Antigenic cancer cells that escape immune destruction are stimulated by host cells

Abstract

Cancers induced by UV light in murine skin often regress completely when transplanted into normal syngeneic recipients and grow progressively only in T-cell-deficient hosts. Heritable cancer variants that grow progressively and kill normal mice occasionally evolve in vivo. It is surprising that most of these variants appear to retain their antigenicity and immunogenicity. We have compared three such variants (4102-PRO, 6132A-PRO, and 6134-PRO) with the parental tumors to determine why the variants acquired progressive phenotypes without antigen loss. We found that all three variants grew substantially faster than the parental tumors in T-cell-deficient hosts; one variant, 6132-PRO, also grew faster in vitro. Furthermore, the growth of all of the variants was stimulated by soluble factors released by tumor-induced peritoneal exudate cells, and all attracted more leukocytes than the parental cells. Finally, pretreatment of mice with antigranulocyte antibody reduced the growth of variant but not parental 4102 and 6134A tumor cells. The treatment reduced the growth of both the parental and the variant 6132A lineage cells. We found no evidence for acquired resistance of variant tumors to immune destruction by a host defense mechanism. The parental cells did not grow faster in beige nude mice deficient in natural killer and alpha beta T cells or in SCID mice deficient in B and T cells. The variant parental cells had a similar sensitivity to lysis by polyinosinic-polycytidic acid-induced natural killer cells or thioglycolate- and LPS-induced macrophages. Together, our results are consistent with the notion that these variants escape from immune destruction in vivo by attracting leukocytes that stimulate tumor cell growth.