Dynamic expression of protective CEACAM1 on melanoma cells during specific immune attack.
An efficient immune response against tumours depends on a well-orchestrated function of integrated components, but is finally exerted by effector tumour-infiltrating lymphocytes (TIL). We have previously reported that homophilic CEACAM1 interactions inhibit the specific killing and interferon-gamma (IFN-gamma) release activities of natural killer cells and TIL. In this study a model for the investigation of melanoma cells surviving long coincubation with antigen-specific TIL is reported. It is demonstrated that the surviving melanoma cells increase their surface CEACAM1 expression, which in turn confers enhanced resistance against fresh TIL. Furthermore, it is shown that this is an active process, driven by specific immune recognition and is at least partially mediated by lymphocyte-derived IFN-gamma. Similar results were observed with antigen-restricted TIL, either autologous or allogeneic, as well as with natural killer cells. The enhanced CEACAM1 expression depends, however, on the presence of IFN-gamma and sharply drops within 48 hr. This may be a mechanism that allows tumour cells to transiently develop a more resistant phenotype upon recognition by specific lymphocytes. Therefore, this work substantiates the melanoma-promoting role of CEACAM1 and marks it as an attractive target for novel immunotherapeutic interventions.
The Ella Institute of Melanoma, Sheba Cancer Research Centre, Sheba Medical Centre, Tel Hashomer, Israel. markel@post.tau.ac.il
Gal
G
Markel
Rachel
R
Seidman
Yifat
Y
Cohen
Michal J
MJ
Besser
Tali Cohen
TC
Sinai
Avraham J
AJ
Treves
Arie
A
Orenstein
Raanan
R
Berger
Jacob
J
Schachter
D000071443:12E7 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002470:Cell Survival / Q000276:immunology; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D003602:Cytotoxicity, Immunologic; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008545:Melanoma / Q000276:immunology*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000276:immunology
D000071443:12E7 Antigen; D015703:Antigens, CD; D000951:Antigens, Neoplasm; C069847:CD66 antigens; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D015789:HLA-A2 Antigen; D011994:Recombinant Proteins; D007371:Interferon-gamma