The therapeutic significance of concomitant antitumor immunity

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Abstract
I.v. injection of 50 .mu.g bacterial endotoxin can cause complete regression of an established SA1 sarcoma, but not if the tumor is growing in mice that are incapable of generating concomitant immunity because they were made T cell-deficient by thymectomy and .gamma.-radiation (TXB mice). Apparently, endotoxin fails to cause a complete regression of a tumor that is either too large or too small. Only when administered on day 9 of tumor growth, at the time of peak concomitant immunity, did endotoxin cause the tumor to undergo complete regression. Direct evidence that the antitumor effect of endotoxin is dependent on concomitant immunity consisted in the demonstration than an SA1 sarcoma growing in TXB recipients can be primed for endotoxin-induced regression by i.v. infusion of splenic T cells from concomitantly immune donors bearing an endotoxin-susceptible 9-day tumor. Surprisingly, the donor T cells that primed the recipient tumor for endotoxin-induced regression were of the Ly-1+2- phenotype, as evidenced by their susceptibility to treatment with anti-Ly-1 antibody and complement, and their complete resistance to treatment with anti-Ly-2 antibody and complement. They were different from the T cells that cause the regression of smaller tumors in .gamma.-irradiated recipients without the aid of endotoxin. Evidently, the antitumor function of endotoxin depends on its ability to cause intratumor macrophages to acquire and express tumoricidal function, but only after the macrophages were activated by Ly-1+2- tumor-sensitized T cells.