Synergism between host anti‐tumor immunity and combined modality therapy against murine breast cancer

Abstract

Abstract The tumor‐specific immune status of mice bearing primary transplants of spontaneous syngeneic breast tumors was monitored by in vitro methods before, during and after treatment with a regimen of surgical tumor enucleation plus the first course of a combination of chemotherapeutic agents which has yielded significant numbers of lifetime cures of spontaneous mammary adenocarcinoma in this murine host. Cell‐mediated tumor immunity, which had become undetectable in the presence of large tumors, reappeared within 8 days following enucleative tumor surgery. In addition, tumor‐specific blocking activity which was present in the serum of tumor‐bearing mice became undetectable within 15 days after tumor surgery. Nevertheless, these favorable changes in the immune setting following tumor surgery were not adequate to substantially prevent recurrence of tumors from the microfoci of tumor cells residual to the surgical procedure. In contrast, tumor recurrence was significantly inhibited in animals that received an adjuvant course of intermittent combination chemotherapy. Results of the immunological studies indicate that the curative success of this therapeutic regimen is dependent upon the achievement of a complementation in anti‐tumor activity between the combined modality therapy and host immunity. Of paramount importance is the fact that the schedule of chemotherapy did not produce any measurable suppression of tumor‐specific immunity, and did not interfere with the beneficial shift in the balance between tumorimmune reactivities which followed surgical reduction of the tumor burden. In addition, the repeated administration of the drugs serves to keep down the number of tumor cells during the period of time following surgery which has been shown to correspond with the reappearance of cellular anti‐tumor activity and the disappearance of humoral blocking activity. Consequently, the tumor‐cell number is still relatively low when efferent immunological reactivity is most favorable for tumor‐cell rejection.