ANGPTL2-mediated epigenetic repression of MHC-I in tumor cells accelerates tumor immune evasion

被引：6

作者：

Kadomatsu, Tsuyoshi ^{[1
,2
,10
]}

Hara, Chiaki ^{[1
,3
]}

Kurahashi, Ryoma ^{[3
]}

Horiguchi, Haruki ^{[1
,2
,4
]}

Morinaga, Jun ^{[1
,2
]}

Miyata, Keishi ^{[1
]}

Kurano, Sohtaro ^{[1
,5
]}

Kanemaru, Hisashi ^{[6
]}

Fukushima, Satoshi ^{[6
]}

Araki, Kimi ^{[2
,7
]}

Baba, Masaya ^{[8
]}

Linehan, W. Marston ^{[9
]}

Kamba, Tomomi ^{[3
]}

Oike, Yuichi ^{[1
,2
,10
]}

机构：

[1] Kumamoto Univ, Grad Sch Med Sci, Dept Mol Genet, Kumamoto, Japan

[2] Kumamoto Univ, Ctr Metab Regulat Hlth Aging CMHA, Grad Sch Med Sci, Kumamoto, Japan

[3] Kumamoto Univ, Grad Sch Med Sci, Dept Urol, Kumamoto, Japan

[4] Kumamoto Univ, Grad Sch Med Sci, Dept Aging & Geriatr Med, Kumamoto, Japan

[5] Kumamoto Univ, Grad Sch Med Sci, Dept Gastroenterol & Hepatol, Kumamoto, Japan

[6] Kumamoto Univ, Grad Sch Med Sci, Dept Dermatol & Plast Surg, Kumamoto, Japan

[7] Kumamoto Univ, Inst Resource Dev & Anal, Div Dev Genet, Kumamoto, Japan

[8] Kumamoto Univ, Int Res Ctr Med Sci IRCMS, Kumamoto, Japan

[9] NCI, Ctr Canc Res, Urol Oncol Branch, Bethesda, MD USA

[10] Kumamoto Univ, Grad Sch Med Sci, Dept Mol Genet, Honjo 1-1-1,Chuo Ku, Kumamoto 8608556, Japan

来源：

MOLECULAR ONCOLOGY | 2023年 / 17卷 / 12期

关键词：

ANGPTL2; MHC-I; PRC2; tumor immune evasion; ANGIOPOIETIN-LIKE PROTEIN-2; ACQUIRED-RESISTANCE; PD-1; BLOCKADE; EXPRESSION; RECRUITMENT; ANGPTL2; ROLES;

D O I：

10.1002/1878-0261.13490

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Loss or downregulation of major histocompatibility complex class I (MHC-I) contributes to tumor immune evasion. We previously demonstrated that angiopoietin-like protein 2 (ANGPTL2) promotes tumor progression using a Xp11.2 translocation renal cell carcinoma (tRCC) mouse model. However, molecular mechanisms underlying ANGPTL2 tumor-promoting activity in the tRCC model remained unclear. Here, we report that ANGPTL2 deficiency in renal tubular epithelial cells slows tumor progression in the tRCC mouse model and promotes activated CD8(+) T-cell infiltration of kidney tissues. We also found that Angptl2-deficient tumor cells show enhanced interferon gamma-induced expression of MHC-I and increased susceptibility to CD8(+) T-cell-mediated anti-tumor immune responses. Moreover, we provide evidence that the ANGPTL2-alpha 5 beta 1 integrin pathway accelerates polycomb repressive complex 2-mediated repression of MHC-I expression in tumor cells. These findings suggest that ANGPTL2 signaling in tumor cells contributes to tumor immune evasion and that suppressing that signaling in tumor cells could serve as a potential strategy to facilitate tumor elimination by T-cell-mediated anti-tumor immunity.

引用

页码：2637 / 2658

页数：22

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