In vivo acquired mechanisms of tumor cells local defense against the host innate immunity effectors: implication in specific antitumor immunity.
As shown earlier, the cells transformed in vitro by several different oncogenes, or spontaneously, during in vivo growth in normal hosts would be gradually replaced by the highly-tumorigenic descendants co-expressing high H2O2-catabolizing and PGE2-releasing activities. Acquisition of (H2O2(CA) + PGE(S)) phenotype provides the cells with local defense mechanisms against the host innate immunity effectors. However, it remained unknown, whether the expression of (H2O2(CA) + PGE(S)) phenotype is implicated in susceptibility of tumor cells expressing tumor-specific transplantation antigens to rejection in immune animals. Here, with the use of SV40 in vitro transformed parental cells, negative in expression (H2O2(CA) + PGE(S)) phenotype, and their in vivo selected descendant tumor cell lines expressing this phenotype, we show that: (1) the rates of in vivo selection of the parental SV40 tumor cells expressing (H2O2(CA) + PGE(S)) phenotype are the same in normal and SV40-immune animals; (2) in vivo selected SV40 tumor cells expressing (H2O2(CA) + PGE(S)) phenotype, although they retain specific immunosensitivity, are 100 times less effectively rejected in SV40-immunized animals, as compared with their in vitro SV40-transformed parental cells. Thus, in vivo acquired immunologically non-specific local mechanisms of tumor cells defense against the host innate immunity effectors, significantly decreases the effectiveness of their specific immunorejection.
Deichman
G
G
Laboratory of Antitumor Immunity, Institute of Carcinogenesis, N.N. Blokchin Cancer Research Center, Russian Academy of Medical Sciences, Moscow. antitum@iki.rssi.ru
Dyakova
N
N
Kashkina
L
L
Matveeva
V
V
Uvarova
E
E
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000276:immunology; D000975:Antioxidants / Q000378:metabolism*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D006224:Cricetinae; D015232:Dinoprostone / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007113:Immunity, Innate; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D010641:Phenotype
D000952:Antigens, Polyomavirus Transforming; D000975:Antioxidants; D006861:Hydrogen Peroxide; D015232:Dinoprostone