Diverse genetic-driven immune landscapes dictate tumor progression through distinct mechanisms

被引：147

作者：

Bezzi, Marco ^{[1
]}

Seitzer, Nina ^{[1
]}

Ishikawa, Tomoki ^{[1
]}

Reschke, Markus ^{[1
]}

Chen, Ming ^{[1
]}

Wang, Guocan ^{[1
]}

Mitchell, Caitlin ^{[1
]}

Ng, Christopher ^{[1
]}

Katon, Jesse ^{[1
]}

Lunardi, Andrea ^{[1
]}

Signoretti, Sabina ^{[2
,3
]}

Clohessy, John G. ^{[1
,4
]}

Zhang, Jiangwen ^{[5
]}

Pandolfi, Pier Paolo ^{[1
]}

机构：

[1] Harvard Med Sch, Dept Med, Beth Israel Deaconess Med Ctr, Canc Res Inst,Beth Israel Deaconess Canc Ctr, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA

[3] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[4] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Preclin Murine Pharmacogenet Facil, Boston, MA USA

[5] Univ Hong Kong, Sch Biol Sci, Hong Kong, Hong Kong, Peoples R China

来源：

NATURE MEDICINE | 2018年 / 24卷 / 02期

关键词：

RESISTANT PROSTATE-CANCER; SUPPRESSOR-CELLS; CELLULAR SENESCENCE; MYELOID CELLS; DOUBLE-BLIND; MICROENVIRONMENT; METASTASIS; MACROPHAGES; NEUTROPHILS; MELANOMA;

D O I：

10.1038/nm.4463

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Multiple immune-cell types can infiltrate tumors and promote progression and metastasis through different mechanisms, including immunosuppression. How distinct genetic alterations in tumors affect the composition of the immune landscape is currently unclear. Here, we characterized the immune-cell composition of prostate cancers driven by the loss of the critical tumor suppressor gene Pten, either alone or in combination with the loss of Trp53, Zbtb7a or Pml. We observed a striking quantitative and qualitative heterogeneity that was directly dependent on the specific genetic events in the tumor and ranged from 'cold', noninflamed tumors to massively infiltrated landscapes-results with important therapeutic implications. Further, we showed these qualitative differences in transcriptomic analysis of human prostate cancer samples. These data suggest that patient stratification on the basis of integrated genotypic-immunophenotypic analyses may be necessary for successful clinical trials and tailored precision immunological therapies.

引用

页码：165 / +

页数：13

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