Inflammatory dendritic cells restrain CD11b+CD4+CTLs via CD200R in human NSCLC

被引：2

作者：

Lin, Mingjie ^{[1
,2
]}

Chen, Di ^{[2
,3
]}

Shao, Zheyu ^{[1
,2
]}

Liu, Qinyuan ^{[1
,2
]}

Hao, Zhixing ^{[1
,2
]}

Xin, Zhongwei ^{[1
,2
]}

Chen, Yongyuan ^{[1
,2
]}

Wu, Wenxuan ^{[2
,4
]}

Chen, Xiaoke ^{[1
,2
]}

He, Teng ^{[2
,5
]}

Wu, Dang ^{[2
]}

Wu, Pin ^{[1
,2
]}

机构：

[1] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Thorac Surg, Hangzhou 310009, Peoples R China

[2] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Key Lab Tumor Microenvironm & Immune Therapy Zheji, Hangzhou, 310009, Peoples R China

[3] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Radiat Oncol, Hangzhou 310009, Peoples R China

[4] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Gastrointestinal Surg, Hangzhou 310009, Peoples R China

[5] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Infect Dis, Hangzhou 310009, Peoples R China

来源：

CELL REPORTS | 2024年 / 43卷 / 02期

基金：

中国国家自然科学基金;

关键词：

CD4(+) T-CELLS; RESIDENT MEMORY; LYMPHOCYTES; EXPRESSION; TISSUE; MELANOMA; HELPER;

D O I：

10.1016/j.celrep.2024.113767

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

CD4+ cytotoxic T lymphocytes (CD4+ CTLs) are suggested to play a crucial role in inflammatory diseases, including cancer, but their characteristics in human non -small cell lung cancer (NSCLC) remain unknown. Here, using the cell surface marker CD11b, we identify CD11b+CD4+ CTLs as a cytotoxic subset of CD4+ T cells in multiple tissues of NSCLC patients. In addition, tumor -infiltrating CD11b+CD4+ CTLs show a dysfunctional phenotype with elevated expression of CD200 receptor (CD200R), a negatively immunomodulatory receptor. CD4+ regulatory T (Treg) cells restrain the anti -tumor role of CD11b+CD4+ CTLs via CD200. Mechanistically, inflammatory dendritic cells promote the CD200R expression of CD11b+CD4+ CTLs by secreting interleukin-1b (IL -1b). Finally, we demonstrate that CD200 blockade can revive the tumor -killing role of CD11b+CD4+ CTLs and prolong the survival of tumor -bearing mice. Taken together, our study identifies CD11b+CD4+ CTLs in NSCLC with decreased cytotoxicity that can be reinvigorated by CD200 blockade, suggesting that targeting CD200 is a promising immunotherapy strategy in NSCLC.

引用

页数：22

共 50 条

[1] CD4+ T cell help in cancer immunology and immunotherapy [J].

Borst, Jannie ;

Ahrends, Tomasz ;

Babala, Nikolina ;

Melief, Cornelis J. M. ;

Kastenmueller, Wolfgang .

NATURE REVIEWS IMMUNOLOGY, 2018, 18 (10) :635-647

[2] CD4 CTL: Living up to the challenge [J].

Cheroutre, Hilde ;

Husain, Mohammad Mushtaq .

SEMINARS IN IMMUNOLOGY, 2013, 25 (04) :273-281

[3] CD200 promotes immunosuppression in the pancreatic tumor microenvironment [J].

Choueiry, Fouad ;

Torok, Molly ;

Shakya, Reena ;

Agrawal, Kriti ;

Deems, Anna ;

Benner, Brooke ;

Hinton, Alice ;

Shaffer, Jami ;

Blaser, Bradley W. ;

Noonan, Anne M. ;

Williams, Terence M. ;

Dillhoff, Mary ;

Conwell, Darwin L. ;

Hart, Phil A. ;

Cruz-Monserrate, Zobeida ;

Bai, Xue-Feng ;

Carson III, William E. ;

Mace, Thomas A. .

JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2020, 8 (01)

[4] CD200 expression suppresses natural killer cell function and directly inhibits patient anti-tumor response in acute myeloid leukemia [J].

Coles, S. J. ;

Wang, E. C. Y. ;

Man, S. ;

Hills, R. K. ;

Burnett, A. K. ;

Tonks, A. ;

Darley, R. L. .

LEUKEMIA, 2011, 25 (05) :792-799

[5] Cytotoxic human CD4+ T cells [J].

de Berg, Pablo J. van ;

van Leeuwen, Ester M. ;

Ten Berge, Ineke J. ;

van Lier, Rene .

CURRENT OPINION IN IMMUNOLOGY, 2008, 20 (03) :339-343

[6] A CD8α- Subset of CD4+SLAMF7+Cytotoxic T Cells Is Expanded in Patients With IgG4-Related Disease and Decreases Following Glucocorticoid Treatment [J].

Della-Torre, Emanuel ;

Bozzalla-Cassione, Emanuele ;

Sciorati, Clara ;

Ruggiero, Eliana ;

Lanzillotta, Marco ;

Bonfiglio, Silvia ;

Mattoo, Hamid ;

Perugino, Cory A. ;

Bozzolo, Enrica ;

Rovati, Lucrezia ;

Arcidiacono, Paolo Giorgio ;

Balzano, Gianpaolo ;

Lazarevic, Dejan ;

Bonini, Chiara ;

Falconi, Massimo ;

Stone, John H. ;

Dagna, Lorenzo ;

Pillai, Shiv ;

Manfredi, Angelo A. .

ARTHRITIS & RHEUMATOLOGY, 2018, 70 (07) :1133-1143

[7] Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus [J].

Gebhardt, Thomas ;

Wakim, Linda M. ;

Eidsmo, Liv ;

Reading, Patrick C. ;

Heath, William R. ;

Carbone, Francis R. .

NATURE IMMUNOLOGY, 2009, 10 (05) :524-530

[8] Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing [J].

Guo, Xinyi ;

Zhang, Yuanyuan ;

Zheng, Liangtao ;

Zheng, Chunhong ;

Song, Jintao ;

Zhang, Qiming ;

Kang, Boxi ;

Liu, Zhouzerui ;

Jin, Liang ;

Xing, Rui ;

Gao, Ranran ;

Zhang, Lei ;

Dong, Minghui ;

Hu, Xueda ;

Ren, Xianwen ;

Kirchhoff, Dennis ;

Roider, Helge Gottfried ;

Yan, Tiansheng ;

Zhang, Zemin .

NATURE MEDICINE, 2018, 24 (07) :978-+

[9] Overexpression of CD200 is a Stem Cell-Specific Mechanism of Immune Evasion in AML [J].

Herbrich, Shelley ;

Baran, Natalia ;

Cai, Tianyu ;

Weng, Connie ;

Aitken, Marisa J. L. ;

Post, Sean M. ;

Henderson, Jared ;

Shi, Chunhua ;

Havranek, Ondrej ;

Richard-Carpentier, Guillame ;

Sauvageau, Guy ;

Baggerly, Keith ;

Al-Atrash, Gheath ;

Davis, R. Eric ;

Daver, Naval ;

Zha, Dongxing ;

Konopleva, Marina .

JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2021, 9 (07)

[10] Induction of tumoricidal function in CD4+ T cells is associated with concomitant memory and terminally differentiated phenotype [J].

Hirschhorn-Cymerman, Daniel ;

Budhu, Sadna ;

Kitano, Shigehisa ;

Liu, Cailian ;

Zhao, Feng ;

Zhong, Hong ;

Lesokhin, Alexander M. ;

Avogadri-Connors, Francesca ;

Yuan, Jianda ;

Li, Yanyun ;

Houghton, Alan N. ;

Merghoub, Taha ;

Wolchok, Jedd D. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2012, 209 (11) :2113-2126

← 1 2 3 4 5 →