Effect of Hyperthermia on the Immuñoco mpete nee of VX2 Tumor-bearing Rabbits1

Nonspecific ¡mmunocompetencein 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 15to 20-ml i.m. VX2 tumor in the hind limb were treated by local and total-body heating after established métastaseswere present in regional and aor tic lymph nodes and lungs. Following local heating of the VX2 (intratumor tempera ture, 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 x 10" VX2 cells; 1 x 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 de crease 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 radiofre quency treatment. In 7 of the animals (88%), temporary restraint of tumor growth was followed by return to expo nential 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 dinitrochloroben zene and tumor extract and in serum levels of antitumor and anti-bovine serum albumin antibody. Necrotic material removed from regressing VX2 carci nomas up to 17 days after radiofrequency heating pro duced 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 métastases.The abrogation of such enhanced immunocompetence by total-body heating sup1 Work was supported by the North of England Council of the Cancer Research Campaign. Received January 18, 1978; accepted July 11, 1978. ports the concept that in this animal tumor system wholebody hyperthermia is hazardous for the host.