Limitations of bystander killing in Th1/M1 immune responses against a secreted tumor antigen

T-cell recognition of tumor antigens presented on tumor-infiltrating macrophages (TAMs) induces a tumoricidal M1-like phenotype. Resultant indirect immune responses could eliminate not only antigen secreting (Ag-POS), but also antigen negative (Ag-NEG) tumor cells via bystander killing. Such broad-spectrum response could eliminate antigenically heterogeneous tumors. Using an in vivo model of CD4(+) T-cell mediated immunity against MHC II negative myeloma cells, bystander killing of Ag-NEG cells was ineffective due to strict spatial constraints of Th1-induced TAM cytotoxicity.