ferris,Sandra Poveda Gibson,Fei Ding

doi:10.1186/2051-1426-3-s2-p73

Abstract

T cell receptor (TCR) recognition of tumor antigen is essential for effective antitumor immunity. The immune system`s ability to respond to a broad spectrum of antigens requires a sophisticated selection of various TCR. So far, little is known about the role of TCR richness and clonality in the immune response to the EGFR-specific mAb, cetuximab. Therefore, we investigated differences in TCR sequences between HPV+ and HPV- patients, as well as differences in sequence characteristics between T cells of peripheral blood mononuclear cells (PBMC) and tumor infiltrating lymphocytes (TIL). Additionally, we were able to investigate the TCR richness and clonality in samples pre- and post-treatment in a clinical single agent cetuximab trial.

Highlights

T cell receptor (TCR) recognition of tumor antigen is essential for effective antitumor immunity
Using a cohort of neoadjuvant, single-agent cetuximab treated HNSCC patients, 56 samples were analyzed for global TCR diversity
Cetuximab therapy significantly increased the richness of unique sequences in peripheral blood mononuclear cells (PBMC) (p=0.0002)

Summary

Introduction

T cell receptor (TCR) recognition of tumor antigen is essential for effective antitumor immunity. The immune systems ability to respond to a broad spectrum of antigens requires a sophisticated selection of various TCR. Little is known about the role of TCR richness and clonality in the immune response to the EGFR-specific mAb, cetuximab. We investigated differences in TCR sequences between HPV+ and HPV- patients, as well as differences in sequence characteristics between T cells of peripheral blood mononuclear cells (PBMC) and tumor infiltrating lymphocytes (TIL). We were able to investigate the TCR richness and clonality in samples pre- and post-treatment in a clinical single agent cetuximab trial

Methods

Results

Conclusion