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Downregulation and/or release of NKG2D ligands as immune evasion strategy of human neuroblastoma.
Neoplasia. 2004 Sep-Oct; 6(5):558-68.N

Abstract

Neuroblastoma (NB) is a pediatric extracranial tumor characterized by downregulation of human leukocyte antigen class I and defects of the antigen processing machinery, two features that make it an appropriate target for natural killer (NK)-mediated lysis. NKG2D is an activating immunoreceptor expressed by cytotoxic T lymphocytes and NK cells. The ligands for NKG2D are the major histocompatibility complex class I-related chain (MIC)A and MICB glycoproteins, and the UL-16-binding proteins (ULBPs). Here, the expression of NKG2D ligands was investigated in human primary NB tumors and cell lines because scanty information is available on this issue. MICA, MICB, and ULBP transcripts were found in most tumors and cell lines. MICA protein was detected in some NB cell lines but not in primary tumors. A soluble form of MICA (sMICA) was identified in most patient sera and in some cell line supernatants. sMICA downregulated surface NKG2D in normal peripheral blood CD8(+) cells and decreased NK-mediated killing of MICA(+) NB cells. MICB was detected exclusively in the cytosol of primary tumors and cell lines. Approximately 50% of primary tumors expressed ULBP-2, but not ULBP-1 or -3. ULBP-3 was expressed in 5 of 9 cell lines, ULBP-2 in 2 of 9, whereas ULBP-1 was never detected. These studies delineate novel potential pathways of tumor escape and immunodeficiency in NB.

Authors+Show Affiliations

Laboratory of Oncology, G. Gaslini Institute, Genova, Italy. lizziaraffaghello@ospedale-gaslini.geNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15548365

Citation

Raffaghello, Lizzia, et al. "Downregulation And/or Release of NKG2D Ligands as Immune Evasion Strategy of Human Neuroblastoma." Neoplasia (New York, N.Y.), vol. 6, no. 5, 2004, pp. 558-68.
Raffaghello L, Prigione I, Airoldi I, et al. Downregulation and/or release of NKG2D ligands as immune evasion strategy of human neuroblastoma. Neoplasia. 2004;6(5):558-68.
Raffaghello, L., Prigione, I., Airoldi, I., Camoriano, M., Levreri, I., Gambini, C., Pende, D., Steinle, A., Ferrone, S., & Pistoia, V. (2004). Downregulation and/or release of NKG2D ligands as immune evasion strategy of human neuroblastoma. Neoplasia (New York, N.Y.), 6(5), 558-68.
Raffaghello L, et al. Downregulation And/or Release of NKG2D Ligands as Immune Evasion Strategy of Human Neuroblastoma. Neoplasia. 2004;6(5):558-68. PubMed PMID: 15548365.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Downregulation and/or release of NKG2D ligands as immune evasion strategy of human neuroblastoma. AU - Raffaghello,Lizzia, AU - Prigione,Ignazia, AU - Airoldi,Irma, AU - Camoriano,Marta, AU - Levreri,Isabella, AU - Gambini,Claudio, AU - Pende,Daniela, AU - Steinle,Alexander, AU - Ferrone,Soldano, AU - Pistoia,Vito, PY - 2004/11/19/pubmed PY - 2005/4/22/medline PY - 2004/11/19/entrez SP - 558 EP - 68 JF - Neoplasia (New York, N.Y.) JO - Neoplasia VL - 6 IS - 5 N2 - Neuroblastoma (NB) is a pediatric extracranial tumor characterized by downregulation of human leukocyte antigen class I and defects of the antigen processing machinery, two features that make it an appropriate target for natural killer (NK)-mediated lysis. NKG2D is an activating immunoreceptor expressed by cytotoxic T lymphocytes and NK cells. The ligands for NKG2D are the major histocompatibility complex class I-related chain (MIC)A and MICB glycoproteins, and the UL-16-binding proteins (ULBPs). Here, the expression of NKG2D ligands was investigated in human primary NB tumors and cell lines because scanty information is available on this issue. MICA, MICB, and ULBP transcripts were found in most tumors and cell lines. MICA protein was detected in some NB cell lines but not in primary tumors. A soluble form of MICA (sMICA) was identified in most patient sera and in some cell line supernatants. sMICA downregulated surface NKG2D in normal peripheral blood CD8(+) cells and decreased NK-mediated killing of MICA(+) NB cells. MICB was detected exclusively in the cytosol of primary tumors and cell lines. Approximately 50% of primary tumors expressed ULBP-2, but not ULBP-1 or -3. ULBP-3 was expressed in 5 of 9 cell lines, ULBP-2 in 2 of 9, whereas ULBP-1 was never detected. These studies delineate novel potential pathways of tumor escape and immunodeficiency in NB. SN - 1522-8002 UR - https://www.unboundmedicine.com/medline/citation/15548365/Downregulation_and/or_release_of_NKG2D_ligands_as_immune_evasion_strategy_of_human_neuroblastoma_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/15548365/ DB - PRIME DP - Unbound Medicine ER -