Tumours can act as adjuvants for humoral immunity.
Tumour cells transfected with cDNAs encoding non-self proteins were used to investigate the ability of the immune system to respond to immunogenic antigens expressed by tumours. Secreted, intracellular and surface proteins were used as model antigens, as these reflect the potential forms of tumour antigens. Syngeneic BALB/c mice injected with viable line 1 lung carcinoma or EMT6 mammary tumour cells secreting ovalbumin (OVA) or prostate-specific antigen (PSA) produced very high immunoglobulin G (IgG) antibody titres, equivalent to those of mice injected with protein in Freund's complete adjuvant (FCA). Secretion of the antigens was not necessary as tumour cells expressing a cell-surface antigen (HER-2/Neu) or an intracellular antigen - green fluorescence protein (GFP) - also generated high-titre antigen-specific IgG antibodies. In interleukin-4 (IL-4)-deficient mice, both IgG1 and IgG2a were produced in response to OVA administered in FCA, whereas in response to tumour-produced antigen, the antibodies switched from predominantly IgG1 to IgG2a, indicating that the mechanisms responsible for antibody induction differed between these forms of immunization. In contrast to the line 1 and EMT6 tumours, which are of BALB/c origin, OVA- or PSA-producing B16 melanoma cells, which are of C57BL/6 origin, failed to elicit antibody production. This was not the result of strain differences, as a similar finding was observed when the tumours were grown in (BALB/c x C57BL/6)F1 mice, but appeared to be caused by intrinsic differences in the tumours. Furthermore, co-injection of both B16/OVA and line 1 tumours resulted in production of anti-OVA antibody, indicating that B16 tumours were not immunosuppressive, but instead line 1 tumours appear to exert an adjuvant effect.
Brown
D M
DM
Department of Microbiology & Immunology, University of Rochester Medical Center, Rochester, NY, USA.
Fisher
T L
TL
Wei
C
C
Frelinger
J G
JG
Lord
E M
EM
D000276:Adjuvants, Immunologic; D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis*; D000951:Antigens, Neoplasm / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D015847:Interleukin-4 / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000276:immunology; D008545:Melanoma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D007074:Immunoglobulin G; D015847:Interleukin-4; D010047:Ovalbumin