Role of cell-mediated immunity in tumor eradication by hyperthermia

A single hyperthermic treatment (44.5 degrees for 20 min) which results in successful local control of a 7-day intradermally growing fibrosarcoma in intact mice fails to permanently control tumor growth in immunodeficient nu/nu (BALB/c) or immunosuppressed (whole-body radiation, 500 rads) mice. Studies were designed to determine whether humoral or cellular-mediated factors were responsible. Nude mice were reconstituted with either heterozygotic (nu/+) sensitized or nonsensitized splenic T-cells. Similarly, semisyngeneic immunosuppressed BALB/c x C57BL/6 F1 hybrids were reconstituted with homologous sensitized and nonsensitized T-cells or sera prior to hyperthermic treatment of a 7-day intradermal Meth-A implant. Successful local tumor control by hyperthermia was effected in those animals reconstituted with greater than or equal to 1.8 x 10(7) splenic T-cells but not in those with sera. The inhibition of macrophage activity (chronic silica, i.p.) could substitute for whole-body radiation immunosuppression. These studies indicate that a thermally induced tumor cure would appear to be mediated by an activated macrophage-antigen-T-cell interaction which may be dependent on the initial expression of cell-mediated antitumor immunity that may be generated only in response to immunogenic tumors.