98O - Characterization of tumor infiltrating lymphocytes in resectable early stage non-small cell lung cancer

Date 14 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Multidisciplinary management of thoracic malignancies
Topics Non-Small Cell Lung Cancer
Pathology/Molecular Biology
Translational Research
Basic Scientific Principles
Basic Principles in the Management and Treatment (of cancer)
Presenter Sean Hall
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors S.R.R. Hall1, L. Wang1, T.M. Marti1, R. Peng2, L. Froment2, S. Berezowska3, G. Kocher1, P. Dorn2, R.A. Schmid2
  • 1Division Of General Thoracic Surgery, Inselspital Bern, 3010 - Bern/CH
  • 2Division Of General Thoracic Surgery, Inselspital Bern, Bern/CH
  • 3Experimental And Clinical Pathology, Institute Of Pathology, University of Bern, 3010 - Bern/CH

Abstract

Background

Blockade of the Programmed Cell Death 1: Programmed Cell Death ligand 1 (PD-1:PD-L1) pathway has shown durable antitumor responses in non-small cell lung cancer (NSCLC). Despite this initial success, the majority of patients with documented PD-L1 expression fail to respond. However, the immunophenotype and underlying alterations in tumor infiltrating T cells in early stage NSCLC remains unexplored.

Methods

We analyzed the quantity and functional orientation of tumor infiltrating lymphocytes (TILs) from a cohort of NSCLC patients (n = 66) using a multiparameter flow cytometric approach. Tumor and matched normal samples resected from patients with histologically confirmed adenocarcinoma and squamous cell carcinoma were digested to single cell suspensions and examined for the simultaneous expression of a panel of fluorescently conjugated monoclonal antibodies directed at the following epitpoes: CD19, CD45RO, CD3, CD4, CD8, CD107a, PD-1 and CD127.

Results

In adenocarcinoma samples (n = 33), there was an enhanced infiltration of CD4+ T cells (p = 0.026) together with a decrease in tumor infiltrating CD8+ T cells (p = 0.06) in the tumor compartment when compared to matched uninvolved tissue, which was not found in squamous cell carcinoma (n = 33). Regardless of tumor histology, however, we found a significant reduction in cytotoxic degranulating CD4+ and CD8+ TILs based on a CD107ahiPD1lo phenotype in the tumor compartment, as the majority of TILs were CD107aloPD1hi (p 

Conclusions

Our observations show evidence of T cell exhaustion in resectable early stage NSCLC. Further study is required to determine the functional significance on tumor specific T cell immunity and whether this contributes, in part, to the evolving cancer immune escape mechanisms evident in late stage NSCLC via PD-1/PD-L1 pathway.

Clinical trial identification

Legal entity responsible for the study

Sean R.R. Hall and Ralph A. Schmid

Funding

Inselspital, Division of Thoracic Surgery

Disclosure

All authors have declared no conflicts of interest.