30P - Divergent PD-1 Expression in Tissue and Circulating CD8 Lymphocytes Defines an Immune Profile Predictive of the Response to Nivolumab in Advanced N...

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Complications of Treatment
Palliative and Supportive Care
Presenter Giulia Mazzaschi
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors G. Mazzaschi1, D. Madeddu1, M. Veneziani1, F. Sogni1, G. Armani1, C. Frati1, C. Lagrasta1, A. Falco1, B. Lorusso1, R. Vilella1, C. Mangiaracina1, G. Bocchialini1, E.M. Silini1, F. Facchinetti2, A. Ardizzoni3, G. Missale1, M. Tiseo2, F. Quaini1
  • 1Medicine And Surgery, University Hospital of Parma, 43126 - Parma/IT
  • 2Medical Oncology, Azienda Ospedaliera di Parma, 43126 - Parma/IT
  • 3Medical Oncology, Policlinico S. Orsola-Malpighi, 40138 - Bologna/IT

Abstract

Background

To predict the response to immunotherapy, tissue and circulating cytotoxic lymphocytes, potentially targeted by anti-PD-1/PD-L1 drugs, were simultaneously assessed in NSCLC.

Methods

Twenty-six advanced NSCLC patients receiving nivolumab were included. Tissue samples were immunohistochemically analyzed to quantify PD‐L1 (H‐score) and CD3, CD8, CD4 and PD-1 positive TILs. Peripheral blood (PB) immune profile at baseline (T0) and after 2 (T1) and 4 (T2) cycles of bi-weekly nivolumab was performed by FACS analysis of CD3, CD8, CD4, NK (CD56), Treg (FOXP3) and MDSC. Changes in their number, and functional (PD-1, Granzyme B, Perforin) and proliferative (Ki67) hallmarks were determined. Integrated tissue and circulating parameters were correlated to treatment response (RECIST 1.1).

Results

At tissue level, in association with variable PD-L1 degrees, low PD-1 expression in CD8pos TILs was present in 100% of patients with clinical benefit (CB, n 9) compared to only 20% of non-responders (NR, p 

Conclusions

The inhibitory and activating PD-1 pathways, respectively translated in low tissue PD-1posCD8pos TILs, to escape PD-L1 pressure and high peripheral blood PD-1posCD8pos, rescued by PD-1 targeting, may identify a specific immune profile predictive of the response to immunotherapy.

Clinical trial identification

Legal entity responsible for the study

University Hospital of Parma

Funding

AIRC project grant

Disclosure

All authors have declared no conflicts of interest.