Why responses to immune checkpoint inhibitors are heterogeneous in head and neck cancers: Contributions from tumor-intrinsic and host-intrinsic factors.
Why responses to immune checkpoint inhibitors are heterogeneous in head and neck cancers: Contributions from tumor-intrinsic and host-intrinsic factors.
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DOI：
10.3389/fonc.2022.995434
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发表时间：
2022
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
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免疫检查点抑制剂（ICIs）已经彻底改变了癌症治疗，包括头颈部鳞状细胞癌（HNSCC）的治疗；然而，只有一部分HNSCC患者对ICI有反应，而大多数患者则没有反应。这种不同反应的潜在机制仍未完全了解。更好地理解这些机制可能会扩大有反应患者的范围，并提高ICI的反应率。HNSCC表现出高度的遗传异质性，表现为癌基因（如PIK3CA）的突变或扩增以及肿瘤抑制基因（如TP53）的突变。HNSCC的肿瘤免疫微环境（TME）在组成以及不同免疫亚群（如CD8肿瘤浸润淋巴细胞（TILs）或肿瘤相关巨噬细胞（TAMs））的相对丰度方面也存在显著差异，这代表了高度的免疫异质性。在此，我们简要讨论了异质性的ICI反应如何可归因于肿瘤内在因素，包括肿瘤细胞在遗传、转录和功能方面的差异，以及宿主内在因素，包括TME的细胞组成（如CD8 TILs和TAMs），以及CD8 TILs的T细胞受体（TCR）库的宿主内在差异。我们还讨论了这些因素对设计HNSCC个性化免疫治疗策略的潜在影响。
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment including in head and neck squamous cell carcinomas (HNSCCs); however, only a fraction of HNSCC patients respond to ICI, whereas the majority fail to do so. The mechanisms underlying such variable responses remain incompletely understood. A better understanding of such mechanisms may broaden the spectrum of responding patients and enhance the rate of ICI response. HNSCCs exhibit a high level of genetic heterogeneity, manifested as mutations or amplifications of oncogenes (e.g., PIK3CA) and mutations of tumor suppressor genes (e.g., TP53). The immune tumor microenvironment (TME) of HNSCCs also varies significantly in composition and in relative abundance of distinct immune subsets such as CD8 tumor-infiltrating lymphocytes (TILs) or tumor-associated macrophages (TAMs), which represents a high degree of immunological heterogeneity. Here, we briefly discuss how heterogeneous ICI responses may be attributed to tumor-intrinsic factors, including genetic, transcriptional, and functional variations in tumor cells, and host-intrinsic factors, including cellular composition of the TME (e.g., CD8 TILs and TAMs), and host-intrinsic differences in the T cell receptor (TCR) repertoire of CD8 TILs. We also discuss the potential impact of these factors on designing strategies for personalized immunotherapy of HNSCCs.
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影响因子：
8
作者：
Du L;Chen X;Cao Y;Lu L;Zhang F;Bornstein S;Li Y;Owens P;Malkoski S;Said S;Jin F;Kulesz-Martin M;Gross N;Wang XJ;Lu SL
通讯作者：
Lu SL
影响因子：
5.2
作者：
Burcher KM;Lantz JW;Gavrila E;Abreu A;Burcher JT;Faucheux AT;Xie A;Jackson C;Song AH;Hughes RT;Lycan T Jr;Bunch PM;Furdui CM;Topaloglu U;D'Agostino RB Jr;Zhang W;Porosnicu M
通讯作者：
Porosnicu M
DOI：
10.1186/s13046-022-02337-x
发表时间：
2022-04-02
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Chen SMY;Popolizio V;Woolaver RA;Ge H;Krinsky AL;John J;Danis E;Ke Y;Kramer Y;Bian L;Nicklawsky AG;Gao D;Liu S;Chen Z;Wang XJ;Wang JH
通讯作者：
Wang JH
影响因子：
8
作者：
通讯作者：
--
影响因子：
3.7
作者：
Buitrago-Perez, Agueda;Hachimi, Mariam;Garcia-Escudero, Ramon
通讯作者：
Garcia-Escudero, Ramon