Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Head & Neck Surgery, Peking University Cancer Hospital & Institute, Beijing, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing, China.
Front Immunol. 2022 Jun 3;13:821601. doi: 10.3389/fimmu.2022.821601. eCollection 2022.
The intratumor heterogeneity (ITH) of the amount and TCR repertoires of tumor infiltrating lymphocytes (TILs) in PTC with and without coexistent Hashimoto's thyroiditis (HT) are unclear. Here, we investigated the amount of T cells in tumor and corresponding normal tissues by immunohistochemical staining on 80 tumor samples and 40 normal samples from 40 patients. The immune repertoire of T cells was identified on 24 tumor samples and 12 normal samples from 12 patients using TCR high-throughput sequencing. The results demonstrated that the numbers of CD3+, CD4+ and CD8+ T cells in PTC without coexistent HT (PTC-WO) were significantly lower than those in PTC with existing HT (PTC-W). In PTC-W, the density of CD4+ TILs were generally higher when compared with CD8+ TILs. Furthermore, we found that the numbers of CD3+ T cells and their CD4+, CD8+ subtypes in tumor samples were generally higher than those in normal tissue in PTC-WO and moreover, the number of CD3+ T cells was negatively associated with TCR clonality in PTC-WO. In addition, although ITH of the TCR repertoire truly existed in PTC-W and PTC-WO, the TCR repertoires between distinct regions of the non-adjacent tumor foci were presented with a higher degree of similarity than those between tumor and matched normal tissue in PTC-WO, yet the similarity of intratumor repertoires was not significantly higher than those between tumor and corresponding normal samples in PTC-W. This research comprehensively delineated the quantity and TCR repertoire ITH of T cells in PTC-W and PTC-WO, suggesting that TILs might be reactive to tumor antigens in PTC-WO. Moreover, multiregion biopsies should be performed to precisely identify the immune background in PTC-W and PTC-WO.
甲状腺乳头状癌（PTC）伴或不伴桥本甲状腺炎（HT）肿瘤内浸润淋巴细胞（TIL）数量和 TCR 谱的肿瘤内异质性（ITH）尚不清楚。本研究通过免疫组化染色对 40 例患者的 80 例肿瘤样本和 40 例正常样本中的 T 细胞数量进行了检测，通过 TCR 高通量测序对 12 例患者的 24 例肿瘤样本和 12 例正常样本中的 T 细胞免疫谱进行了检测。结果表明，不伴 HT 的 PTC（PTC-WO）中 CD3+、CD4+和 CD8+T 细胞数量明显低于伴 HT 的 PTC（PTC-W）。在 PTC-W 中，CD4+TIL 的密度通常高于 CD8+TIL。此外，我们发现 PTC-WO 中肿瘤样本中 CD3+T 细胞及其 CD4+、CD8+亚群的数量通常高于正常组织，而且 CD3+T 细胞的数量与 PTC-WO 中 TCR 克隆性呈负相关。此外，尽管 PTC-W 和 PTC-WO 中确实存在 TCR 谱的 ITH，但非相邻肿瘤灶不同区域之间的 TCR 谱具有更高的相似性，而 PTC-WO 中肿瘤与匹配正常组织之间的相似性则较低，然而 PTC-W 中肿瘤与相应正常样本之间的相似性并不显著高于肿瘤内的相似性。本研究全面描绘了 PTC-WO 和 PTC-W 中 T 细胞数量和 TCR 谱的 ITH，提示 TIL 可能对 PTC-WO 中的肿瘤抗原有反应。此外，应该进行多区域活检，以准确识别 PTC-W 和 PTC-WO 的免疫背景。
