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Antigenic variation in cancer metastasis: immune escape versus immune control

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Summary

Antigenic variation in cancer metastasis was observed in a syngeneic murine tumor system consisting of a low metastatic parental tumor line (derived from a methylcholanthrene-induced DBA/2 T lymphoma, Eb), a high metastatic spontaneous variant thereof (ESb), and a low metastatic ‘revertant’ from ESb (ESb-M). All three lines expressed tumor-associated transplantation antigens (TATA) which elicited specific T cell-mediated antitumor immune reactions in the host. The strongest host response was elicited upon intradermal inoculation. It could be followed by (a) the infiltration of the locally growing tumor by host cells, such as lymphocytes and macrophages, (b) the establishment of specific systemic antitumor immunity, (c) the generation of immune cells capable of transferring protective antitumor immunity into a normal syngeneic recipient, and (d) the generation of tumor specific cytotoxic T lymphocytes (CTL).

Anti-TATA CTL were used as typing reagents to investigate the stability or variability in the TATA expression by cloned tumor cell lines. Antigenic variability in the TATA expression was seen under various conditions: (a) clone-dependent variation in the sensitivity to anti-TATA CTL lysis upon prolonged growth in tissue culture, (b) qualitative change in the TATA (TATA1 → TATA2) upon successive i.p. transplantation of the parental Eb tumor line and, (c) generation of TATA negative immune escape variants (TATA2 → TATA-) during metastasis formation from a s.c. site.

The relative inefficiency of specific immunization procedures against ESb was found to be due to the effective generation of TATA negative variants by this highly metastatic tumor. The balance between immune control and immune escape could be influenced to the advantage of the host by some means, for instance optimizing the route of antitumor-immune sensitization or by infusion of allogeneic but H-2 identical antitumor-immune T cells. Such immune cells recognized the tumor via minor histocompatibility antigens and thus circumvented the need of TATA recognition. Finally, manipulations at the cell surface of the highly malignant ESb tumor such as those introduced in the ESb-M variant were found to dramatically effect its metastatic potential.

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Schirrmacher, V., Fogel, M., Russmann, E. et al. Antigenic variation in cancer metastasis: immune escape versus immune control. Cancer Metast Rev 1, 241–274 (1982). https://doi.org/10.1007/BF00046830

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