caa a22 4500 469073926 CHVBK 20180323132929.0 cr unu---uuuuu 170328e19920901xx s 000 0 eng 10.1007/BF01741149 doi (NATIONALLICENCE)springer-10.1007/BF01741149 Tumorigenicity of interleukin-2 (IL-2)-cDNA-transfected L1210 lymphoma and its in vivo variants is modulated by changes in IL-2 expression; potential therapeutic implications [Elektronische Daten] [Prabir Chakravarty, Hiroshi Fuji, Mahmoud Abu-hadid, Shih-Chung Hsu, Ashwani Sood] Summary: To study parameters that affect the tumorigenicity of L1210 lymphoma we have analyzed the structure of MHC class I antigens of this tumor. In addition this tumor was transfected with interleukin-2 (IL-2) cDNA in order to determine the effects of high concentrations of IL-2 within the tumor environment. The nucleotide sequence of the class I Kd, Dd and Ld mRNAs from this tumor showed that the encoded amino acid sequence of the corresponding antigens is normal, thus suggesting that the tumorigenicity of L1210 lymphoma is not due to defective antigen presentation to tumor-specific cytotoxic T cells. In contrast, induction of IL-2 expression by cDNA transfection led to loss of tumorigenicity of the IL-2-secreting tumor cells. However, a fraction of long-term-surviving mice developed progressively growing variant tumors that showed substantial decrease or loss of IL-2 expression. These results suggest that IL-2 secretion by tumors is suicidal but, because of tumor heterogeneity, IL-2-loss-variant tumors may arise that are able to escape the immune defenses of the host. The observed consistent loss of IL-2 expression in variant tumors implies that specific targeting of large quantities of IL-2 to tumor cells may be a valuable approach to immunotherapy of cancer. In addition we find that under specific gamma ray irradiation IL-2-secreting tumor cells lose their ability to multiply yet continue to secrete IL-2 at levels equivalent to those secreted by unirradiated cells. Such IL-2-secreting irradiated tumor cells were found to be superior immunogens in comparison to the irradiated parental tumor cells, suggesting their use as tumor vaccines. Springer-Verlag, 1992 Major histocompatibility antigens nationallicence IL-2 expression nationallicence Tumorigenicity nationallicence In vivo variants nationallicence Tumor vaccine nationallicence Chakravarty Prabir Department of Molecular Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263, Buffalo, NY, USA aut Fuji Hiroshi Department of Molecular Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263, Buffalo, NY, USA aut Abu-hadid Mahmoud Department of Molecular Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263, Buffalo, NY, USA aut Hsu Shih-Chung Department of Molecular Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263, Buffalo, NY, USA aut Sood Ashwani Department of Molecular Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263, Buffalo, NY, USA aut Cancer Immunology, Immunotherapy Springer-Verlag 35/5(1992-09-01), 347-354 0340-7004 35:5<347 1992 35 262 https://doi.org/10.1007/BF01741149 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01741149 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chakravarty Prabir Department of Molecular Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263, Buffalo, NY, USA aut NATIONALLICENCE 700 1- Fuji Hiroshi Department of Molecular Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263, Buffalo, NY, USA aut NATIONALLICENCE 700 1- Abu-hadid Mahmoud Department of Molecular Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263, Buffalo, NY, USA aut NATIONALLICENCE 700 1- Hsu Shih-Chung Department of Molecular Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263, Buffalo, NY, USA aut NATIONALLICENCE 700 1- Sood Ashwani Department of Molecular Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263, Buffalo, NY, USA aut NATIONALLICENCE 773 0- Cancer Immunology, Immunotherapy Springer-Verlag 35/5(1992-09-01), 347-354 0340-7004 35:5<347 1992 35 262 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer