CTLA-4 promotes lymphoma progression through tumor stem cell enrichment and immunosuppression
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 t...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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De Gruyter
2021-09-01
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| Series: | Open Life Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/biol-2021-0094 |
| _version_ | 1811203777633452032 |
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| author | Chen Yan Li Meng Cao Jian Cai Guohong Li Xiantao Liu Yuejiao Chen Wen |
| author_facet | Chen Yan Li Meng Cao Jian Cai Guohong Li Xiantao Liu Yuejiao Chen Wen |
| author_sort | Chen Yan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T03:00:54Z |
| format | Article |
| id | doaj.art-86871cff5db446d0a4029a83abc1aef7 |
| institution | Directory Open Access Journal |
| issn | 2391-5412 |
| language | English |
| last_indexed | 2024-04-12T03:00:54Z |
| publishDate | 2021-09-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Open Life Sciences |
| spelling | doaj.art-86871cff5db446d0a4029a83abc1aef72022-12-22T03:50:40ZengDe GruyterOpen Life Sciences2391-54122021-09-0116190991910.1515/biol-2021-0094CTLA-4 promotes lymphoma progression through tumor stem cell enrichment and immunosuppressionChen Yan0Li Meng1Cao Jian2Cai Guohong3Li Xiantao4Liu Yuejiao5Chen Wen6Department of Integrated TCM and Western Medicine, Central Hospital of Yiyang City, Yiyang, Hunan, 413200, ChinaDepartment of Pathology, The 8th Medical Center, Chinese PLA General Hospital, Beijing 100091, ChinaDepartment of Integrated TCM and Western Medicine, Central Hospital of Yiyang City, Yiyang, Hunan, 413200, ChinaDepartment of Integrated TCM and Western Medicine, Central Hospital of Yiyang City, Yiyang, Hunan, 413200, ChinaDepartment of Integrated TCM and Western Medicine, Central Hospital of Yiyang City, Yiyang, Hunan, 413200, ChinaDepartment of Pathology, The 8th Medical Center, Chinese PLA General Hospital, Beijing 100091, ChinaDepartment of Pathology, The 8th Medical Center, Chinese PLA General Hospital, Beijing 100091, ChinaThe 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.https://doi.org/10.1515/biol-2021-0094lymphomactla-4regulatory t celltumor stem cell |
| spellingShingle | Chen Yan Li Meng Cao Jian Cai Guohong Li Xiantao Liu Yuejiao Chen Wen CTLA-4 promotes lymphoma progression through tumor stem cell enrichment and immunosuppression Open Life Sciences lymphoma ctla-4 regulatory t cell tumor stem cell |
| title | CTLA-4 promotes lymphoma progression through tumor stem cell enrichment and immunosuppression |
| title_full | CTLA-4 promotes lymphoma progression through tumor stem cell enrichment and immunosuppression |
| title_fullStr | CTLA-4 promotes lymphoma progression through tumor stem cell enrichment and immunosuppression |
| title_full_unstemmed | CTLA-4 promotes lymphoma progression through tumor stem cell enrichment and immunosuppression |
| title_short | CTLA-4 promotes lymphoma progression through tumor stem cell enrichment and immunosuppression |
| title_sort | ctla 4 promotes lymphoma progression through tumor stem cell enrichment and immunosuppression |
| topic | lymphoma ctla-4 regulatory t cell tumor stem cell |
| url | https://doi.org/10.1515/biol-2021-0094 |
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