In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 5565-5565
Abstract:
Background Previous studies indicated that alteration of MDM2/4 was related to poor response even hyper-progressive disease (HPD) to immune checkpoint inhibitors (ICI) therapy. Meanwhile, ICI monotherapy showed low effective rate in hepatocellular carcinoma (HCC), it is still unclear that whether it was associated with HPD-related gene mutation such as MDM2/4. Herein, we analyzed characteristic of MDM2/4 mutation in HCC from tumor immune microenvironment (TIME), to explore the underlying mechanism. Methods Gene mutation of 2615 patients with HCC was analyzed by next generation sequencing (NGS) in 3D Medicines, a laboratory accredited by CAP and Clinical Laboratory Improvement Amendments (CLIA), from Octomber 2017 to May 2020, 68 tumor tissue samples were collected for analysis of TIME, including CD8+ T cells, CD68+HLA-DR+ M1 macrophages and CD68+HLA-DR- M2 macrophages, CD56bright and CD56dim NK cells infiltrated in the tumor tissue, which were detected by multiple fluorescence immunohistochemistry (mICH). Results Among these patients with HCC, 19.54% (511/2615) were mutated in gene MDM2/4, 18.9% (493/2165), 0.7% (18/2165) were MDM2 and MDM4, respectively. The 68 samples were divided into two groups, including group with wild type MDM2/4, and group with MDM2/4 alterations. Analysis of immune cell infiltration revealed that almost all of these immune cells we detected were less infiltrated into tumor tissue of patients with MDM2/4 mutation than without MDM2/4 mutation. What’s more, the most significant difference between patients with and without MDM2/4 alteration was infiltration of CD56dim NK cells (p & lt;0.001). Conclusion The poor response to ICI monotherapy may associated with the high proportion of alteration in gene MDM2/4, which was characterized by low infiltration of immune cells, especially effective NK cells. Citation Format: Xinjun Wang, Hushan Zhang, Yuan Yang, Hang Du, Jingling Tang. Analysis of immune landscape in hepatocellular carcinoma patients with MDM2/4 mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5565.
Type of Medium:
Online Resource
ISSN:
1538-7445
DOI:
10.1158/1538-7445.AM2022-5565
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2022
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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