Progression of carcinogen-induced fibrosarcomas is associated with the accumulation of naïve CD4+ T cells via blood vessels and lymphatics.
Progression of carcinogen-induced fibrosarcomas is associated with the accumulation of naïve CD4+ T cells via blood vessels and lymphatics.
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DOI：
10.1002/ijc.28556
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发表时间：
2014-05-01
影响因子：
6.4
通讯作者：
Gallimore, Awen
中科院分区：
文献类型：
--
作者：
Ondondo, Beatrice;Jones, Emma;Hindley, James;Cutting, Scott;Smart, Kathryn;Bridgeman, Hayley;Matthews, Katherine K.;Ladell, Kristin;Price, David A.;Jackson, David G.;Godkin, Andrew;Ager, Ann;Gallimore, Awen
肿瘤微环境包括新形成的血液和淋巴管，它们决定了肿瘤肿块内淋巴细胞的流入、滞留和离开。因此，通过影响肿瘤内淋巴细胞的组成，这些血管影响适应性免疫系统对肿瘤的反应方式，促进或损害有效的抗肿瘤免疫。在我们的研究中，我们利用致癌物诱导的纤维肉瘤小鼠模型来检测肿瘤进展过程中肿瘤浸润淋巴细胞的组成。特别是，我们试图确定CD4+Foxp3+调节性T细胞（Tregs）是否在肿瘤进展过程中变得富集，从而有助于肿瘤驱动的免疫抑制。但事实并非如此，因为naïve T细胞的意外积累导致肿瘤内Tregs和效应CD4+ T细胞的比例实际上下降了。然而，我们没有发现抗原驱动这些T细胞迁移或它们参与抗肿瘤免疫反应的证据。我们的数据支持淋巴细胞可以通过异常形成的血液和淋巴管进入肿瘤的观点。这些发现表明，同时靶向肿瘤的脉管系统和淋巴系统将改变进入肿瘤肿块的淋巴细胞亚群的平衡。考虑到肿瘤免疫学的这一方面可能对实体癌免疫治疗的成功至关重要。有什么新鲜事吗?众所周知，肿瘤微环境可损害抗肿瘤免疫反应。罪魁祸首通常被认为是各种抑制细胞和细胞因子。然而，在这项研究中，作者发现看似无害的naïve T细胞也可能发挥重要作用-仅仅通过在肿瘤内积累和可能的竞争激活效应细胞。更好地了解肿瘤微环境产生的信号可能使研究人员能够改变这种T细胞池，从而增强免疫反应。
The tumor microenvironment comprises newly formed blood and lymphatic vessels which shape the influx, retention and departure of lymphocytes within the tumor mass. Thus, by influencing the intratumoral composition of lymphocytes, these vessels affect the manner in which the adaptive immune system responds to the tumor, either promoting or impairing effective antitumor immunity. In our study, we utilized a mouse model of carcinogen‐induced fibrosarcoma to examine the composition of tumor‐infiltrating lymphocytes during tumor progression. In particular, we sought to determine whether CD4+Foxp3+ regulatory T cells (Tregs) became enriched during tumor progression thereby contributing to tumor‐driven immunosuppression. This was not the case as the proportion of Tregs and effector CD4+ T cells actually declined within the tumor owing to the unexpected accumulation of naïve T cells. However, we found no evidence for antigen‐driven migration of these T cells or for their participation in an antitumor immune response. Our data support the notion that lymphocytes can enter tumors via aberrantly formed blood and lymphatic vessels. Such findings suggest that targeting both the tumor vasculature and lymphatics will alter the balance of lymphocyte subpopulations that enter the tumor mass. A consideration of this aspect of tumor immunology may be critical to the success of solid cancer immunotherapies. What's new? It is well known that a tumors' microenvironment can impair the anti‐tumor immune response. The culprits are usually assumed to be various suppressor cells and cytokines. In this study, however, the authors found that seemingly innocuous, naïve T cells may also play a significant role—simply by accumulating and possibly out‐competing activated effector cells within the tumor. A better understanding of the signals produced by the tumor microenvironment may allow researchers to alter this T‐cell pool, thus enhancing the immune response.
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影响因子：
11.2
作者：
Hindley, James P.;Jones, Emma;Gallimore, Awen M.
通讯作者：
Gallimore, Awen M.
DOI：
10.1083/jcb.115.1.85
发表时间：
1991-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mebius RE;Streeter PR;Brevé J;Duijvestijn AM;Kraal G
通讯作者：
Kraal G
DOI：
10.1084/jem.194.7.953
发表时间：
2001-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Weninger W;Crowley MA;Manjunath N;von Andrian UH
通讯作者：
von Andrian UH
DOI：
10.1084/jem.20092454
发表时间：
2010-08-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Thompson ED;Enriquez HL;Fu YX;Engelhard VH
通讯作者：
Engelhard VH
DOI：
10.1084/jem.192.10.1425
发表时间：
2000-11-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gretz JE;Norbury CC;Anderson AO;Proudfoot AE;Shaw S
通讯作者：
Shaw S