Impact of EGFR-TKI Treatment on the Tumor Immune Microenvironment in EGFR Mutation-Positive Non-Small Cell Lung Cancer

• Published in: Clinical cancer research Vol. 26; no. 8; pp. 2037 - 2046
• Main Authors: Isomoto, Kohsuke, Haratani, Koji, Hayashi, Hidetoshi, Shimizu, Shigeki, Tomida, Shuta, Niwa, Takashi, Yokoyama, Toshihide, Fukuda, Yasushi, Chiba, Yasutaka, Kato, Ryoji, Tanizaki, Junko, Tanaka, Kaoru, Takeda, Masayuki, Ogura, Takashi, Ishida, Tadashi, Ito, Akihiko, Nakagawa, Kazuhiko
• Format: Journal Article
• Language: English
• Published: United States 15.04.2020
• Subjects: Adult; Aged; Aged, 80 and over; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - metabolism; Biomarkers, Tumor - immunology; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - pathology; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - genetics; ErbB Receptors - metabolism; Female; Humans; Immune Checkpoint Inhibitors - therapeutic use; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Lymphocytes, Tumor-Infiltrating - immunology; Male; Middle Aged; Mutation; Protein Kinase Inhibitors - therapeutic use; Retrospective Studies; Survival Rate; Treatment Outcome; Tumor Microenvironment - drug effects; Tumor Microenvironment - immunology
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-19-2027

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.