An intra-tumoral niche maintains and differentiates stem-like CD8 T cells

被引：604

作者：

Jansen, Caroline S. ^{[1
]}

Prokhnevska, Nataliya ^{[1
]}

Master, Viraj A. ^{[1
,2
]}

Sanda, Martin G. ^{[1
,2
]}

Carlisle, Jennifer W. ^{[2
,3
]}

Bilen, Mehmet Asim ^{[2
,3
]}

Cardenas, Maria ^{[1
]}

Wilkinson, Scott ^{[4
]}

Lake, Ross ^{[4
]}

Sowalsky, Adam G. ^{[4
]}

Valanparambil, Rajesh M. ^{[5
,6
]}

Hudson, William H. ^{[5
,6
]}

McGuire, Donald ^{[5
,6
]}

Melnick, Kevin ^{[1
]}

Khan, Amir I. ^{[1
]}

Kim, Kyu ^{[1
]}

Chang, Yun Min ^{[5
]}

Kim, Alice ^{[1
]}

Filson, Christopher P. ^{[1
,2
]}

Alemozaffar, Mehrdad ^{[1
,2
]}

Osunkoya, Adeboye O. ^{[1
,2
,7
]}

Mullane, Patrick ^{[7
]}

Ellis, Carla ^{[7
]}

Akondy, Rama ^{[5
,6
]}

Im, Se Jin ^{[5
,6
]}

Kamphorst, Alice O. ^{[8
]}

Reyes, Adriana ^{[1
]}

Liu, Yuan ^{[2
,9
]}

Kissick, Haydn ^{[1
,2
,5
,6
]}

机构：

[1] Emory Univ, Sch Med, Dept Urol, Atlanta, GA 30322 USA

[2] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA

[3] Emory Univ, Sch Med, Dept Hematol & Oncol, Atlanta, GA USA

[4] NCI, Lab Genitourinary Canc Pathogenesis, Bethesda, MD 20892 USA

[5] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA

[6] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA

[7] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA

[8] Icahn Sch Med Mt Sinai, Dept Oncol Sci, Precis Immunol Inst, New York, NY 10029 USA

[9] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA

来源：

NATURE | 2019年 / 576卷 / 7787期

基金：

美国国家卫生研究院;

关键词：

TERTIARY LYMPHOID STRUCTURES; ANTI-PD-L1; ANTIBODY; PD-1; BLOCKADE; SURVIVAL; PREDICTOR; RESPONSES; DENSITY; SAFETY;

D O I：

10.1038/s41586-019-1836-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Tumour-infiltrating lymphocytes are associated with a survival benefit in several tumour types and with the response to immunotherapy(1-8). However, the reason some tumours have high CD8 T cell infiltration while others do not remains unclear. Here we investigate the requirements for maintaining a CD8 T cell response against human cancer. We find that CD8 T cells within tumours consist of distinct populations of terminally differentiated and stem-like cells. On proliferation, stem-like CD8 T cells give rise to more terminally differentiated, effector-molecule-expressing daughter cells. For many T cells to infiltrate the tumour, it is critical that this effector differentiation process occur. In addition, we show that these stem-like T cells reside in dense antigen-presenting-cell niches within the tumour, and that tumours that fail to form these structures are not extensively infiltrated by T cells. Patients with progressive disease lack these immune niches, suggesting that niche breakdown may be a key mechanism of immune escape.

引用

页码：465 / +

页数：25

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