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

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. Synergisme Entre l'Immunite Antitumorale de l'Hote et un Traitement Combinant Diveres Modalites Contre le Cancer Mammaire Murin L'etat immunitaire specifique de la tumeur des souris proteuses de transplants primaires de tumeurs mammaires syngeniques spontanees a ete controle in vitro avant, pendant et apres un traitement comprenant une enucleation chirurgicale de la tumer plus une premiere serie d'injection d'une combinaison d'agents chimiotherapiques, qui a donne un nombre considerable de guerisons avie dans des cas d'adenocarciome mammaire spontanement apparu chez cet homurin. L'immunite a mediation cellulaire, qui n'etait plus decelable en presence de grosses tumeurs, est reapparue dans les 8 jours suivant l'enucleation. De plus, l'activite de blocage specifique de la tumeur decelable dans le serum des souris concereuses a disparu dans les se 15 jours suivant l'enucleation. Neanmoins, cette evolution favorable de l'etat immunitaire a la suite de l'interventionchirugicale ne suffit pas a empecher la recurrence des tumeurs apartir de microfoyers de cellules tumorales ayant subsiste apres l'enucleation. Par contre, la recurrence a ete sensiblementj inhbee chez les animaux qui ont recu une serie complementaire d'injections dans le cadre de la chimiotherapie combinee intermittents. Les resultats des etudes immunologiques montrent que le succes curatif de cette thesultas des etudes immunologiques montrent que le succes curatif de cette therapeutique depend d'une complementarite, dans l'activite antitumorale, entre le traitement combine et l'immunite de l'ho;te, Un fait d'unej importance primodiale est que le systeme de chimiotherapie n'a produit aucune suppression mesurable de l'immumite specifique de la tumeur et n'a pas interfere avec les modifications favorables de l'equilibre ente les reactions immunologiques qui ont suivi la reduction chirurgicale de la tumeur. En outre, l'administration repetee des produits chimiques sert a la disparition de l'activite de blocage serique. De ce fait, le nombre de cellules tumorales est encore relativement faible lorsque la reaction immunologique efferente favorise au maximum le rejet des cellules tumorales.