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诊断性活检通常不会诱导 Merkel 细胞癌的肿瘤内 CD8+T 细胞浸润。

Diagnostic biopsy does not commonly induce intratumoral CD8 T cell infiltration in Merkel cell carcinoma.

机构信息

Dermatology/Medicine, University of Washington, Seattle, Washington, United States of America.

出版信息

PLoS One. 2012;7(7):e41465. doi: 10.1371/journal.pone.0041465. Epub 2012 Jul 31.

Abstract

BACKGROUND

Merkel cell carcinoma is a polyomavirus-associated cancer that is strongly linked with T lymphocyte immune suppression in epidemiologic studies. CD8+ T cell infiltration into MCC tumors (intratumoral) has recently been shown to be strongly predictive of improved survival. In contrast, the presence of CD8+ T cells at the border of the tumor (peritumoral) had no independent prognostic value. Spontaneous regression has been reported for MCC approximately one thousand times more often than would be expected given the frequency of this cancer. Many of these events began shortly after biopsy, and in some cases lymphocytic infiltration was described.

METHODOLOGY/PRINCIPAL FINDINGS: To determine whether CD8+ lymphocyte infiltration in MCC tumors is commonly altered by biopsy.33 MCC patients who had microscopic confirmation of MCC on both an initial biopsy and a re-excision specimen were included in this study. Intratumoral and peritumoral CD8 lymphocyte infiltration was quantitated using immunohistochemistry and compared using the paired t-test in biopsy versus re-excision samples. There was a trend toward increased CD8 infiltration after biopsy in a peritumoral ('stalled') pattern (p = 0.08), however, biopsy was not associated with a significant increase in CD8 T cells in the clinically more important intratumoral location (p = 0.58).

CONCLUSIONS/SIGNIFICANCE: The initial diagnostic biopsy for MCC does not commonly alter intratumoral CD8+ T cell infiltration, suggesting it does not directly induce immunologic recognition of this cancer. Because CD8 infiltration is typically stable after biopsy, this parameter may be useful to assess the efficacy of future immune therapies for this virus-associated, immunogenic, often-lethal cancer.

摘要

背景

默克尔细胞癌是一种与多瘤病毒相关的癌症,在流行病学研究中与 T 淋巴细胞免疫抑制密切相关。最近的研究表明,CD8+T 细胞浸润 MCC 肿瘤(肿瘤内)强烈预示着生存改善。相比之下,肿瘤边缘(肿瘤周围)的 CD8+T 细胞存在没有独立的预后价值。MCC 已经被报道大约有一千次自发消退,这比这种癌症的频率所预期的要多得多。这些事件中的许多在活检后不久就开始了,在某些情况下还描述了淋巴细胞浸润。

方法/主要发现:为了确定 MCC 肿瘤中的 CD8+淋巴细胞浸润是否通常因活检而改变。本研究纳入了 33 名 MCC 患者,他们的初始活检和再次切除标本均经显微镜证实存在 MCC。使用免疫组织化学定量分析肿瘤内和肿瘤周围的 CD8 淋巴细胞浸润,并在活检与再次切除样本中使用配对 t 检验进行比较。在肿瘤周围(“停滞”)模式下,活检后 CD8 浸润呈增加趋势(p=0.08),然而,活检与肿瘤内更重要的位置(p=0.58)的 CD8 T 细胞显著增加无关。

结论/意义:MCC 的初始诊断性活检通常不会改变肿瘤内 CD8+T 细胞浸润,表明它不会直接诱导对这种癌症的免疫识别。由于 CD8 浸润在活检后通常保持稳定,因此该参数可能有助于评估未来针对这种病毒相关、免疫原性、通常致命的癌症的免疫治疗的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b38d/3409202/da5909069d6a/pone.0041465.g001.jpg

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