ELCC 2017: Specific Immune Cell Profiles Potentially Identify Patients With Lung Cancer Responsive to Anti–PD-1 Immunotherapy

Key Points

  • Patients with adenocarcinoma having a higher population of TILs in the microenvironment experienced a 10-month increase in overall survival compared to patients with low levels of TILs.
  • The subtype of patients with PD-L1–high and PD-1–low suggested a favorable response to immunotherapy, with 86% of these patients responding to nivolumab.
  • The NSCLC type III specimens showed a relationship with improved survival; patients with this type experienced median OS of 36.5 months and PFS of 27.6 months compared to OS of 25.7 months and PFS of 16.1 months in patients with type II specimens that were immune therapy–naive.

An investigation of immune cell subtypes in the tumor microenvironment of patients with lung adenocarcinoma and squamous cell carcinoma (SCC) identified an immune subgroup that associates with prolonged patient survival and may be prognostic of response to nivolumab, according to findings presented by Mazzaschi et al at the 2017 European Lung Cancer Conference (ELCC) in Geneva, Switzerland (Abstract 2O).

Lead author Giulia Mazzaschi, MD, Department of Medicine, University Hospital of Parma, in Parma, Italy, and colleagues conducted this study to determine the putative impact of immunologically defined classes of non–small cell lung cancer (NSCLC) on clinical outcome following immunotherapy. Her research team investigated histologic sections of NSCLC samples surgically obtained from an untreated cohort of 51 patients with adenocarcinoma and 69 patients with SCC histology, and sections from 8 patients with adenocarcinoma and 10 patients with SCC recruited to receive nivolumab.

Immunoperoxidase (H-score) and immunofluorescence were used to determine programmed death-ligand 1 (PD-L1 [clones 28-8, 22C3 and SP142]) levels. The n/mm2 and intra-, peri-tumor, and invasive margin localization of tumor-infiltrating lymphocytes (TILs) subpopulations were computed to establish cut-off values for each phenotype.

Findings

Kaplan Meier analysis of the immunohistochemical data and clinical records demonstrated that adenocarcinoma cases were twofold higher in CD3-positiveand 1.8-fold lower in CD4-positive cells compared to SCC samples. Patients with adenocarcinoma having a higher population of TILs in the microenvironment experienced a 10-month increase in overall survival (OS) compared to patients with low levels of TILs (P < .01).

The investigators determined the intratumoral density of TILs to be lower in specimens harboring an EGFR mutation.

The frequency of type I (PD-L1–high, TIL–high) contexture was low and was observed in just 14.6% of samples in this series. Type II (PD-L1–low/negative, TIL-low) was detected in more than a third of NSCLC samples, reflecting immune exhaustion. In this series, a similar proportion of type III (PD-L1–high, TILs-low; increased natural killer and granzyme B–positive cytotoxic cells) and type IV (PD-L1–low/negative, TIL-high; enriched in T-regulatory cells) immune categories was observed.

The NSCLC type III specimens showed a relationship with improved survival; patients with this type experienced median OS of 36.5 months and progression-free survival (PFS) of 27.6 months compared to OS of 25.7 months and PFS of 16.1 months in patients with type II specimens that were immune therapy–naive. Patients having programmed cell death protein 1 (PD-1)-low levels plus a high CD8/CD3 ratio showed prolonged OS of 11 months compared to patients having PD-1–high levels together with low CD8/CD3 ratios (P < .01). The subtype of patients with PD-L1–high and PD-1–low suggested a favorable response to immunotherapy, with 86% of these patients responding to nivolumab.

Conclusions

The authors conducted tissue characterization of the immune contexture and determined which subgroups associated with improved OS and response to nivolumab immunotherapy. Based on the findings, they suggest that, 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, thus improving OS.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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