Heterogeneous Tumor-Immune Microenvironments among Differentially Growing Metastases in an Ovarian Cancer Patient

被引：396

作者：

Jimenez-Sanchez, Alejandro ^{[1
]}

Memon, Danish ^{[1
,2
]}

Pourpe, Stephane ^{[10
]}

Veeraraghavan, Harini ^{[3
]}

Li, Yanyun ^{[4
]}

Vargas, Hebert Alberto ^{[5
]}

Gill, Michael B. ^{[1
]}

Park, Kay J. ^{[6
]}

Zivanovic, Oliver ^{[7
]}

Konner, Jason ^{[8
]}

Ricca, Jacob ^{[4
]}

Zamarin, Dmitriy ^{[4
,10
]}

Walther, Tyler ^{[10
]}

Aghajanian, Carol ^{[8
]}

Wolchok, Jedd D. ^{[4
,9
,10
,11
,12
]}

Sala, Evis ^{[5
]}

Merghoub, Taha ^{[4
]}

Snyder, Alexandra ^{[10
,11
]}

Miller, Martin L. ^{[1
]}

机构：

[1] Univ Cambridge, Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England

[2] EMBL, European Bioinformat Inst, Wellcome Genome Campus, Cambridge CB10 1SD, England

[3] Mem Sloan Kettering Canc Ctr, Dept Med Phys, 1275 York Ave, New York, NY 10065 USA

[4] Mem Sloan Kettering Canc Ctr, Ludwig Collaborat Swim Amer Lab, 1275 York Ave, New York, NY 10065 USA

[5] Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10065 USA

[6] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10065 USA

[7] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, 1275 York Ave, New York, NY 10065 USA

[8] Mem Sloan Kettering Canc Ctr, Dept Med, Gynecol Med Oncol Serv, 1275 York Ave, New York, NY 10065 USA

[9] Mem Sloan Kettering Canc Ctr, Parker Inst Canc Immunotherapy, 1275 York Ave, New York, NY 10065 USA

[10] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10065 USA

[11] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA

[12] Weill Cornell Grad Sch Med Sci, Immunol & Microbial Pathogenesis Programs, New York, NY 10065 USA

来源：

CELL | 2017年 / 170卷 / 05期

关键词：

T-CELL; INTRATUMOR HETEROGENEITY; ACQUIRED-RESISTANCE; EXPRESSION; GENE; GENERATION; PREDICTION; MUTATIONS; EVOLUTION; RESPONSES;

D O I：

10.1016/j.cell.2017.07.025

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

We present an exceptional case of a patient with high-grade serous ovarian cancer, treated with multiple chemotherapy regimens, who exhibited regression of some metastatic lesions with concomitant progression of other lesions during a treatment-free period. Using immunogenomic approaches, we found that progressing metastases were characterized by immune cell exclusion, whereas regressing and stable metastases were infiltrated by CD8(+) and CD4(+) T cells and exhibited oligoclonal expansion of specific T cell subsets. We also detected CD8(+) T cell reactivity against predicted neoepitopes after isolation of cells from a blood sample taken almost 3 years after the tumors were resected. These findings suggest that multiple distinct tumor immune microenvironments co-exist within a single individual and may explain in part the heterogeneous fates of metastatic lesions often observed in the clinic post-therapy.

引用

页码：927 / +

页数：32

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