HPV+和HPV-头颈癌的肿瘤免疫微环境,WIREs Mechanisms of Disease

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HPV+和HPV-头颈癌的肿瘤免疫微环境
WIREs Mechanisms of Disease ( IF 4.6 ) Pub Date : 2021-10-19 , DOI: 10.1002/wsbm.1539
Steven F. Gameiro ₁ , Andris M. Evans ₁ , Joe S. Mymryk _{1,

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Affiliation

人乳头瘤病毒 (HPV) 是头颈部鳞状细胞癌 (HNSCC)（头颈部区域的一组异质性恶性肿瘤）的一个重要且不断增加的部分的病原体。HPV 感染约占所有病例的 25%，其余病例通常由吸烟和过量饮酒引起。这些不同的病因导致 HPV 阳性 (HPV ⁺ ) 和 HPV 阴性 (HPV ^- ) HNSCC 之间存在深刻的临床和免疫学差异，这可能与 HPV ⁺亚型中外源病毒抗原的表达有关。具体而言，与 HPV患者相比，HPV ^{+ HNSCC 患者通常表现出更好的治疗反应}^-疾病，导致更有利的预后，具有更低的复发率和更长的总生存期。重要的是，大量研究表明，HPV ^{+ HNSCC 的肿瘤免疫微环境 (TIME) 与其 HPV}^-对应物具有明显不同的免疫成分。^{与免疫学上更“冷”的 HPV -} TIME 相比， HPV ⁺ TIME 的特征是免疫学“热”，具有更多的免疫浸润、更高水平的 T 细胞活化和更高水平的免疫调节。一般来说，与免疫“冷”对应物相比，具有免疫“热”时间的癌症表现出更好的治疗反应和更好的临床结果。事实上，这种现象在 HPV 中也观察到了⁺ HNSCC 患者，强调 TIME 在影响预后方面的关键作用，并进一步验证利用 TIME 的动员和/或调节的癌症疗法的使用。

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The tumor immune microenvironments of HPV+ and HPV− head and neck cancers

Human papillomaviruses (HPVs) are the etiological agent of a significant, and increasing, fraction of head and neck squamous cell carcinomas (HNSCC)—a heterogenous group of malignancies in the head and neck region. HPV infection accounts for approximately 25% of all cases, with the remainder typically caused by smoking and excessive alcohol consumption. These distinct etiologies lead to profound clinical and immunological differences between HPV-positive (HPV⁺) and HPV-negative (HPV⁻) HNSCC, likely related to the expression of exogenous viral antigens in the HPV⁺ subtype. Specifically, HPV⁺ HNSCC patients generally exhibit better treatment response compared to those with HPV⁻ disease, leading to a more favorable prognosis, with lower recurrence rate, and longer overall survival time. Importantly, a plethora of studies have illustrated that the tumor immune microenvironment (TIME) of HPV⁺ HNSCC has a strikingly distinct immune composition to that of its HPV⁻ counterpart. The HPV⁺ TIME is characterized as being immunologically “hot,” with more immune infiltration, higher levels of T-cell activation, and higher levels of immunoregulation compared to the more immunologically “cold” HPV⁻ TIME. In general, cancers with an immune “hot” TIME exhibit better treatment response and superior clinical outcomes in comparison to their immune “cold” counterparts. Indeed, this phenomenon has also been observed in HPV⁺ HNSCC patients, highlighting the critical role of the TIME in influencing prognosis, and further validating the use of cancer therapies that capitalize on the mobilization and/or modulation of the TIME.

更新日期：2021-10-19

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