Abstract 1186P
Background
Chromosome locus 11q13 is frequently amplified in several of solid tumors including non-small cell lung cancer (NSCLC). It was reported that the frequent amplification of chromosome 11q13 in solid tumors were associated with clinical worsen response to immune checkpoint inhibitors or even hyper-progression disease (HPD). However, the underlying mechanism for the association was still ambiguous. Herein, based on data of 10582 Chinse patients with NSCLC, we analyzed characteristics of FGF3/4/19, CCND1 which located in chromosome 11q13, and explored the potential mechanism HPD related to the amplification in chromosome 11q13 in NSCLC patients.
Methods
The formalin-fixed paraffin-embedded specimens of NSCLC patients who have underwent next-generation sequencing (NGS) and tumor immune microenvironment (TIME) detection from January 2017 to February 2021, were included in this study. Tumor mutational burden (TMB) measured by a 733 gene panel, and detected expression of PD-L1 by using Dako PD-L1 IHC 22C3 pharmDx. Detection of TIME by multiple fluorescence immunohistochemistry (mICH), including CD8+ T cells, two subtypes of tumor associated macrophages (TAM) and two subtypes of NK cells infiltrated in the tumor biopsies. Statistical analysis was performed using GraphPad Prism (version 7.01) and SPSS version 21.0 (SPSS,Inc.).
Results
Among the 10582 patients, 3.9% (410/10582) patients were carried amplification in gene FGF3/4/19 and CCND1. 2935 and 3185 were available for TMB and PD-L1 expression analysis, respectively. No difference was found in level of PD-L1 expression between patients with and without these gene amplification. However, higher TMB was found in patients with FGF3/4/19 and CCND1 amplification than without (p<0.05). Further analysis was performed in results of TIME, and results showed that infiltration of CD8+T cells was similar between the two groups, while infiltration of M1 tumor associated macrophages, both CD56dim and CD56bright NK cell significantly insufficient in patient with amplification in 11q13 region.
Conclusions
The underlying explanation may be related to insufficient infiltration of immune cells, especially M1 macrophages and NK cells.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
H. Zhang, W. Duan: Financial Interests, Institutional, Full or part-time Employment: 3D Medicines Inc. All other authors have declared no conflicts of interest.