Department of General and Visceral Surgery, Friedrich-Alexander-University, 91054 Erlangen, Germany.
Department of Pathology, Friedrich-Alexander-University, 91054 Erlangen, Germany.
Int J Mol Sci. 2022 May 5;23(9):5163. doi: 10.3390/ijms23095163.
Immunotherapy has become increasingly important in the treatment of colorectal cancer (CRC). Currently, CD73, also known as ecto-5'-nucleotidase (NT5E), has gained considerable interest as a potential therapeutic target. CD73 is one of the key enzymes catalyzing the conversion of extracellular ATP into adenosine, which in turn exerts potent immune suppressive effects. However, the role of CD73 expression on various cell types within the CRC tumor microenvironment remains unresolved. The expression of CD73 on various cell types has been described recently, but the role of CD73 on B-cells in CRC remains unclear. Therefore, we analyzed CD73 on B-cells, especially on tumor-infiltrating B-cells, in paired tumor and adjacent normal tissue samples from 62 eligible CRC patients. The highest expression of CD73 on tumor-infiltrating B-cells was identified on class-switched memory B-cells, followed by naive B-cells, whereas no CD73 expression was observed on plasmablasts. Clinicopathological correlation analysis revealed that higher CD73 B-cells infiltration in the CRC tumors was associated with better overall survival. Moreover, metastasized patients showed a significantly decreased number of tumor-infiltrating CD73 B-cells. Finally, neoadjuvant therapy correlated with reduced CD73 B-cell numbers and CD73 expression on B-cells in the CRC tumors. As promising new immune therapies are being developed, the role of CD73 B-cells and their subsets in the development of colorectal cancer should be further explored to find new therapeutic options.
免疫疗法在结直肠癌（CRC）的治疗中变得越来越重要。目前，CD73，也称为外核苷酸酶（NT5E），作为潜在的治疗靶点引起了相当大的关注。CD73 是催化细胞外 ATP 转化为腺苷的关键酶之一，后者反过来发挥强烈的免疫抑制作用。然而，CRC 肿瘤微环境中各种细胞类型上 CD73 的表达作用仍未解决。最近描述了 CD73 在各种细胞类型上的表达，但 CD73 在 CRC 中的 B 细胞上的作用仍不清楚。因此，我们分析了 62 名合格 CRC 患者的配对肿瘤和相邻正常组织样本中 B 细胞上的 CD73，特别是肿瘤浸润 B 细胞上的 CD73。在肿瘤浸润 B 细胞上鉴定出 CD73 的最高表达是在类别转换记忆 B 细胞上，其次是幼稚 B 细胞，而浆母细胞上则没有 CD73 表达。临床病理相关性分析表明，CRC 肿瘤中 CD73 B 细胞浸润较高与总生存率较好相关。此外，转移性患者的肿瘤浸润 CD73 B 细胞数量明显减少。最后，新辅助治疗与 CRC 肿瘤中 CD73 B 细胞数量减少和 B 细胞上的 CD73 表达相关。随着有前途的新免疫疗法的发展，应该进一步探索 CD73 B 细胞及其亚群在结直肠癌发展中的作用，以找到新的治疗选择。
