Impact of EGFR-TKI Treatment on the Tumor Immune Microenvironment in EGFR Mutation–Positive Non–Small Cell Lung Cancer
| Autor: | Shuta Tomida, Takashi Ogura, Tadashi Ishida, Shigeki Shimizu, Hidetoshi Hayashi, Koji Haratani, Masayuki Takeda, Junko Tanizaki, Ryoji Kato, Kohsuke Isomoto, Yasutaka Chiba, Akihiko Ito, Kazuhiko Nakagawa, Takashi Niwa, Kaoru Tanaka, Yasushi Fukuda, Toshihide Yokoyama |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research biology business.industry Lymphocyte FOXP3 medicine.disease respiratory tract diseases 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research biology.protein medicine Carcinoma Immunohistochemistry Epidermal growth factor receptor Lung cancer business Survival rate Tyrosine kinase |
| Zdroj: | Clinical Cancer Research. 26:2037-2046 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | Purpose: The impact of EGFR tyrosine kinase inhibitors (TKI) on the tumor immune microenvironment (TME) in non–small cell lung cancer (NSCLC) is unclear. Experimental Design: We retrospectively identified 138 patients with EGFR-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. Results: The proportion of patients with a PD-L1 expression level of ≥50% (high) increased from 14% before to 28% after EGFR-TKI (P = 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, P = 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, P = 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. Conclusions: EGFR-TKI treatment was associated with changes in the TME of EGFR-mutated NSCLC, and such changes may provide clues for optimization of subsequent PD-1 inhibitor treatment. |
| Databáze: | OpenAIRE |
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