Identification of a lung cancer antigen evading CTL attack due to loss of human leukocyte antigen (HLA) class I expression

Cancer Science
Tetsuro BabaKosei Yasumoto

Abstract

The human lung cancer cell line, C831L, lost HLA class I expression due to a mutation of the β2-microglobulin (β2m) gene, and it may have been the result of immunoediting by CTL cytotoxicity. By restoration of HLA class I expression, we could identify the antigen that may be associated with HLA downregulation. Such an antigen might be a promising target of immunotherapy because it potentially may induce a sufficient immune response to eradicate cancer cells. The CTL clone could be established from lymph node lymphocytes in patient C831 by stimulation with wild-type β2m-transduced C831L (C831L-wβ2m). The CTL clone showed reactivity against C831L-wβ2m in a HLA-B*0702-restricted manner, but not Parental-C831L or autologous normal cells. The cDNA expression cloning method was used to identify the antigen coding gene recognized by the CTL clone. The cDNA clone exhibited a homology with a part of the mRNA that codes for leucine rich repeat containing eight family member A (LRRC8A). A transfection analysis of minigenes indicated that the antigen peptide was derived from protein translated from the downstream of the registered open reading frame in LRRC8A mRNA. The antigenic 9-mer peptide (GPRESRPPA) was identified. The present methodo...Continue Reading

References

Jan 1, 1994·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·B PasslickK Pantel
Oct 31, 2002·Nature Immunology·Gavin P DunnRobert D Schreiber
Oct 31, 2002·Nature Immunology·Hung T Khong, Nicholas P Restifo
Dec 9, 2003·The Journal of Clinical Investigation·Akihisa SawadaJunichi Hara
Apr 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yoshinobu IchikiKosei Yasumoto
Sep 2, 2004·Nature Medicine·Steven A RosenbergNicholas P Restifo
Sep 29, 2004·Proceedings of the National Academy of Sciences of the United States of America·Christophe LonchayThierry Boon
Nov 9, 2004·Trends in Immunology·Lorenzo MorettaAlessandro Moretta
Apr 1, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mark E DudleySteven A Rosenberg
Jul 22, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yoshika NagataKosei Yasumoto
Nov 16, 2005·International Journal of Cancer. Journal International Du Cancer·Mitsuhiro TakenoyamaPierre G Coulie
Dec 31, 2005·Nucleic Acids Research·Martin MokrejsMartin Pospísek
Jul 1, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric J SmallRobert M Hershberg
Nov 30, 2006·International Journal of Cancer. Journal International Du Cancer·Masakazu SugayaKosei Yasumoto
Jan 24, 2007·CA: a Cancer Journal for Clinicians·Ahmedin JemalMichael J Thun
Feb 24, 2007·Molecular & Cellular Proteomics : MCP·Masaaki OyamaSumio Sugano

❮ Previous
Next ❯

Citations

Feb 9, 2012·Tissue Antigens·A B del CampoF Garrido
Jun 21, 2013·International Journal of Cancer. Journal International Du Cancer·Ana B del CampoNatalia Aptsiauri
Jul 5, 2013·International Journal of Cancer. Journal International Du Cancer·Osmel CompanioniCarlos A González
Nov 9, 2014·Journal of Cancer Research and Clinical Oncology·Ke LiJunnian Zheng

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antigenic Modulation

Antigenic modulation occurs when an antibody cross-links antigens on a cell surface, causing the antigens to become internalized. This can lead to therapeutic failure of monoclonal antibodies as the expression of the antigen becomes decreased on target cells. Find the latest research on antigenic modulation here.