急性髓系白血病化療耐藥通過MHC分子和B7家族成員與抗腫瘤免疫應答降低相關

2024年6月，首都醫科大學附屬北京世紀壇醫院，北京大學醫學部基礎醫學院，北京航空航天大學臨床醫學院航天中心醫院，中國醫學科學院中國中醫基礎理論（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研究團隊在《Discover Oncology》上發表論文：

“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MHC分子和B7家族成員與抗腫瘤免疫應答降低相關”

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)仍然具有挑戰性。B7家族蛋白的異常表達與腫瘤逃逸有關。我們想知道B7家族蛋白在AML CDR中的改變是否進一步支持腫瘤逃逸。本文建立了AML阿糖胞苷耐藥細胞株U937/Ara-C，并報道了MHC分子和B7家族成員的表達情況。HLA-ABC在兩種細胞系上高度表達相似。MIC (MHC class I chain related) A/B和B7-H6在U937表面適度表達，而被U937/Ara-C顯著降低。U937/Ara-C可增強B7-H1和B7-H7的表達。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共培養相比，U937/Ara-C培養的外周血單個核細胞的細胞毒性降低，表現為顆粒酶B和穿孔素產生水平降低，TNF-α和乳酸脫氫酶分泌減少。綜上所述，AML CDR進一步規避了可能通過MHC分子和B7家族成員的抗腫瘤免疫應答。

該論文中，從人AML細胞系U937、耐藥AML細胞系U937/Ara-C、藥物處理后的細胞的體外培養是使用Ausbian特級胎牛血清完成的。欲了解或購買Ausbian特級胎牛血清可以聯系北京締一生物400-166-8600.