Ferroptosis Signature Shapes the Immune Profiles to Enhance the Response to Immune Checkpoint Inhibitors in Head and Neck Cancer

被引：31

作者：

Chung, Chih-Hung ^{[1
,2
,3
]}

Lin, Chun-Yu ^{[4
,5
,6
,7
,8
,9
]}

Chen, Chih-Yu ^{[9
]}

Hsueh, Chun-Wei ^{[5
]}

Chang, Yao-Wen ^{[9
]}

Wang, Chen-Chi ^{[11
,12
,13
]}

Chu, Pen-Yuan ^{[11
,14
]}

Tai, Shyh-Kuan ^{[11
,14
]}

Yang, Muh-Hwa ^{[1
,2
,3
,4
,9
,10
,15
]}

机构：

[1] Natl Yang Ming Chiao Tung Univ, Taiwan Int Grad Program Mol Med, Taipei 115201, Taiwan

[2] Acad Sinica, Taipei 115201, Taiwan

[3] Natl Yang Ming Chiao Tung Univ, Inst Clin Med, Taipei 112304, Taiwan

[4] Natl Yang Ming Chiao Tung Univ, Dept Biol Sci & Technol, Hsinchu 300093, Taiwan

[5] Natl Yang Ming Chiao Tung Univ, Inst Bioinformat & Syst Biol, Hsinchu 300093, Taiwan

[6] Natl Yang Ming Chiao Tung Univ, Inst Data Sci & Engn, Hsinchu 300093, Taiwan

[7] Natl Yang Ming Chiao Tung Univ, Ctr Intelligent Drug Syst & Smart Biodevices, Hsinchu 300093, Taiwan

[8] Kaohsiung Med Univ, Sch Dent, Kaohsiung 807378, Taiwan

[9] Natl Yang Ming Chiao Tung Univ, Canc Progress Res Ctr, Taipei 112304, Taiwan

[10] Natl Yang Ming Chiao Tung Univ, Dept Biotechnol & Lab Sci Med, Taipei 112304, Taiwan

[11] Natl Yang Ming Chiao Tung Univ, Sch Med, Taipei 112304, Taiwan

[12] Taichung Vet Gen Hosp, Dept Otolaryngol Head & Neck Surg, Taichung 40705, Taiwan

[13] Natl Chung Hsing Univ, Coll Med, Dept Postbaccalaureate Med, Taichung 40227, Taiwan

[14] Taipei Vet Gen Hosp, Dept Otolaryngol, Taipei 112201, Taiwan

[15] Taipei Vet Gen Hosp, Dept Oncol, Taipei 112201, Taiwan

来源：

ADVANCED SCIENCE | 2023年 / 10卷 / 15期

关键词：

ferroptosis; head and neck cancer; programmed death ligand 1; SQUAMOUS-CELL CARCINOMA; INFLAMMATION; THERAPY; CALCIUM; DEATH; PEMBROLIZUMAB; CHEMOTHERAPY; RESISTANCE; CETUXIMAB; RECURRENT;

D O I：

10.1002/advs.202204514

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

As a type of immunogenic cell death, ferroptosis participates in the creation of immunoactive tumor microenvironments. However, knowledge of spatial location of tumor cells with ferroptosis signature in tumor environments and the role of ferroptotic stress in inducing the expression of immune-related molecules in cancer cells is limited. Here the spatial association of the transcriptomic signatures is demonstrated for ferroptosis and inflammation/immune activation located in the invasive front of head and neck squamous cell carcinoma (HNSCC). The association between ferroptosis signature and inflammation/immune activation is more prominent in HPV-negative HNSCC compared to HPV-positive ones. Ferroptotic stress induces PD-L1 expression through reactive oxygen species (ROS)-elicited NF-kappa B signaling pathway and calcium influx. Priming murine HNSCC with the ferroptosis inducer sensitizes tumors to anti-PD-L1 antibody treatment. A positive correlation between the ferroptosis signature and the active immune cell profile is shown in the HNSCC samples. This study reveals a subgroup of ferroptotic HNSCC with immune-active signatures and indicates the potential of priming HNSCC with ferroptosis inducers to increase the antitumor efficacy of immune checkpoint inhibitors.

引用

页数：16