EblacZ tumor dormancy in bone marrow and lymph nodes: Active control of proliferating tumor cells by CD8(+) immune T cells

A well-defined lacZ gene tagged DBA/2 lymphoma (EblacZ) was used to examine the role of host immune responses in controlling tumor dissemination and p ersistence, as well as metastasis, In s.c. and intra-ear pinna-inoculated m ice, low numbers of EblacZ cells homed to the bone marrow and lymph nodes. The frequency of bone marrow-residing tumor cells did not change with the g rowth of primary tumor or with multiple inoculations of tumor cells. The bo ne marrow-residing tumor cells expressed the proliferation-associated Ki67 antigen and expanded upon CD8(+) depletion. In contrast, inoculation of nu/ nu or severe combined immunodeficiency mice or of immune-suppressed DBA/2 m ice led to the rapid outgrowth of EblacZ cells in the bone marrow and their metastasis to other organs. Transfer of bone marrow from EblacZ immunized MHC congenic or syngeneic DBA /2 donors, but not from naive donors, protected s.c.-inoculated DBA/2 mice. Protection was abrogated by in vitro depletion of CD8(+) T cells prior to transfer of bone marrow. These experiments show that bone marrow and lymph nodes are privileged sites where potentially lethal tumor cells are control led in a dormant state by the immune system. Metastasis may be a consequenc e of the breakdown of this immune control.