Neutrophils dominate the immune cell composition in non-small cell lung cancer

Julia Kargl,Stephanie E Busch,Kyoung-Hee Kim,Grace H Y Yang,A Mcgarry Houghton,Heather E Metz,Mark L Hanke,Jesse J Hubbard,Martin W Mcintosh,David K Madtes,Sylvia M Lee

doi:10.1038/ncomms14381

Abstract

The response rate to immune checkpoint inhibitor therapy for non-small-cell lung cancer (NSCLC) is just 20%. To improve this figure, several early phase clinical trials combining novel immunotherapeutics with immune checkpoint blockade have been initiated. Unfortunately, these trials have been designed without a strong foundational knowledge of the immune landscape present in NSCLC. Here, we use a flow cytometry panel capable of measuring 51 immune cell populations to comprehensively identify the immune cell composition and function in NSCLC. The results show that the immune cell composition is fundamentally different in lung adenocarcinoma as compared with lung squamous cell carcinoma, and that neutrophils are the most prevalent immune cell type. Using T-cell receptor-β sequencing and tumour reactivity assays, we predict that tumour reactive T cells are frequently present in NSCLC. These results should help to guide the design of clinical trials and the direction of future research in this area.

Highlights

The response rate to immune checkpoint inhibitor therapy for non-small-cell lung cancer (NSCLC) is just 20%
NSCLC is typically subdivided into lung adenocarcinoma (L-ADCA) and lung squamous cell carcinoma (L-SCCA), which account for B70% and B20% of NSCLC, respectively[8]
The malignant portion of NSCLC and many other solid tumour types have been comprehensively profiled at the molecular level, including mutational spectra[10,11,12]

Summary

Introduction

The response rate to immune checkpoint inhibitor therapy for non-small-cell lung cancer (NSCLC) is just 20%. To improve this figure, several early phase clinical trials combining novel immunotherapeutics with immune checkpoint blockade have been initiated. Several early phase clinical trials combining novel immunotherapeutics with immune checkpoint blockade have been initiated These trials have been designed without a strong foundational knowledge of the immune landscape present in NSCLC. Using T-cell receptor-b sequencing and tumour reactivity assays, we predict that tumour reactive T cells are frequently present in NSCLC These results should help to guide the design of clinical trials and the direction of future research in this area. Given the emergence of novel immunebased drugs, a strong foundational knowledge of the immune cell composition and function in NSCLC, and in other solid tumours as well, will likely prove prerequisite to realizing the full potential of such reagents

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Conclusion