Chen Zhangguo, John Jessy, Wang Jing H
UPMC Hillman Cancer Center, Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States.
Department of Immunology, University of Pittsburgh, Pittsburgh, PA, United States.
Front Oncol. 2022 Oct 18;12:995434. doi: 10.3389/fonc.2022.995434. eCollection 2022.
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., ) and mutations of tumor suppressor genes (e.g., ). 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.
免疫检查点抑制剂（ICIs）彻底改变了癌症治疗方式，包括对头颈部鳞状细胞癌（HNSCCs）的治疗；然而，只有一小部分HNSCC患者对ICI有反应，而大多数患者则无反应。这种不同反应背后的机制仍未完全了解。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反应率。HNSCC表现出高度的基因异质性，表现为癌基因的突变或扩增（例如 ）以及肿瘤抑制基因的突变（例如 ）。HNSCC的免疫肿瘤微环境（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））的相对丰度方面也有显著差异，这代表了高度的免疫异质性。在这里，我们简要讨论异质性ICI反应如何可能归因于肿瘤内在因素，包括肿瘤细胞中的基因、转录和功能变异，以及宿主内在因素，包括TME的细胞组成（例如CD8 TILs和TAMs），以及CD8 TILs的T细胞受体（TCR）库中的宿主内在差异。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。
