Intratumoral heterogeneity in cancer progression and response to immunotherapy

被引：539

作者：

Vitale, Ilio ^{[1
,2
]}

Shema, Efrat ^{[3
]}

Loi, Sherene ^{[4
,5
]}

Galluzzi, Lorenzo ^{[6
,7
,8
,9
,10
]}

机构：

[1] IIGM Italian Inst Genom Med, IRCSS Candiolo, Turin, Italy

[2] IRCCS, FPO, Candiolo Canc Inst, Candiolo, Italy

[3] Weizmann Inst Sci, Dept Biol Regulat, Rehovot, Israel

[4] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[5] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia

[6] Weill Cornell Med Coll, Dept Radiat Oncol, New York, NY 10065 USA

[7] Sandra & Edward Meyer Canc Ctr, New York, NY 10065 USA

[8] Caryl & Israel Englander Inst Precis Med, New York, NY 10021 USA

[9] Yale Sch Med, Dept Dermatol, New Haven, CT 06510 USA

[10] Univ Paris, Paris, France

来源：

NATURE MEDICINE | 2021年 / 27卷 / 02期

基金：

欧洲研究理事会;

关键词：

PD-1; BLOCKADE; T-CELLS; GENETIC-HETEROGENEITY; TUMOR HETEROGENEITY; RESISTANCE; EVOLUTION; LANDSCAPE; REVEALS; INHIBITORS; DYNAMICS;

D O I：

10.1038/s41591-021-01233-9

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：

Most (if not all) tumors emerge and progress under a strong evolutionary pressure imposed by trophic, metabolic, immunological, and therapeutic factors. The relative impact of these factors on tumor evolution changes over space and time, ultimately favoring the establishment of a neoplastic microenvironment that exhibits considerable genetic, phenotypic, and behavioral heterogeneity in all its components. Here, we discuss the main sources of intratumoral heterogeneity and its impact on the natural history of the disease, including sensitivity to treatment, as we delineate potential strategies to target such a detrimental feature of aggressive malignancies. The many levels of heterogeneity within tumors dictate their response to therapy and should be considered in future therapeutic regimes.

引用

页码：212 / 224

页数：13

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