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1.
Cancer Immunol Immunother ; 60(1): 123-31, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20960187

ABSTRACT

The use of whole cell tumor vaccines and various means of loading antigen onto dendritic cells have been under investigation for over a decade. Induction of apoptosis and the exposure of immune-stimulating proteins are thought to be beneficial for the use in immunotherapy protocols, but conclusive evidence in the clinical setting has been lacking. Incubation of melanoma cell lines with interferon-gamma (IFN-γ) increased phosphatidylserine and calreticulin exposure, but not in the IFN-γ-resistant cell line Lu-1205. Short-term autologous melanoma cell lines used for loading dendritic cells for immunotherapy showed differential response to the pro-apoptotic effects of IFN-γ. These IFN-γ-treated tumor cells (TCs) were irradiated and used for loading antigen for dendritic cell therapy. A log-rank comparison of survival for patients whose TCs were found to be either sensitive (upregulated phosphatidylserine and calreticulin) or insensitive to IFN-γ revealed a strongly significant correlation to progression-free (p = 0.003) and overall survival (p = 0.002) favorably in those patients whose cell lines were resistant to the proapoptotic effect of IFN-γ. These results suggest that the use of IFN-γ in anti-melanoma dendritic cell-based immunotherapy may only be beneficial when the cells do not undergo apoptosis in response to IFN-γ and support the contention that the use of some apoptotic cells in vaccines may be detrimental.


Subject(s)
Dendritic Cells/drug effects , Immunotherapy, Adoptive , Melanoma/therapy , Skin Neoplasms/therapy , Adult , Aged , Antigens, Neoplasm/immunology , Antigens, Neoplasm/metabolism , Apoptosis/drug effects , Calreticulin/genetics , Calreticulin/metabolism , Cell Line, Tumor , Dendritic Cells/immunology , Dendritic Cells/metabolism , Dendritic Cells/pathology , Disease-Free Survival , Drug Resistance , Female , Humans , Interferon-gamma/pharmacology , Male , Melanoma/immunology , Melanoma/mortality , Melanoma/pathology , Middle Aged , Phosphatidylserines/genetics , Phosphatidylserines/metabolism , Skin Neoplasms/immunology , Skin Neoplasms/mortality , Skin Neoplasms/pathology
5.
Lancet ; 343(8899): 735, 1994 Mar 19.
Article in English | MEDLINE | ID: mdl-7907706
6.
J R Coll Physicians Lond ; 25(3): 270, 1991 Jul.
Article in English | MEDLINE | ID: mdl-30667882
8.
BMJ ; 297(6648): 625, 1988 Sep 03.
Article in English | MEDLINE | ID: mdl-3139257
9.
Ann R Coll Surg Engl ; 69(3): 146-7, 1987 May.
Article in English | MEDLINE | ID: mdl-3606006
10.
Br Med J (Clin Res Ed) ; 291(6495): 602, 1985 Aug 31.
Article in English | MEDLINE | ID: mdl-3929887
13.
Br Med J ; 2(6197): 1073, 1979 Oct 27.
Article in English | MEDLINE | ID: mdl-519290
14.
Br Med J ; 2(6188): 500-1, 1979 Aug 25.
Article in English | MEDLINE | ID: mdl-487034
15.
Br Med J ; 2(6183): 207, 1979 Jul 21.
Article in English | MEDLINE | ID: mdl-466353
16.
Lancet ; 2(8096): 949-50, 1978 Oct 28.
Article in English | MEDLINE | ID: mdl-81970
17.
Br Med J ; 2(6103): 1671-2, 1977.
Article in English | MEDLINE | ID: mdl-589411
18.
Br Med J ; 2(6096): 1223, 1977 Nov 05.
Article in English | MEDLINE | ID: mdl-589106
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