Journal
ONCOIMMUNOLOGY
Volume 8, Issue 2, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2018.1546544
Keywords
T cells; Natural killer (NK) cells; epstein barr virus (EBV); human T lymphotropic virus type 1 (HTLV-1); pomalidomide; major histocompatibility complex class I (MHC-I); ICAM-1; CD86; interferon regulatory factor 4 (IRF4); ikaros (IKZF1)
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Funding
- Intramural Research Program of the National Institutes of Health, National Cancer Institute
- CRADA
- NATIONAL CANCER INSTITUTE [ZIASC006737] Funding Source: NIH RePORTER
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Most chronic viruses evade T-cell and natural killer (NK) immunity through downregulation of immune surface markers. Previously we showed that Pomalidomide (Pom) increases surface expression of major histocompatibility complex class I (MHC-I) in Kaposi sarcoma-associated herpesvirus-infected latent and lytic cells and restores ICAM-1 and B7-2 in latent cells. We explored the ability of Pom to increase immune surface marker expression in cells infected by other chronic viruses, including human T-cell leukemia virus type-1 (HTLV-1), Epstein-Barr virus (EBV), human papilloma virus (HPV), Merkel cell polyoma virus (MCV), and human immunodeficiency virus type-1 (HIV-1). Pom increased MHC-1, ICAM-1, and B7-2/CD86 in immortalized T-cell lines productively infected with HTLV-1 and also significantly increased their susceptibility to NK cell-mediated cytotoxicity. Pom enhancement of MHC-I and ICAM-1 in primary cells infected with HTLV-1 was abrogated by knockout of HTLV-1 orf-1. Pom increased expression of ICAM-1, B7-2 and MHC class I polypeptide related sequence A (MICA) surface expression in the EBV-infected Daudi cells and increased their T-cell activation and susceptibility to NK cells. Moreover, Pomincreased expression of certain of these surface markers on Akata, Raji, and EBV lymphoblastic cell lines. The increased expression of immune surface markers in these virus-infected lines was generally associated with a decrease in IRF4 expression. By contrast, Pom treatment of HPV, MCV and HIV-1 infected cells did not increase these immune surface markers. Pom and related drugs may be clinically beneficial for the treatment of HTLV-1 and EBV-induced tumors by rendering infected cellsmore susceptible to both innate and adaptive host immune responses.
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