Abstract 91P
Background
Neoadjuvant and adjuvant immune checkpoint blockade (ICB) have recently shown promising results in resectable NSCLC. Yet, biomarkers that inform patient benefit with this approach remain largely unknown. Here, we interrogated the tumor immune microenvironment (TIME) in early-stage NSCLC patients that underwent up-front surgery.
Methods
A total of 188 treatment-naïve early-stage NSCLC patients, that underwent curative surgical treatment between 2006 and 2018 at Hospital del Mar, Barcelona, Spain, were included. None of the patients received adjuvant immunotherapy. Core biopsies from surgical specimens were included in a tissue microarray. Immunohistochemistry of PD-L1, CD3, CD4, CD8, CD68, CD103 and FOXP3 were evaluated by digital image analysis (QuPath software). TIME was categorized into four groups using PD-L1 expression in tumor cells (<1% or ≥1%) and tumor infiltrating lymphocytes (TILs) based on intratumoral CD3 percentage (cut-off calculated using Youden’s index – 26.32%): 1) PD-L1-/TILs -, 2) PD-L1-/TILs+, 3) PD-L1+/TILs-, 4) PD-L1+/TILs+. TIME patterns and immune markers were statistically compared based on clinicopathological and molecular features and survival outcomes.
Results
PD-L1-/TILs+ tumors showed a reduced risk of relapse compared to PD-L1+/TILs+ (p=0.0471). Analysis of immune subpopulations within these tumors showed an increase of CD8+ (cytotoxic T) on both subgroups with a higher proportion in the PD-L1+/TILs+ (p<0.0001). However, FOXP3+ (regulatory T) cells were also higher in PD-L1+/TILs+ (p<0.0001). Thus, conferring an overall increase of CD8/FOXP3 ratio in PD-L1-/TILs+ tumors (p=0.0109). Of note, the CD103+ cells (tissue resident memory) were increased in the PD-L1+/TILs+ category (p<0.0001). PD-L1+/TILs- tumors showed comparable survival with PD-L1+/TILs+ tumors, together with an increase of CD68+ cells (p=0.0055).
Conclusions
T cell subpopulations (CD103+, CD8/FOXP3 ratio) exhibited by PD-L1+/TILs+ tumors suggest the potential role of ICB to revert the TIME towards a favorable immune context and thus, improve survival outcomes. TIME patterns can be used as a tool for tailoring adjuvant strategies.
Legal entity responsible for the study
The authors.
Funding
ISCIII.
Disclosure
A. Taus: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Roche. All other authors have declared no conflicts of interest.