Neoadjuvant and adjuvant immune checkpoint blockade (ICB) have recently become standard of care 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.
A total of 185 treatment-naive early-stage NSCLC patients, that underwent upfront surgical treatment between 2006 and 2018 at Hospital del Mar were included. Core biopsies from the surgical specimens were included in a tissue microarray. Immunohistochemistry for CD3, CD4, CD8, CD68, CD80, CD103, FOXP3, PD-1, PD-L1, PDL2 and HLA class II 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 resident memory (CD103+) immune cells (using the median as cut-off): 1) PD-L1- /CD103-; 2) PD-L1-/CD103+; 3) PD-L1+/CD103-; 4) PD-L1+/CD103+. TIME characteristics and immune markers were statistically compared based on clinicopathological and molecular features and survival outcomes.
We found elevated levels of T cell markers (CD3+, CD4+, CD8+ cells), functional immune markers (FOXP3+ cells) as well as, higher HLA-II tumor membrane expression in LUADs (p<0.05 for all). In contrast, LUSCs displayed higher percentage of intratumor macrophages (CD68+ cells) as well as, higher PD-L1 and PD-L2 tumor membrane expression (p<0.05 for all). PD-L1 positive (≥1%) LUADs exhibited an augmented infiltration of T cells (CD3+, CD4+, CD8+ cells) along with increase of FOXP3+ cells, resident memory cells (CD103+) and macrophages (CD68+) (p<0.05 for all). Enrichment of T cells (CD3+, CD8+ cells), regulatory T cells (FOXP3+ cells) and macrophages (CD68+ cells) was observed in the CD103+/PD-L1+ group (p<0.05 for all), while T helper cells (CD4+), antigen experienced immune cells (PD-1+) and CD80+ immune cells were higher in the CD103+/PD-L1- (p<0.05 for all).
TIME analysis in resected NSCLC highlighted differences by histology, PD-L1 expression and molecular subgroups. Biomarker studies might aid to individually tailor adjuvant treatment in early-stage NSCLC.
The authors.
Has not received any funding.
A. Taus Garcia: Non-Financial Interests, Personal, Other: Roche, BMS, MSD, GSK, AstraZeneca, Pfizer. B. Bellosillo Paricio: Non-Financial Interests, Personal, Other: Amgen, AstraZeneca, Biocartis, Janssen, Merck-Serono, Novartis, Qiagen, F. Hoffman-La Roche, ThermoFisher, Pfizer, BMS. E. Arriola: Non-Financial Interests, Personal, Other: Roche, BMS, MSD, AstraZeneca, Pfizer, Boehringer Ingelheim, Lilly, Takeda. All other authors have declared no conflicts of interest.