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

Abstract

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.

• Authors: Kohsuke Isomoto, Koji Haratani, Hidetoshi Hayashi, Shigeki Shimizu, Shuta Tomida, Takashi Niwa, Toshihide Yokoyama, Yasushi Fukuda, Yasutaka Chiba, Ryoji Kato, Junko Tanizaki, Kaoru Tanaka, Masayuki Takeda, Takashi Ogura, Tadashi Ishida, Akihiko Ito, Kazuhiko Nakagawa
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 26 Issue 8 Pg. 2037-2046 (04 15 2020) ISSN: 1557-3265 [Electronic] United States
• PMID: 31937613 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2020 American Association for Cancer Research.

Chemical References

• B7-H1 Antigen
• Biomarkers, Tumor
• CD274 protein, human
• Immune Checkpoint Inhibitors
• Protein Kinase Inhibitors
• EGFR protein, human
• ErbB Receptors

Topics

• Adult
• Aged
• Aged, 80 and over
• B7-H1 Antigen (antagonists & inhibitors, metabolism)
• Biomarkers, Tumor (immunology)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, immunology, pathology)
• ErbB Receptors (antagonists & inhibitors, genetics, metabolism)
• Female
• Humans
• Immune Checkpoint Inhibitors (therapeutic use)
• Lung Neoplasms (drug therapy, genetics, immunology, pathology)
• Lymphocytes, Tumor-Infiltrating (immunology)
• Male
• Middle Aged
• Mutation
• Protein Kinase Inhibitors (therapeutic use)
• Retrospective Studies
• Survival Rate
• Treatment Outcome
• Tumor Microenvironment (drug effects, immunology)