The tumor dormant state. Quantitation of L5178Y cells and host immune responses during the establishment and course of dormancy in syngeneic DBA/2 mice

Abstract

Subcutaneous implantation of DBA/2-derived L5178Y cells into DBA/2 mice followed 10 d later by nodule excision protected 100% of mice from the rapid outgrowth of an intraperitoneal challenge of L5178Y cells given 7 d postexcision. Challenged mice remained clinically normal for 48--250 d before onset of an ultimately fatal tumor outgrowth. The numbers of L5178Y cells in the peritoneal cavity increased logarithmically for 4 d after challenge and then declined to low but detectable levels which persisted throughout the clinically normal period. Cells active in 18-h in vitro cytolytic assays against 51Cr-labeled L5178Y target cells were found in the peritoneal cavity. The effector cells were determined to be Thy1.2 positive. Their activity was tumor specific and reached peak levels 4 d after tumor challenge and then gradually declined to undectable levels during the following 70 d. Tumor emergence occurred most frequently during the period when CMC activity was no longer demonstrable in the remaining clinically normal mice. A transient peak of low level cytophilic antitumor antibody was detected about 30 d after tumor cell challenge. The temporal associations between the numbers of tumor cells and the levels of cell-mediated lysis against L5178Y cells indicate the importance of the cell-mediated cytolysis response in limiting initial tumor outgrowth and suggest its role as one of the factors responsible for long-term tumor suppression during tumor dormancy.