Rejection of Syngeneic MHC Class I and II-Deficient Tumor Grafts after the Tumor Ulceration: Generation of Long Lived Antitumor Immunity

REMEDI MM, DONADIO AC, VIDES MA

Punta del Este

Congreso; V Congreso Latinoamericano de Inmunología; 1999

Sociedad Latinoamericana de Inmunología

We have developed a mammary tumor cell line obtained from a chemically induced tumor in rats. Previously we have demonstrated that after conditioned medium incubation, these cells up-regulate the expression of MHC class I and II molecules (induced cells). When wild type tumor cells (group 1) or induced cells (group 2) were grafted subcutaneously, they were able to grow and developed a palpable tumor within 6-8 days after tumor challenge. On group 2, we observed a tumor growth rate slower than on group 1. Moreover, most of the tumor on the group 2 showed a regressive behaviour before the 21st day, while on group 1, only a few showed the same behaviour. The regressive behaviour was accompanied with a cellular immune response in 6 of 8 cases studied. In this work, we analyzed the survival of the animals belong to group 1 and group 2. Seven of eight animals from group 2 presented an early cure, and the other died at 22nd day. On group 1 (n=7), one animal died at 24th day and the others were cured but in this case, the regression was later during the control period, alter the tumor ulceration. This ulceration could be the product of the fast tumor growth and the limited irrigation. Sixty days after the graft, cured animals from both groups (n=7) were rechallenged with an equivalent dose of tumor cells on the opposite flank to assay the presence of long-lived antitumor immunity. All rats that previously had rejected tumor were resistant to subsequent tumor challenged. We conclude that defective expresión of MHC molecules in wild type tumor cells might constitute a mechanism by which these cells scape immunologic recognition and lysis by effector cells. Tumor ulceration and tumor cell necrosis could allow phagocytic cells to pick up them, and big quantities of tumor antigen could be presented to T cells. So, a T cell mediated immune response and a long-lived antitumor immunity could be developed.