1404P - Immune microenvironment could be responsible for response to immune checkpoint inhibitors among NSCLC patients with various EGFR mutation types

Background

Previous studies indicated that clinical outcome of ICI therapy were various for NSCLC with different types of EGFR mutation, and its mechanism remains yet to be further investigated. We analysed from tumour immune microenvironment (TIME), to explore the underlying mechanism.

Methods

Gene mutation and TMB of 508 patients with NSCLC was analysed by next generation sequencing (NGS) in our hospital from May 2018 to December 2019, 40 tumour tissue samples were collected for further analysis, expression of PD-L1 was detected by using Dako PD-L1 IHC 22C3 pharmDx, CD8⁺ T cells, CD68⁺HLA-DR⁺ M1 macrophages and CD68⁺HLA-DR^- M2 macrophages, CD56^bright and CD56^dim NK cells infiltrated in the tumor tissue were detected by multiple fluorescence immunohistochemistry (mICH). These patients are still being followed up. Statistical analysis was performed using GraphPad Prism (version 7.01) and SPSS version 21.0 (SPSS,Inc.).

Results

44% (224/508) patients with EGFR mutation, 30% (68/224), 31% (70/224), 38% (86/224) were EGFR exon19 deletion, exon21 L858R point mutation and some other EGFR mutations, respectively. The 40 samples were divided into four groups, including group with wild type EGFR, exon19 deletion mutation, exon21 L858R point mutation and other EGFR mutations. Lower TMB level were displayed in three groups with EGFR mutation (p<0.05), but higher TMB level was found in exon19 deletion mutation than exon21 L858R point mutation group (no significant). Furthermore, among immune cells, CD8⁺T cells was the least immune cell types appeared in tumour microenvironment of all groups. M2 macrophages and CD56^bright NK cells infiltrated more in EGFR mutation groups than in EGFR wild type (p<0.05). More M2 macrophages infiltration in group with exon 19 deletion mutation (p<0.05). Lower percent of PD-L1 positive expression (Tumor Proportion Score, TPS≥1%) were found in EGFR mutation groups, especially, in exon19 deletion mutation group (p<0.05).

Conclusions

The different response to ICI therapy for NSCLC patient with different types of EGFR mutation mainly associated with factors of TIME, such as M2 macrophages.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.