Spontaneous mammary carcinomas fail to induce an immune response in syngeneic FVBN202 neu transgenic mice

FVBN202 mice, which are transgenic for the rat neu gene, spontaneously deve lop mammary carcinomas between 6 and 7 months of age. We investigated wheth er these spontaneous tumors (spontaneous breast carcinoma cells, SBCC) coul d elicit an immune response in naive 6- to 8-week-old FVBN202 transgenic an d FVBN nontransgenic mice. After s.c. injection of SBCC, the recently activ ated T cells, which were identified by their reduced expression of CD62L (L -selectin), were isolated from the draining lymph nodes, expanded with anti -CD3 and IL-2, and their cytokine response to tumor cells in vitro was anal yzed. Tumor-vaccine draining lymph node lymphocytes (TVDLN) from transgenic mice failed to make IFN-gamma in response to the tumor cells. However, TVD LN from the nontransgenic mice exhibited a tumor-specific IFN-gamma respons e against the SBCC, This indicates that the SBCC are immunogenic. The lack of response in transgenic mice could not be attributed to cytokine immune d eviation or T-cell signaling defects. Although transgenic mice were toleran t to their own tumors, their immune competence was established by their abi lity to respond in an allogeneic mixed lymphocyte reaction, to reject an al logeneic breast carcinoma cell line. and to produce a tumor-specific IFN-ga mma response against a syngeneic cancer cell line, This transgenic mouse mo del provides the opportunity to investigate the immune response against a p rimary tumor cell culture rather than cell lines or clones and should prove useful for developing immunotherapies that overcome tolerance to self-tumo r antigens, (C) 2000 Wiley-Liss, Inc.