Abstract
The recurrence rate of lymphoma is very high, and tumor stem cells may be an important mechanism. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) can inhibit antitumor immunity and promote cancer progression, but its role and mechanism in lymphoma are still unclear. Here we collected lymphoma tissue and peripheral blood from patients with diffuse large B-cell lymphoma (DLBCL). Results showed that CTLA-4 expression and CD44+ cell in the high-risk group were significantly higher than that in the low-risk group. Correlation analysis showed that CTLA-4 expression positively correlated with CD44+ cell in lymphoma tissue and regulatory T (Treg) cells in lymphocytes. In vitro experiment showed that CTLA-4 increased the ratio of lymphoma stem cells, and proliferation and invasion of lymphoma cells through TGF-β pathway. Moreover, CTLA-4 enhanced the proliferation of Treg cells induced by lymphoma cells. Animal experiments showed that CTLA-4 can promote transplanted lymphoma growth. Immunohistochemistry results showed that both Ki-67 and CD44+ cells increased significantly in the CTLA-4 group. TGF-β neutralization can significantly block these effects of CTLA-4. In conclusion, CTLA-4 promoted DLBCL progression through lymphoma stem cell enrichment and immunosuppression.
Highlights
Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma
The purpose of this study is to investigate the expression of Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) in DLBCL and to explore its correlation with tumor stem cells and Treg cells, so as to provide theoretical support for immunotherapy of lymphoma
Correlation analysis results showed that CTLA-4 expression was positively correlated with the proportion of CD44+ cells in lymphoma, indicating that CTLA-4 may have a certain correlation with tumor stem cells (Figure 1)
Summary
Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. The symptoms of lymphoma are not clinically specific, so early diagnosis is very difficult [1]. Many patients are in advanced stages when they are diagnosed. Chemotherapy and radiotherapy can achieve temporary remission, the recurrence rate of lymphoma is very high [2]. Clinical research showed that over 40% of DLBCL will recur in months to years after treatment, and it was often difficult to cure after recurrence [3]. It is of great clinical significance to find new targets for the diagnosis and treatment of lymphoma
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