2O - Favorable clinical outcome and response to immunotherapy share a common PD-L1/PD-1 based NSCLC immune contexture

Date 06 May 2017
Event ELCC 2017
Session Immunotherapies and targeted therapies in advanced NSCLC
Presenter Giulia Mazzaschi
Citation Annals of Oncology (2017) 28 (suppl_2): ii1-ii5. 10.1093/annonc/mdx090
Authors G. Mazzaschi1, D. Madeddu1, G. Bocchialini1, L. Gnetti1, G. Armani1, F. Sogni1, M. Tiseo2, A. Ardizzoni3, F. Aversa1, F. Quaini1
  • 1Medicine, University Hospital of Parma, 43126 - Parma/IT
  • 2Medical Oncology Unit, University Hospital of Parma, 41100 - Parma/IT
  • 3University Hospital, Bologna/IT

Abstract

Background

The success of PD-1/PD-L1 immune checkpoint inhibitors strengthens the notion that tumor growth and regression are immune regulated. According to PD-L1 status and number of Tumor Infiltrating Lymphocytes (TILs), the cancer microenvironment can be classified into four types reflecting immune resistance, ignorance, induction and tolerance. However, an extended tissue characterization of the immune contexture and its predictive/prognostic value in NSCLC remain elusive. The aim of the present investigation was to determine whether immunologically defined classes of NSCLC differentially impact on clinical outcome.

Methods

Histologic sections of NSCLC samples surgically removed to untreated 51 ADC and 69 SCC and 8 ADC and 10 SCC patients receiving Nivolumab were included. PD-L1 (clones 28-8 and SP142) was measured by immunoperoxidase (H-score) and immunofluorescence (QIF). The n/mm2 and intra-, peri-tumor or invasive margin localization of TILs subpopulations were computed establishing cut off values relative to each phenotype. Immunohistochemical data and clinical records were subjected to Kaplan Meier analysis.

Results

ADC cases had 2-fold higher CD3pos and 1.8-fold lower CD4pos cells compared to SCC and TILs-rich ADC had 10 months’ increase in OS vs –poor (p < 0.01). EGFR mutation conditioned a lower intratumor density of TILs. The frequency of type I (PD-L1high TILshigh) contexture was low (14.6%) while > 1/3 of NSCLC samples displayed type II (PD-L1low/neg TILslow), reflecting immune exhaustion. The proportion of type III (PD-L1high TILslow) and IV (PD-L1low/neg TILshigh) immune categories, with relatively increased Nks and Tregs, was similar. NSCLC type III had the highest OS (35.5 mos.) and PFS (25.7) while in type II immune ignorant cases OS and PFS were respectively 21.7 and 12. Independently from immune categories, patients with PD-1low and high CD8/CD3 ratio had 11 mos. gain in OS (p < 0.01) compared to the reverse counterpart. Accordingly, PD-L1high and PD-1low characterized 86% of patients responsive to nivolumab.

Conclusions

In a dynamic PD-L1 milieu a concomitant intrinsic or therapeutically induced decay of PD-1 receptor allows TILs to escape from PD-L1 pressure and delays tumor progression, improving OS.

Clinical trial identification

Legal entity responsible for the study

University Hospital of Parma, Medicine

Funding

University of Parma

Disclosure

All authors have declared no conflicts of interest.