Purpose

Immune checkpoint inhibitors have recently been approved by the US FDA as first and/or second line therapy in a subset of cancer types. Recent evidence suggests that the quantity of tumor infiltrating lymphocytes (TILs) influences the likelihood of response to immune checkpoint inhibitors. Here, we set out to assess the density of CD8⁺ lymphocytes in a wide range of different cancer types and subtypes.

Methods

The density of CD8⁺ lymphocytes was compared across different cancer types using tissue microarrays (TMAs) composed of up to 50 tumor samples each from 84 different cancer types and subtypes. In total 2652 cancers and 608 normal tissues were successfully analyzed by CD8 immunohistochemistry followed by automated image analysis of digitized slides.

Results

We found that the median CD8⁺ lymphocyte counts ranged from 6 cells/mm² in pleomorphic adenoma up to 1573 cells/mm² in Hodgkin’s lymphoma. The CD8 counts were generally lower in normal tissues compared to cancer tissues. Blood vessels of the spleen were the only non-lymphatic tissue staining positive for CD8. Tumor types approved for checkpoint inhibitor therapy, including malignant melanoma (81), muscle invasive urothelial carcinoma (119), small cell lung cancer (120), clear cell renal cell cancer (153), squamous cell carcinoma (189) and adenocarcinoma of the lung (328) as well as Hodgkin’s lymphoma (1573) were all ranking among the upper half of our list. Comparably high CD8 densities (median cells/mm²) were also found in several rare and aggressive cancer types including Merkel cell carcinoma (70), angiosarcoma (95), anaplastic thyroid cancer (156) and embryonal carcinoma of the testis (186). In 73 of the 84 analyzed cancer types, the highly variable CD8 counts occasionally exceeded the average CD8 count of tumors for which checkpoint inhibitors have been approved.

Conclusion

These data support the concept that among most tumor types at least some individual cancers may benefit from treatment with immune checkpoint inhibitors.

中文翻译：

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人类肿瘤中 CD8+ 细胞毒性淋巴细胞的患病率。

目的

免疫检查点抑制剂最近已被美国 FDA 批准作为部分癌症类型的一线和/或二线疗法。最近的证据表明，肿瘤浸润淋巴细胞 (TIL) 的数量会影响对免疫检查点抑制剂产生反应的可能性。在这里，我们着手评估多种不同癌症类型和亚型中CD8 ^{+淋巴细胞的密度。}

方法

使用组织微阵列 (TMA) 比较不同癌症类型的CD8 ⁺淋巴细胞密度，该组织微阵列由多达 50 个肿瘤样本组成，每个样本来自 84 种不同的癌症类型和亚型。通过 CD8 免疫组织化学成功分析了总共 2652 种癌症和 608 种正常组织，随后对数字化切片进行了自动图像分析。

结果

我们发现CD8 ⁺淋巴细胞计数中位数范围从多形性腺瘤中的6 个细胞/mm ²到霍奇金淋巴瘤中的1573 个细胞/mm ^{2 。}与癌组织相比，正常组织中的 CD8 计数通常较低。脾脏血管是唯一 CD8 染色呈阳性的非淋巴组织。批准用于检查点抑制剂治疗的肿瘤类型，包括恶性黑色素瘤（81）、肌肉浸润性尿路上皮癌（119）、小细胞肺癌（120）、透明细胞肾细胞癌（153）、鳞状细胞癌（189）和腺癌肺癌（328）和霍奇金淋巴瘤（1573）都排在我们名单的上半部分。在几种罕见的侵袭性癌症类型中也发现了相对较高的 CD8 密度（中位细胞/mm ²），包括默克尔细胞癌 (70)、血管肉瘤 (95)、甲状腺未变性癌 (156) 和睾丸胚胎癌 (186)。在分析的 84 种癌症类型中，有 73 种的高度变异的 CD8 计数偶尔超过已批准检查点抑制剂的肿瘤的平均 CD8 计数。

结论

这些数据支持这样的概念：在大多数肿瘤类型中，至少某些个体癌症可能受益于免疫检查点抑制剂的治疗。