Resistance to Cytotoxic Chemotherapy Is Induced by NK Cells in Non-Hodgkin's Lymphoma Cells

Daeho Cho, Young In Kim, Jae Seung Kang, Eunsil Hahm, Yoolhee Yang, Daejin Kim, Seonghan Kim, Yeong Seok Kim, Daeyoung Hur, Hyunjeong Park, Young Il Hwang, Tae Sung Kim, Wang Jae Lee

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


It is known that B lymphoma cells are sensitive to cytotoxic chemotherapy, but primary or secondary chemoresistance frequently occurs and is the major cause of death in these patients. However, the mechanisms by which lymphoma cells acquire resistance to cytotoxic drugs are not fully understood. Recently, it was reported that B cells secrete immunoglobulin and produce cytokines after interacting with NK cells, thus indicating the importance of NK/B interactions. In this study, we investigated the mechanism of resistance to cytotoxic chemotherapy induced in cocultures of NK cells and Raji cells. Normally, Raji cells are doxorubicin-sensitive, but Raji cells cocultured with NK cells become doxorubicin-resistant. In addition, we detected the upregulation of CD69 and CD70 on Raji cells cocultured with NK cells, suggesting that Raji cells are activated by NK cells. We also found that the resistance of Raji cells to doxorubicin increased when they had been treated with NK cell coculture supernatant. Furthermore, boiled culture supernatant did not inhibit doxorubicin-mediated cell death, indicating that soluble factors are involved. Finally, we confirmed that NK cells produce TNFα, and that doxorubicin-sensitive Raji cells become doxorubicin-resistant after TNFα treatment. Taken together, these results suggest that B lymphoma cell resistance to doxorubicin-mediated cell death is induced by coculture with NK cells, because of TNFα secretion.

Original languageEnglish
Pages (from-to)553-560
Number of pages8
JournalJournal of Clinical Immunology
Issue number5
Publication statusPublished - 2004 Sep
Externally publishedYes


  • NK
  • Raji
  • TNFα
  • chemotherapy
  • doxorubicin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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