Effect of hyperthermia on the immunocompetence of VX2 tumor-bearing rabbits.

Abstract

Abstract Nonspecific immunocompetence in VX2 tumor-bearing rabbits was assessed by skin response to dinitrochlorobenzene and development of antibody titer to bovine serum albumin. Skin reactivity to a 3 m KCI extract of the VX2 and antitumor antibody titer were used to monitor host immunocompetence against the tumor. Rabbits bearing a 15- to 20-mi i.m. VX2 tumor in the hind limb were treated by local and total-body heating after established metastases were present in regional and aortic lymph nodes and lungs. Following local heating of the VX2 (intratumor temperature, 47–50°/30 min) achieved by radiofrequency current at 13.56 MHz, there was tumor regression and host cure in 9 of 13 (70%) rabbits. Tumor regression was accompanied by a marked and sustained increase in skin reactivity to both tumor extract and dinitrochlorobenzene, and there was a 100-fold increase in serum levels of antitumor and anti-bovine serum albumin antibody. The animals are alive 2 years after heating and are immune to inoculation of 30 × 106 VX2 cells; 1 × 106 tumor cells led to a 100% death rate in 72 ± 7 (S.D.) days in untreated rabbits. In the 4 rabbits that did not respond to heating, unrestrained tumor growth was accompanied by a progressive decrease in host response to skin tests and antibody titers of 1:10 or less, findings similar to those in untreated tumor-bearing hosts. Eight rabbits were subjected to total-body hyperthermia (42°/60 min on 3 successive days) 7 days after radiofrequency treatment. In 7 of the animals (88%), temporary restraint of tumor growth was followed by return to exponential increase in tumor volume and rapid death. This was accompanied by abrogation of the enhanced cellular and humoral immune responsiveness that followed local heating; in the single animal that was cured there was a sustained increase in skin response to dinitrochlorobenzene and tumor extract and in serum levels of antitumor and anti-bovine serum albumin antibody. Necrotic material removed from regressing VX2 carcinomas up to 17 days after radiofrequency heating produced tumors on inoculation into rabbits. It is concluded that the immune response generated following curative local heating of the VX2 carcinoma is involved in regression of the primary tumor as well as in the destruction of metastases. The abrogation of such enhanced immunocompetence by total-body heating supports the concept that in this animal tumor system whole-body hyperthermia is hazardous for the host.