急性髓系白血病化療耐藥通過(guò)MHC分子和B7家族成員與抗腫瘤免疫應(yīng)答降低相關(guān)

2024年6月，首都醫(yī)科大學(xué)附屬北京世紀(jì)壇醫(yī)院，北京大學(xué)醫(yī)學(xué)部基礎(chǔ)醫(yī)學(xué)院，北京航空航天大學(xué)臨床醫(yī)學(xué)院航天中心醫(yī)院，中國(guó)醫(yī)學(xué)科學(xué)院中國(guó)中醫(yī)基礎(chǔ)理論（1Beijing Shijitan Hospital, Capital Medical University,

2College of
Basic Medical Science, Peking University Health Science Center.

3Aerospace Central Hospital, School of
Clinical Medicine,Peking University Aerospace,

4China Basic Medical Theory of
Chinese Medicine, Academy of
Chinese Medical Sciences,）Juan Ma研究團(tuán)隊(duì)在《Discover Oncology》上發(fā)表論文：

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

“急性髓系白血病化療耐藥通過(guò)MHC分子和B7家族成員與抗腫瘤免疫應(yīng)答降低相關(guān)”

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 cocultured 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：

由于化療耐藥(CDR)，急性髓性白血病(AML)仍然具有挑戰(zhàn)性。B7家族蛋白的異常表達(dá)與腫瘤逃逸有關(guān)。我們想知道B7家族蛋白在AML CDR中的改變是否進(jìn)一步支持腫瘤逃逸。本文建立了AML阿糖胞苷耐藥細(xì)胞株U937/Ara-C，并報(bào)道了MHC分子和B7家族成員的表達(dá)情況。HLA-ABC在兩種細(xì)胞系上高度表達(dá)相似。MIC (MHC class I chain related) A/B和B7-H6在U937表面適度表達(dá)，而被U937/Ara-C顯著降低。U937/Ara-C可增強(qiáng)B7-H1和B7-H7的表達(dá)。HLA-DR及其他B7家族成員CD80、CD86、B7- dc、B7- h2、B7- h3、B7- h4、B7- h5均未檢出。與U937共培養(yǎng)相比，U937/Ara-C培養(yǎng)的外周血單個(gè)核細(xì)胞的細(xì)胞毒性降低，表現(xiàn)為顆粒酶B和穿孔素產(chǎn)生水平降低，TNF-α和乳酸脫氫酶分泌減少。綜上所述，AML CDR進(jìn)一步規(guī)避了可能通過(guò)MHC分子和B7家族成員的抗腫瘤免疫應(yīng)答。

該論文中，從人AML細(xì)胞系U937、耐藥AML細(xì)胞系U937/Ara-C、藥物處理后的細(xì)胞的體外培養(yǎng)是使用Ausbian特級(jí)胎牛血清完成的。欲了解或購(gòu)買(mǎi)Ausbian特級(jí)胎牛血清可以聯(lián)系北京締一生物400-166-8600.