Targeting STAT3 signaling reduces immunosuppressive myeloid cells in head and neck squamous cell carcinoma

被引：33

作者：

Bu, Lin-Lin ^{[1
,2
,3
]}

Yu, Guang-Tao ^{[1
,2
]}

Deng, Wei-Wei ^{[1
,2
]}

Mao, Liang ^{[1
,2
]}

Liu, Jian-Feng ^{[1
,2
]}

Ma, Si-Rui ^{[1
,2
]}

Fan, Teng-Fei ^{[1
,2
]}

Hall, Bradford ^{[4
]}

Kulkarni, Ashok B. ^{[4
]}

Zhang, Wen-Feng ^{[1
,2
,3
]}

Sun, Zhi-Jun ^{[1
,2
,3
,4
]}

机构：

[1] Minist Educ, State Key Lab Breeding Base Basic Sci Stomatol, Wuhan, Peoples R China

[2] Minist Educ, Key Lab Oral Biomed, Wuhan, Peoples R China

[3] Wuhan Univ, Sch & Hosp Stomatol, Dept Oral Maxillofacial Head Neck Oncol, Wuhan, Peoples R China

[4] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA

来源：

ONCOIMMUNOLOGY | 2016年 / 5卷 / 05期

基金：

中国国家自然科学基金;

关键词：

Head and neck squamous cell carcinoma; myeloid-derived suppressor cells; STAT3; tumor-associated macrophages; IMMUNE-RESPONSES; TGF-BETA; CANCER; INHIBITION; TRANSDUCERS; ACTIVATORS; BLOCKADE; DELETION; EVASION; INNATE;

D O I：

10.1080/2162402X.2015.1130206

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cumulative evidence suggests that constitutively activated signal transducer and activator of transcription (STAT3) may contribute to sustaining immunosuppressive status, and that inhibiting STAT3 signaling represents a potential strategy to improve antitumor immunity. In the present study, we observed that high levels phosphorylated of STAT3 are significantly associated with the markers for both myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) in human head and neck squamous cell carcinoma (HNSCC). Additionally, we showed that targeting STAT3 signaling with a tolerable selective inhibitor S3I-201 significantly decreased immature myeloid cells such as MDSCs, TAMs and iDCs in genetically defined mice HNSCC model. These findings highlight that targeting STAT3 signaling may be effective to enhance antitumor immunity via myeloid suppressor cells in HNSCC.

引用

页数：11

共 44 条

[1] Immunologic Consequences of Signal Transducers and Activators of Transcription 3 Activation in Human Squamous Cell Carcinoma [J].

Albesiano, Emilia ;

Davis, Meghan ;

See, Alfred P. ;

Han, James E. ;

Lim, Michael ;

Pardoll, Drew M. ;

Kim, Young .

CANCER RESEARCH, 2010, 70 (16) :6467-6476

[2]

[Anonymous], 2018, ANTI-CANCER DRUG, DOI [DOI 10.3322/caac.20115, DOI 10.1097/CAD.0000000000000617]

[3] Loss of TGF-β signaling and PTEN promotes head and neck squamous cell carcinoma through cellular senescence evasion and cancer-related inflammation [J].

Bian, Y. ;

Hall, B. ;

Sun, Z-J ;

Molinolo, A. ;

Chen, W. ;

Gutkind, J. S. ;

Waes, C. V. ;

Kulkarni, A. B. .

ONCOGENE, 2012, 31 (28) :3322-3332

[4] Regulation of immune responses by L- arginine metabolism [J].

Bronte, V ;

Zanovello, P .

NATURE REVIEWS IMMUNOLOGY, 2005, 5 (08) :641-654

[5] A Novel Strategy for Inducing the Antitumor Effects of Triterpenoid Compounds: Blocking the Protumoral Functions of Tumor-Associated Macrophages via STAT3 Inhibition [J].

Fujiwara, Yukio ;

Takeya, Motohiro ;

Komohara, Yoshihiro .

BIOMED RESEARCH INTERNATIONAL, 2014, 2014

[6] Targeting STAT3 phosphorylation by neem leaf glycoprotein prevents immune evasion exerted by supraglottic laryngeal tumor induced M2 macrophages [J].

Goswami, K. K. ;

Barik, A. S. ;

Sarkar, M. ;

Bhowmick, A. ;

Biswas, J. ;

Bose, A. ;

Baral, R. .

MOLECULAR IMMUNOLOGY, 2014, 59 (02) :119-127

[7] Targeting of interleukin-13 receptor α2 for treatment of head and neck squamous cell carcinoma induced by conditional deletion of TGF-β and PTEN signaling [J].

Hall, Bradford ;

Nakashima, Hideyuki ;

Sun, Zhi-Jun ;

Sato, Yuki ;

Bian, Yansong ;

Husain, Syed R. ;

Puri, Raj K. ;

Kulkarni, Ashok B. .

JOURNAL OF TRANSLATIONAL MEDICINE, 2013, 11

[8] Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells [J].

Jinushi, Masahisa ;

Chiba, Shigeki ;

Yoshiyama, Hironori ;

Masutomi, Kenkichi ;

Kinoshita, Ichiro ;

Dosaka-Akita, Hirotoshi ;

Yagita, Hideo ;

Takaoka, Akinori ;

Tahara, Hideaki .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (30) :12425-12430

[9] Involvement of STAT3 in immune evasion during lung tumorigenesis [J].

Kida, Hiroshi ;

Ihara, Shoichi ;

Kumanogoh, Atsushi .

ONCOIMMUNOLOGY, 2013, 2 (01)

[10] IL-6-STAT3 controls intracellular MHC class II αβ dimer level through cathepsin S activity in dendritic cells [J].

Kitamura, H ;

Kamon, H ;

Sawa, SI ;

Park, SJ ;

Katunuma, N ;

Ishihara, K ;

Murakami, M ;

Hirano, T .

IMMUNITY, 2005, 23 (05) :491-502

← 1 2 3 4 5 →