Differentiation and Regulation of T(H) Cells: A Balancing Act for Cancer Immunotherapy.
Differentiation and Regulation of T(H) Cells: A Balancing Act for Cancer Immunotherapy.
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DOI：
10.3389/fimmu.2021.669474
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发表时间：
2021
影响因子：
7.3
通讯作者：
Kodumudi K
中科院分区：
文献类型：
--
作者：
Basu A;Ramamoorthi G;Albert G;Gallen C;Beyer A;Snyder C;Koski G;Disis ML;Czerniecki BJ;Kodumudi K
目前癌症免疫治疗的成功已经引起了对肿瘤中TH细胞亚群的关注，其对于直接通过自身或通过刺激细胞毒性T细胞活性激活抗肿瘤应答至关重要。然而，在肿瘤环境中存在免疫抑制性促肿瘤发生TH亚群进一步导致调节TH细胞介导的免疫应答的复杂性。在这篇综述中，我们概述了TH细胞的多方面积极和消极影响，重点是各种免疫细胞对不同TH细胞亚型的调节，以及矛盾信号的微妙平衡如何影响癌症免疫治疗的整体成功。我们专注于调控网络，包括树突状细胞诱导的活化的CD 4 + TH 1细胞和随后引发的CD 8+细胞毒性T细胞，沿着交叉抗炎和促肿瘤发生的TH 2细胞活性。我们进一步讨论了其他肿瘤浸润性免疫细胞，如免疫刺激性TH 9和Tfh细胞，免疫抑制性Treg细胞，以及TH 17功能的双重性如何有助于肿瘤中抗-与促肿瘤TH反应的平衡。我们强调了CD 4 + TH 1免疫应答对新抗原/肿瘤驱动因子的发展知识，当前免疫治疗策略对CD 4 + TH 1免疫的影响，以及如何进一步探索TH细胞亚型的对抗作用以扩大患者的免疫治疗成功。理解CD 4 + TH细胞调节的细微差别和支持抗-与促肿瘤性TH亚型之间平衡作用的分子框架对于合理设计免疫疗法至关重要，所述免疫疗法可以绕过治疗逃逸以最大化免疫疗法的潜力。
Current success of immunotherapy in cancer has drawn attention to the subsets of TH cells in the tumor which are critical for activation of anti-tumor response either directly by themselves or by stimulating cytotoxic T cell activity. However, presence of immunosuppressive pro-tumorigenic TH subsets in the tumor milieu further contributes to the complexity of regulation of TH cell-mediated immune response. In this review, we present an overview of the multifaceted positive and negative effects of TH cells, with an emphasis on regulation of different TH cell subtypes by various immune cells, and how a delicate balance of contradictory signals can influence overall success of cancer immunotherapy. We focus on the regulatory network that encompasses dendritic cell-induced activation of CD4+ TH1 cells and subsequent priming of CD8+ cytotoxic T cells, along with intersecting anti-inflammatory and pro-tumorigenic TH2 cell activity. We further discuss how other tumor infiltrating immune cells such as immunostimulatory TH9 and Tfh cells, immunosuppressive Treg cells, and the duality of TH17 function contribute to tip the balance of anti- vs pro-tumorigenic TH responses in the tumor. We highlight the developing knowledge of CD4+ TH1 immune response against neoantigens/oncodrivers, impact of current immunotherapy strategies on CD4+ TH1 immunity, and how opposing action of TH cell subtypes can be explored further to amplify immunotherapy success in patients. Understanding the nuances of CD4+ TH cells regulation and the molecular framework undergirding the balancing act between anti- vs pro-tumorigenic TH subtypes is critical for rational designing of immunotherapies that can bypass therapeutic escape to maximize the potential of immunotherapy.
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影响因子：
4.8
作者：
Adotevi, Olivier;Dosset, Magalie;Borg, Christophe
通讯作者：
Borg, Christophe
影响因子：
64.5
作者：
Benci JL;Xu B;Qiu Y;Wu TJ;Dada H;Twyman-Saint Victor C;Cucolo L;Lee DSM;Pauken KE;Huang AC;Gangadhar TC;Amaravadi RK;Schuchter LM;Feldman MD;Ishwaran H;Vonderheide RH;Maity A;Wherry EJ;Minn AJ
通讯作者：
Minn AJ
影响因子：
16.6
作者：
Ahrends, Tomasz;Busselaar, Julia;Borst, Jannie
通讯作者：
Borst, Jannie
影响因子：
24.8
作者：
Ahmadzadeh, Mojgan;Pasetto, Anna;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.
影响因子：
11.2
作者：
Ahrends, Tomasz;Babala, Nikolina;Borst, Jannie
通讯作者：
Borst, Jannie