造血干细胞移植后结肠腺瘤中 Th1 和 Th2 CD4 T 细胞谱系浸润均减少。
Both Th1 and Th2 CD4 + T-Cell Lineage Infiltrations Decrease in Post-hematopoietic Stem Cell Transplantation Colon Adenoma.
发表日期:2024 Aug 19
作者:
Yasuo Matsubara, Yasunori Ota, Tamami Denda, Yukihisa Tanaka, Masamichi Isobe, Seiko Kato, Takaaki Konuma, Satoshi Takahashi, Yoshihiro Hirata, Hiroaki Ikematsu, Keisuke Baba, Narikazu Boku
来源:
Cellular & Molecular Immunology
摘要:
随着异基因造血干细胞移植(HSCT)后长期生存率的提高,继发性实体癌(包括结肠癌)的风险也会增加。然而,HSCT 后患者继发实体癌的发病机制仍不清楚。本研究旨在通过评估结肠腺瘤中的浸润性 T 细胞作为腺瘤-癌序列中结肠癌的癌前病变,探讨局部免疫在 HSCT 后患者结肠癌发生中的作用。从 19 例 HSCT 后患者中获取结肠腺瘤样本,通过免疫组织化学对 57 名非 HSCT 参与者进行了分析。对 CD4/T-bet、CD4/GATA3 和 CD4/FoxP3 进行双染色,以评估辅助 T 细胞谱系(分别为 Th1、Th2 和调节性 T 细胞),并对 CD8 T 细胞进行 CD8 染色。腺瘤中浸润性 CD4 T 细胞和 CD8 T 细胞数量存在显着组间差异。然而,HSCT 后腺瘤中 CD4 /T-bet 和 CD4 /GATA3 T 细胞的数量均显着低于非 HSCT 腺瘤(分别为 P = 0.0171 和 0.0009),而在尽管浸润性 CD4 和 CD8 T 细胞的数量,甚至 Treg 细胞计数在 HSCT 后得到充分恢复,但结肠腺瘤中由于抑制激活和分化而导致的 CD4 T 细胞功能障碍可能与HSCT 后患者的结肠癌发生。阐明发病机制将有助于制定针对 HSCT 后患者继发性结肠癌的有效筛查和预防计划。© 2024。作者获得 Springer Science Business Media, LLC(Springer Nature 旗下子公司)的独家许可。
As long-term survival improves after allogeneic hematopoietic stem cell transplantation (HSCT), the risk for secondary solid cancers, including colon cancer, also increases. However, the pathogenesis of secondary solid cancers in post-HSCT patients remains unclear. This study aimed to investigate the involvement of local immunity in colon carcinogenesis in post-HSCT patients by assessing the infiltrating T cells in colon adenomas as premalignant lesions of colon cancer in adenoma-carcinoma sequence.Colon adenoma samples obtained from 19 post-HSCT patients and 57 non-HSCT participants were analyzed via immunohistochemistry. Double staining of CD4/T-bet, CD4/GATA3, and CD4/FoxP3 was performed for evaluation of helper T-cell lineages (Th1, Th2, and regulatory T cells, respectively) and CD8 staining for CD8+ T cells.There were no significant between-group differences in the number of infiltrating CD4+ T cells and CD8+ T cells in adenomas. However, the number of both CD4+/T-bet+ and CD4+/GATA3+ T cells was significantly lower in the post-HSCT adenomas than in the non-HSCT adenomas (P = 0.0171 and 0.0009, respectively), whereas no significant differences were found in the number of CD4+/FoxP3+ cells.Although the number of infiltrating CD4+ and CD8+ T cells, and even Treg cell counts, is sufficiently recovered post-HSCT, CD4+ T-cell dysfunction due to suppressed activation and differentiation in colon adenomas might be involved in colon carcinogenesis in post-HSCT patients. Elucidating the pathogenesis will contribute to the development of effective screening and prevention programs for secondary colon cancer in post-HSCT patients.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.