Why the Outcome of Anti-Tumor Immune Responses is Heterogeneous: A Novel Idea in the Context of Immunological Heterogeneity in Cancers.
Why the Outcome of Anti-Tumor Immune Responses is Heterogeneous: A Novel Idea in the Context of Immunological Heterogeneity in Cancers.
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DOI：
10.1002/bies.202000024
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Wang JH
中科院分区：
文献类型：
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作者：
Wang JH
为什么一些宿主能够根除它们的肿瘤，而另一些则屈服于肿瘤的发展，这个问题仍然没有答案。在这里，我提出了一个具有挑衅性的概念，即个体T细胞受体（TCR）库的内在差异可能通过影响肿瘤反应性CD8和/或CD4肿瘤浸润淋巴细胞的频率和/或种类来影响抗肿瘤免疫的结果。这一观点暗示，特定患者的TCR库可能无法提供足够不同的TCR克隆来识别肿瘤抗原，也就是说，“TCR库中的漏洞”可能存在。这一观点可能为进一步剖析不同宿主体内异质抗肿瘤免疫反应的机制提供一个新的视角。除了肿瘤内在异质性和宿主微生物组外，我还讨论了可能不断形成动态TCR库的各种因素。阐明不同个体免疫系统的机制差异将使我们能够更好地利用免疫系统来设计新的个性化癌症免疫疗法。决定癌症免疫异质性的潜在机制仍然难以捉摸。除了肿瘤的内在异质性和环境因素外，t细胞受体（TCR）库的内在差异也可能起作用。提出了“TCR库中的一个漏洞”假说来解释可能显著影响癌症免疫治疗的抗肿瘤反应的异质性。
The question as to why some hosts can eradicate their tumors whilst others succumb to tumor-progression remains unanswered. Here, I propose a provocative concept that intrinsic differences in the T cell receptor (TCR) repertoire of individuals may influence the outcome of anti-tumor immunity by affecting the frequency and/or variety of tumor-reactive CD8 and/or CD4 tumor-infiltrating lymphocytes. This idea implicates that the TCR repertoire in a given patient might not provide sufficiently different TCR clones that can recognize tumor antigens, namely, “a hole in the TCR repertoire” might exist. This idea may provide a novel perspective to further dissect the mechanisms underlying heterogeneous anti-tumor immune responses in different hosts. Besides tumor-intrinsic heterogeneity and host microbiome, I also discuss the various factors that may constantly shape the dynamic TCR repertoire. Elucidating mechanistic differences in different individuals’ immune systems will allow us to better harness immune system to design new personalized cancer immunotherapy. Underlying mechanisms that dictate the immunological heterogeneity in cancers remain elusive. Besides tumor-intrinsic heterogeneity and environmental factors, intrinsic differences in the T-cell receptor (TCR) repertoire may play a role. “A hole in the TCR repertoire” hypothesis is proposed to explain heterogeneity of anti-tumor responses that may significantly impact cancer immunotherapy.
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影响因子：
17.1
作者：
Highfill SL;Cui Y;Giles AJ;Smith JP;Zhang H;Morse E;Kaplan RN;Mackall CL
通讯作者：
Mackall CL
影响因子：
5.1
作者：
Chervin, A. S.;Stone, J. D.;Kranz, D. M.
通讯作者：
Kranz, D. M.
影响因子：
6.4
作者：
Fagnoni, FF;Lozza, L;Robustelli Della Cuna, G
通讯作者：
Robustelli Della Cuna, G
DOI：
10.1073/pnas.1210882109
发表时间：
2012-11-06
影响因子：
11.1
作者：
Holland, Stephen J.;Bartok, Istvan;Dyson, Julian
通讯作者：
Dyson, Julian
DOI：
10.1158/1078-0432.ccr-17-0864
发表时间：
2017-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Fessler JL;Gajewski TF
通讯作者：
Gajewski TF