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Progressive Growth of Immunogenic Tumors: Relationship between Susceptibility of Ascites P815 Tumor Cells to T-Cell-mediated Lysis and Immune Destruction in Vivo¹

Trudeau Institute, Inc., Saranac Lake, New York 12983

Progressive growth of the P815 mastocytoma as an ascites in either normal or immunodepressed, semisyngeneic B6D2F₁ mice resulted in the outgrowth of tumor cells resistant to lysis in vitro by tumor-specific cytotoxic T-lymphocytes (CTLs). Additional testing in vitro showed that late ascites tumor cells also developed a progressive decline in susceptibility to lysis by alloreactive CTLs. The decline in susceptibility to lysis by tumor-specific CTLs was not the result of the loss of tumor-associated antigens, since late tumor cells had the capacity to inhibit the lysis of early, log-phase growth P815 cells in a cold-target inhibition assay. Further studies showed that later, CTL-resistant tumor cells regained susceptibility to CTL lysis if they were incubated for 24 h in vitro. Studies of susceptibility to in vivo immune mechanisms demonstrated that late tumor cells were as susceptible as early tumor cells to adoptive immunotherapy with spleen cells taken from mice immunized against the early tumors. Taken together, these studies suggest that the resistance of late tumor cells to in vitro lysis by CTLs is a reversible phenomenon that may have no relevance to the expression of antitumor immunity in vivo.

¹ This work was supported by a grant from RJR Nabisco, Inc., a grant from the J. M. Foundation, and by USPHS Grant CA-40597 awarded by the National Cancer Institute.

² Present address: Lederle Laboratories, Department of Viral Vaccine Research and Development, Pearl River, NY 10965.

³ To whom requests for reprints should be addressed.

Received 11/ 4/86. Revised 5/23/87. Accepted 6/22/87.