Changes in PD-L1 expression according to tumor infiltrating lymphocytes of acquired EGFR-TKI resistant EGFR-mutant nonsmall- cell lung cancer

Backgrounds: EGFR-mutant non-small cell lung cancer (NSCLC) that developed acquired resistance to EGFR-tyrosine kinase (TKI) are potential candidates for programmed death 1 (PD1) inhibitor. Results: TPS≥1% for PD-L1 and low CD8+ TIL in post-TKI tumor showed a trend for a lower PFS of EGFR-TKIs (14.2 vs 9.9 months; P = 0.060) (cohort A). Only 2 of 22 specimens (9.1%) with an acquired EGFR exon 20 T790M mutation exhibited in post-TKI TPS≥50% for PD-L1. The degree in post-TKI tumor of PD-L1 expression was varied in 19 patients (40.5%), with 10 (21.2%) showing higher levels in the resistant biopsy (cohort B). Among the post-TKI high TPS groups, median PFS with low post- TKI CD8⁺ TIL scores treated with EGFR-TKIs (6.6 months) was significantly lower than that for the other patients (14.2 months; P = 0.015). Conclusions: The change of PD-L1 expression was accompanied by dynamic change in CD8+ TILs and might reflect diverse mechanism of resistance to EGFR-TKI therapy. Material and Methods: We identified 69 patients (cohort A) with sufficient post- TKI tumor tissues and 47 patients (cohort B) with paired tumor tissues available. TPS for PD-L1 expression of tumor cells and CD8⁺ TILs score in tumor specimens were determined by immunohistochemistry.