免疫選択による空間と時間の転移の進化

Mihaela Angelova¹, Bernhard Mlecnik², Angela Vasaturo¹

¹INSERM, Laboratory of Integrative Cancer Immunology, Sorbonne Université, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Centre de Recherche des Cordeliers, 75006 Paris, France.

Cell

|October 16, 2018

まとめ

転移性大腸がんにおける腫瘍の進化は,局所的な免疫微環境によって形作られる. 免疫脱出メカニズムを理解することは効果的ながん免疫療法の開発の鍵です

科学分野:

腫瘍学
免疫学
癌の転移

背景:

免疫微環境は腫瘍の進化と進行に大きな影響を与える.
結腸直腸がん (CRC) の転移は,腫瘍細胞と宿主免疫の複雑な相互作用を伴う.
免疫媒介による選択圧力の理解は,治療戦略の改善に不可欠です.

研究の目的:

結腸直腸がんの異なった転移部位における免疫微環境が腫瘍の進化をどのように形作っているかを調査する.
進行中の転移病変における免疫脱出のメカニズムを特定する.
再発リスクなどの臨床結果と免疫特性を相関させる.

主な方法:

転移性大腸がん患者の経路分析
免疫細胞の浸透と空間的関係を評価するための多重分析.
ネオアンチゲン減少と免疫編集の遺伝的証拠の評価
腫瘍内および腫瘍外免疫脱出メカニズムの特徴化

主要な成果:

転移におけるクローン進化パターンは,局所的な免疫コンテクストゥールに依存する.
ネオアンチゲン減少と免疫編集が免疫反応部位 (高いImmunoscore) で観察されました.
進行中のクローンは免疫特権を示し腫瘍内外的な脱出メカニズムの両方を利用しました
高い免疫スコア,免疫編集の証拠,低腫瘍負荷は再発リスクの減少と相関する.

結論:

免疫を逃れるクローンによって引き起こされる転移性進行を説明します
免疫媒介による選択は,転移部位における腫瘍の進化を形作る上で重要な役割を果たします.
これらの発見は,がんの拡散に関する洞察を提供し,結腸直腸がんに対する新しい免疫療法薬の開発に情報を提供する.

キーワード:

T細胞クローナル異質性について免疫編集免疫スコア免疫療法メタスタシスマイクロ環境変異再発する

さらに関連する動画

12:03

A Method for Tracking the Time Evolution of Steady-State Evoked Potentials

Published on: May 25, 2019

8.9K

16:14

Trajectory Data Analyses for Pedestrian Space-time Activity Study

Published on: February 25, 2013

14.2K

関連する概念動画

02:55

The Evidence for Evolution

48.2K

Genetic variations accumulating within populations over generations give rise to biological evolution. Evolutionary changes can result in the formation of novel varieties and entire new species. These changes are responsible for the diverse forms of life inhabiting the planet. The evidence for evolution suggests that all living organisms descended from common ancestors.

48.2K

01:17

Space-Time Curvature and the General Theory of Relativity

4.4K

In 1905, Albert Einstein published his special theory of relativity. According to this theory, no matter in the universe can attain a speed greater than the speed of light in a vacuum, which thus serves as the speed limit of the universe.
This has been verified in many experiments. However, space and time are no longer absolute. Two observers moving relative to one another do not agree on the length of objects or the passage of time. The mechanics of objects based on Newton's laws of...

4.4K

01:54

Convergent Evolution

32.9K

Evolution shapes the features of organisms over time, ensuring that they are suited for the environments in which they live. Sometimes, selection pressure leads to the rise of similar but unrelated adaptations in organisms with no recent common ancestors, a process known as convergent evolution.

32.9K

01:32

What is Natural Selection?

129.2K

Natural selection is an evolutionary process in which individuals with survival-promoting traits reproduce at higher rates. These favorable traits become more common within a population or species. Naturally selected traits initially arise via random genetic mutations. In order for selection to occur, there must be variation within a population, the trait controlling the variation must be heritable, and there must be an evolutionary advantage for variation in the trait.

129.2K

01:24

Eukaryotic Evolution

41.4K

The endosymbiont theory is the most widely accepted theory of eukaryotic evolution; however, its progression is still somewhat debated. According to the nucleus-first hypothesis, the ancestral prokaryote first evolved a membrane to enclose DNA and form the nucleus. Conversely, the mitochondria-first hypothesis suggests that the nucleus was formed after endosymbiosis of mitochondria.
Contrary to the endosymbiont theory, the eukaryote-first hypothesis proposes that the simpler prokaryotic and...

41.4K

02:31

Synteny and Evolution

3.8K

John H. Renwick first coined the term “synteny” in 1971, which refers to the genes present on the same chromosomes, even if they are not genetically linked. The species with common ancestry tend to show conserved syntenic regions. Therefore, the concept of synteny is nowadays used to describe the evolutionary relationship between species.
Around 80 million years ago, the human and mice lineages diverged from the common ancestor. During the course of evolution, the ancestral...