In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 4639-4639
Abstract:
Background: Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, has shown promising efficacy on wild-type RAS metastatic colorectal cancer (CRC) patients. Cetuximab demonstrates anti-cancer effect via NK cells and subsequent immunogenic cell death. Chemotherapy or targeted therapy may change immune surface markers. Methods: We characterized a panel of 6 CRC cell lines with different genetic features. The impacts of interferon-γ (IFN-γ) on cell surface expressions of major histocompatibility complex (MHC) class I (including subtypes), MHC class II (including subtypes), MHC class 1 related molecule A (MICA, the NK cell ligand), Intercellular Adhesion Molecule 1 (ICAM-1, the immunoglobulin superfamily), EGFR, and Chondroitin Sulfate Proteoglycan 4 (CSPG-4, pericyte attaching marker) before and after treatment with IFN-γ (100 U/ml, 48 h) were explored in selected cell lines Results: Among six human colon cancer cell lines analyzed, DLD-1, HCT15, and LoVo exhibited no expression of HLA-A and HLA-B,C. Colo-320 demonstrated both low HLA-A and HLA-B,C expression and irresponsive to IFN-γ stimulation. In contrast, both HT-29 and SW-480 showed low HLA-A and HLA-B,C expression, but the expression of both HLA-A and HLA-B,C was corrected after IFN-γ stimulation. All six cell lines possessed low MHC class II expression and irresponsive to IFN-γ stimulation. All six cell lines possessed low MIC expression and irresponsive to IFN-γ stimulation. All six cell lines showed low ICAM-1 expression, but only HT-29 and SW-480 were responsive to IFN-γ stimulation. LOVO and SW-480 demonstrated high EGFR expression and irresponsive to IFN-γ stimulation. Only HT-29 possessed high CSPG-4 expression. Conclusion: These findings reveal that regardless of their genetic features, all six CRC cell lines possess a phenotype that may allow them to escape cytotoxic T and NK cell attack. Table Cell LineMSICIMPKRASBRAFPI3KCATP53DLD-1MSI+G13DWTE545KS241FHCT-15MSI+G13DWTE545KS241FLOVOMSI-G13DWTWTWTCOLO-320MSS-WTWTWTR248WHT-29MSS+WTV600EP449TR273HSW-480MSS-G12VWTWTR273H Citation Format: Yi-Hsin Liang, Yen-Cheng Lin, Kuo-Hsin Chen, Chiu-Hwa Kao, Ann-Lii Cheng, Kun-Huei Yeh, Chien-Chung Chang. HLA and NKG2D ligand abnormalities and IFN-γ unnresponsiveness in human colorectal carcinoma cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4639. doi:10.1158/1538-7445.AM2017-4639
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2017-4639
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2017
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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