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Impact of EGFR-TKI Treatment on the Tumor Immune Microenvironment in EGFR Mutation-Positive Non-Small Cell Lung Cancer
Ist Teil von
Clinical cancer research, 2020-04, Vol.26 (8), p.2037-2046
Ort / Verlag
United States
Erscheinungsjahr
2020
Quelle
MEDLINE
Beschreibungen/Notizen
The impact of EGFR tyrosine kinase inhibitors (TKI) on the tumor immune microenvironment (TME) in non-small cell lung cancer (NSCLC) is unclear.
We retrospectively identified 138 patients with
-mutated NSCLC who underwent rebiopsy after progression during EGFR-TKI treatment. PD-L1 and CD73 expression in tumor cells and tumor-infiltrating lymphocyte (TIL) density at baseline and after progression were determined by IHC. Tumor mutation burden (TMB) was determined by next-generation sequencing.
The proportion of patients with a PD-L1 expression level of ≥50% (high) increased from 14% before to 28% after EGFR-TKI (
= 0.0010). Whereas CD8
and FOXP3
TIL densities were significantly lower after EGFR-TKI treatment than before, CD8
TIL density was maintained in tumors with a high PD-L1 expression level. Expression of CD73 in tumor cells after EGFR-TKI treatment was higher than that before in patients with a high PD-L1 expression level. TMB tended to be higher after EGFR-TKI treatment than before (3.3→4.1 mutations/Mbp,
= 0.0508). Median progression-free survival for subsequent treatment with antibodies to PD-1 was longer for patients with a high than for those with a low PD-L1 expression after EGFR-TKI (7.1 vs. 1.7 months,
= 0.0033), and two of five patients whose PD-L1 expression level changed from low to high after EGFR-TKI treatment achieved a PFS of >6 months.
EGFR-TKI treatment was associated with changes in the TME of
-mutated NSCLC, and such changes may provide clues for optimization of subsequent PD-1 inhibitor treatment.