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急性髓系白血病中的化疗耐药与通过主要组织相容性复合体(MHC)分子和B7家族成员介导的抗肿瘤免疫反应降低有关。

Chemotherapy resistance in acute myeloid leukemia is associated with decreased anti-tumor immune response through MHC molecule and B7 family members.

作者信息

Ge Jing, Yin Xiaoxuan, Sun Xin, Kou Liduo, Xue Xin, Ma Juan

机构信息

Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.

College of Basic Medical Science, Peking University Health Science Center, Beijing, 100191, China.

出版信息

Discov Oncol. 2024 Jun 11;15(1):221. doi: 10.1007/s12672-024-01072-3.

Abstract

Acute myeloid leukemia (AML) remains challenging due to chemotherapeutic drug-resistance (CDR). Aberrant expression B7 family proteins are involved in tumors evasion. We wonder whether B7 family protein alteration in AML CDR further supports tumor escape. Here, we establish AML cytarabine-resistant cell line U937/Ara-C and report on the expression MHC molecule and B7 family member. HLA-ABC was highly expressed similarly on both cell lines. MIC (MHC class I chain related) A/B and B7-H6 was moderately expressed on the surface of U937 and decreased dramatically by U937/Ara-C. In contrast, enhanced expression of B7-H1 and B7-H7 by U937/Ara-C was observed. HLA-DR and other B7 family members including CD80, CD86, B7-DC, B7-H2, B7-H3, B7-H4, and B7-H5 were not detected by both cell lines. Compared co-cultured with U937, peripheral blood mononuclear cells showed a decreased cytotoxicity when incubated with U937/Ara-C, as indicated by decreased levels of granzyme B and perforin production, accompanied with less TNF-α and lactate dehydrogenase secretion. In conclusion, AML CDR further evades the anti-tumor immune response which may through MHC molecule and B7 family members.

摘要

由于化疗耐药性(CDR),急性髓系白血病(AML)仍然具有挑战性。B7家族蛋白的异常表达与肿瘤逃逸有关。我们想知道AML CDR中B7家族蛋白的改变是否进一步支持肿瘤逃逸。在这里,我们建立了AML阿糖胞苷耐药细胞系U937/Ara-C,并报告了MHC分子和B7家族成员的表达情况。HLA-ABC在两种细胞系上均高表达。MIC(MHC I类链相关分子)A/B和B7-H6在U937表面中度表达,而在U937/Ara-C上显著降低。相反,观察到U937/Ara-C使B7-H1和B7-H7的表达增强。两种细胞系均未检测到HLA-DR和其他B7家族成员,包括CD80、CD86、B7-DC、B7-H2、B7-H3、B7-H4和B7-H5。与U937共培养相比,外周血单个核细胞与U937/Ara-C孵育时细胞毒性降低,表现为颗粒酶B和穿孔素产生水平降低,同时TNF-α和乳酸脱氢酶分泌减少。总之,AML CDR可能通过MHC分子和B7家族成员进一步逃避抗肿瘤免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf3d/11166614/7d166f5eb5d7/12672_2024_1072_Fig1_HTML.jpg

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